MONOGRAFÍA DE MEDICAMENTOS

Naproxeno
Aflaxen | Aleve | Aleve Artritis | Alivio del dolor durante todo el día | Alivio durante todo el día | Anaprox | Anaprox DS | EC-Naprosyn | Alivio
prolongado de Midol | Naprelan | Tarjeta de dosis de Naprelan | Naprosyn
Última revisión: 14 de octubre de 2024 - Información sobre el medicamento proporcionada por Elsevier Información sobre el medicamento (
ver detalles ([Link] ) ([Link]
policy)

Descripción

El naproxeno es un fármaco antiinflamatorio no esteroide (AINE) de la clase química del ácido propiónico. Este medicamento posee propiedades
antipiréticas y analgésicas. El naproxeno es un derivado del ácido propiónico relacionado con el ibuprofeno, el ketoprofeno, el flurbiprofeno y el
fenoprofeno. Existen muchas similitudes farmacodinámicas entre estos agentes, que suelen tolerarse mejor que la aspirina o la indometacina.
Todos los AINE, incluido el naproxeno, conllevan un mayor riesgo de efectos adversos gastrointestinales graves, como sangrado, ulceración y
perforación del estómago o los intestinos, y pueden provocar un mayor riesgo de eventos trombóticos cardiovasculares (CV) graves, infarto de
miocardio y accidente cerebrovascular. El etiquetado aprobado por la FDA tanto de los productos de venta libre como de los de venta con receta
enfatiza la dosificación en la dosis efectiva más baja durante el menor tiempo posible, ya que el riesgo de efectos adversos puede aumentar con el
aumento del uso. Una revisión retrospectiva realizada por los Comités Asesores de la FDA de los ensayos de eficacia a corto plazo de naproxeno
de venta sin receta indicó que no se observó un aumento de los eventos cardiovasculares durante los estudios. Sin embargo, es importante
señalar que el riesgo cardiovascular no fue el foco de los estudios y se necesita más información para determinar si existe una relación de causa y
efecto entre el uso de AINE de venta sin receta y los resultados cardiovasculares adversos. El naproxeno está disponible como anión y como sal
sódica; todas las formulaciones liberan naproxeno como fármaco activo. Se ha demostrado que el naproxeno es superior a la ergotamina en el
tratamiento de la migraña. 23558 El naproxeno fue aprobado por la FDA en 1976. En enero de 1994, la FDA otorgó permiso para comercializar
naproxeno en una forma de venta sin receta (por ejemplo, Aleve).

Indicaciones y dosis

† Indicación fuera de etiqueta

Indicaciones y dosis

espondiloartritis anquilosante gota Dolor moderado

artralgia dolor de cabeza Dolor musculoesquelético

bursitis osificación heterotópica † osteoartritis

resfriado común Artritis reumatoide juvenil (ARJ)/artritis pericarditis †

idiopática juvenil (AIJ)
Dolor dental artritis reumatoide
Profilaxis de la migraña menstrual †
dismenorrea tendinitis
migraña †
fiebre uveítis †
Dolor leve

Para el tratamiento de la espondilitis anquilosante , la osteoartritis o la artritis reumatoide.

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

250 o 500 mg por vía oral dos veces al día. Se puede ajustar la dosis según la respuesta clínica. Máximo: 1500 mg/día durante períodos limitados
de hasta 6 meses. 32122 66841

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

275 o 550 mg por vía oral dos veces al día. Se puede ajustar la dosis según la respuesta clínica. Máximo: 1500 mg/día durante períodos limitados
de hasta 6 meses. 32122
Dosis oral (comprimidos de liberación retardada de naproxeno)

Adultos:

375 o 500 mg por vía oral dos veces al día. Se puede ajustar la dosis según la respuesta clínica. Máximo: 1500 mg/día durante períodos limitados
de hasta 6 meses. 32122

Dosis oral (comprimidos de liberación controlada de naproxeno sódico)

Adultos:

750 o 1000 mg por vía oral una vez al día. Se puede ajustar la dosis según la respuesta clínica. Máximo: 1500 mg/día durante períodos limitados.
44091
Para el tratamiento de la artritis reumatoide juvenil (ARJ)/artritis idiopática juvenil (AIJ)

Dosis oral (comprimidos de naproxeno)

Niños y adolescentes de 2 a 17 años y con peso de 50 kg o más:

5 mg/kg/dosis (Máx: 500 mg/dosis) VO dos veces al día. 32122

Dosis oral (suspensión de naproxeno)

Niños y adolescentes de 2 a 17 años:

5 mg/kg/dosis (Máx: 500 mg/dosis) VO dos veces al día. 66841

Para el tratamiento de la gota aguda

NOTA: El naproxeno de liberación retardada no se recomienda para el tratamiento de la gota aguda debido al retraso en la absorción en
comparación con otras formulaciones de naproxeno. 32122

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

750 mg VO una vez, luego 250 mg VO cada 8 horas según sea necesario hasta que el ataque haya remitido. 32122 64373 66841

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

825 mg VO una vez, luego 275 mg VO cada 8 horas según sea necesario hasta que el ataque haya remitido. 32122

Dosis oral (comprimidos de liberación controlada de naproxeno)

Adultos:

1.000 a 1.500 mg VO una vez, luego 1.000 mg VO una vez al día según sea necesario hasta que el ataque haya remitido. 44091

Para el tratamiento del dolor leve a moderado , incluidos dolores y molestias menores asociados con artralgia , dolor dental , dolor de cabeza ,
dolor musculoesquelético (incluido el dolor de espalda) y/o resfriado común.

NOTA: El naproxeno de liberación retardada no se recomienda para el tratamiento inicial del dolor porque su absorción se retrasa en
comparación con otras formulaciones de naproxeno. 32122

NOTA: El naproxeno sódico puede ser preferible al naproxeno cuando se necesita un alivio del dolor de inicio rápido. 32122

Para el tratamiento del dolor leve a moderado.

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

500 mg por vía oral una vez, luego 250 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1250 mg/día. 32122 66841

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

550 mg por vía oral una vez, luego 550 mg por vía oral cada 12 horas o 275 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1375
mg el día 1, luego 1100 mg/día. 32122

Dosis oral (comprimidos de liberación controlada de naproxeno sódico)

Adultos:

44091
1.000 o 1.500 mg por vía oral una vez al día. Dosis máxima habitual: 1.000 mg/día. 44091
para el tratamiento de dolores y molestias menores asociados con artralgia, dolor dental, dolor de cabeza, dolor musculoesquelético (incluido el
dolor de espalda) y/o resfriado común

Dosis oral (cápsulas o comprimidos de naproxeno sódico de venta libre)

Adultos:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máx.: 660 mg/día. 45292

Niños y adolescentes de 12 a 17 años:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máx.: 660 mg/día. 45292
Para el tratamiento de la dismenorrea

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

500 mg por vía oral una vez, luego 250 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1250 mg/día. 32122 66841

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

550 mg por vía oral una vez, luego 550 mg por vía oral cada 12 horas o 275 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1375
mg el día 1, luego 1100 mg/día. 32122

Dosis oral (comprimidos de liberación controlada de naproxeno sódico)

Adultos:

1.000 o 1.500 mg por vía oral una vez al día. Dosis máxima habitual: 1.000 mg/día. 44091

Dosis oral (cápsulas o comprimidos de naproxeno sódico de venta libre)

Adultos:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máximo: 660 mg/día. Suspenda su uso si el dolor empeora o dura más
de 10 días. 45292

Niños y adolescentes de 12 a 17 años:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máximo: 660 mg/día. Suspenda su uso si el dolor empeora o dura más
de 10 días. 45292

Para el tratamiento de la fiebre.

Dosis oral (cápsulas o comprimidos de naproxeno sódico de venta libre)

Adultos:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máximo: 660 mg/día. Suspenda su uso si la fiebre empeora o dura más
de 3 días. 45292

Niños y adolescentes de 12 a 17 años:

440 mg por vía oral una vez, luego 220 mg por vía oral cada 8 a 12 horas. Máximo: 660 mg/día. Suspenda su uso si la fiebre empeora o dura más
de 3 días. 45292

Para el tratamiento de bursitis y tendinitis.

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

500 mg por vía oral una vez, luego 250 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1250 mg/día. 32122 66841

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

550 mg por vía oral una vez, luego 550 mg por vía oral cada 12 horas o 275 mg por vía oral cada 6 a 8 horas según sea necesario. Máximo: 1375
mg el día 1, luego 1100 mg/día. 32122

Dosis oral (comprimidos de liberación controlada de naproxeno sódico)

Adultos:

1.000 o 1.500 mg por vía oral una vez al día. Dosis máxima habitual: 1.000 mg/día. 44091
Para el tratamiento agudo de la migraña †

Dosis oral (naproxeno)

Adultos:

500 mg por vía oral en dosis única. Las guías clínicas clasifican al naproxeno como un fármaco de eficacia demostrada para el tratamiento de la
migraña aguda. 64565 69288

Dosis oral (naproxeno sódico)

Adultos:

550 mg por vía oral en dosis única. Las guías clínicas clasifican al naproxeno como un fármaco de eficacia demostrada para el tratamiento de la
migraña aguda. 64565 69288

Para la profilaxis de la migraña menstrual †

Dosis oral (comprimidos de naproxeno sódico)

Adultos:

500 o 550 mg VO una o dos veces al día durante 6 días comenzando 2 a 7 días antes del inicio esperado de la menstruación y repitiéndose
mensualmente con cada ciclo menstrual. 58995

Para la prevención de la osificación heterotópica †

Dosis oral (comprimidos de naproxeno o suspensión oral)

Adultos:

250 mg VO 3 veces al día durante 6 semanas o 500 mg VO dos veces al día durante 7 días después de la artroplastia total de cadera. 31930 31966

Para el tratamiento de la pericarditis aguda o recurrente †

NOTA: Dosis expresada como base de naproxeno (200 mg de base de naproxeno equivalen a 220 mg de naproxeno sódico). 67419

para el tratamiento de la pericarditis aguda†

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

250 a 500 mg VO cada 12 horas, inicialmente; se puede aumentar la dosis hasta 1.500 mg/día si se tolera y es necesario y continuar durante 1 a 2
semanas, luego disminuir la dosis de 125 a 250 mg/día cada 1 a 2 semanas en combinación con colchicina. 67419

Niños y adolescentes de 2 a 17 años:

Dosis de 5 mg/kg por vía oral cada 12 horas durante 1 a 4 semanas; se han tolerado hasta 15 mg/kg/día. Considere reducir gradualmente la dosis
cada 1 a 2 semanas. 67418 67419

para el tratamiento de la pericarditis recurrente†

Dosis oral (comprimidos o suspensión de naproxeno)

Adultos:

250 to 500 mg PO every 12 hours, initially; may increase dose up to 1,500 mg/day if tolerated and needed and continue for at
least 2 to 4 weeks, then decrease dose by 125 to 250 mg/day every 1 to 2 weeks in combination with colchicine. 67419

Children and Adolescents 2 to 17 years:

5 mg/kg/dose PO every 12 hours for at least 2 to 4 weeks in combination with colchicine; up to 15 mg/kg/day has been tolerated.
Consider tapering dose gradually every 1 to 2 weeks. 67418 67419

For the treatment of uveitis†

Oral dosage (naproxen tablets or suspension)

Adults:
250 to 500 mg PO 2 times daily. 71021

Children and Adolescents:

5 to 7.5 mg/kg/dose (Max: 500 mg/dose) PO 2 times daily. 71024
Maximum Dosage Limits:

•Adults

Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day
PO.

•Geriatric

Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day
PO.

•Adolescents

Naproxen 1500 mg/day PO; Naproxen sodium up to 1650 mg/day PO for limited periods. For non-prescription use: 660 mg/day
PO.

•Children

>= 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; for non-prescription use, 660 mg/day PO.

2 to < 12 years: In clinical practice, 20 mg/kg/day PO not to exceed 1000 mg/day PO; non-prescription (self medication) use is not
recommended.

< 2 years: Safety and efficacy have not been established.

•Infants

Safety and efficacy have not been established.

•Neonates

Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Although specific guidelines are not available, dosage reduction may be necessary in patients with hepatic dysfunction.

Patients with Renal Impairment Dosing

CrCl >= 30 ml/min: No dosage adjustment needed.

CrCl < 30 ml/min: Not recommended.

Contraindications & Precautions

indicates a Black Box warning

Contraindications

coronary artery bypass graft surgery salicylate hypersensitivity

(CABG)

NSAID hypersensitivity

Precautions

acute bronchospasm cardiac arrhythmias dehydration

acute myocardial infarction cardiac disease ethanol ingestion

anemia cardiomyopathy geriatric

angina cerebrovascular disease GI bleeding

anticoagulant therapy coagulopathy GI perforation

asthma coronary artery disease heart failure

breast-feeding corticosteroid therapy hepatic disease

 hypertension nasal polyps reproductive risk

hypoalbuminemia obstetric delivery serious rash

hypovolemia peptic ulcer disease sodium restriction

infertility peripheral vascular disease stroke

labor pregnancy tachycardia

laboratory test interference renal disease thromboembolism

myocardial infarction renal failure tobacco smoking

myocardial infarction or stroke renal impairment urticaria

Naproxen is contraindicated in patients with known salicylate hypersensitivity or NSAID hypersensitivity (e.g., anaphylactic
reactions and serious skin reactions) and in patients with a history of asthma, urticaria, or other allergic-type reactions after
taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients.
A subpopulation of patients with asthma may have aspirin-sensitive asthma, which may include chronic rhinosinusitis
complicated by nasal polyps, severe and potentially fatal acute bronchospasm, and/or intolerance to aspirin and other NSAIDs.
Because cross-reactivity between aspirin and other NSAIDs has been reported, naproxen is contraindicated in patients with
aspirin-sensitive asthma. When naproxen is used in patients with preexisting asthma without known aspirin sensitivity, monitor
patients for changes in the signs and symptoms of asthma. Naproxen is contraindicated in patients with previous serious rash
or skin reactions to NSAIDs. The use of NSAIDs, including naproxen, may cause serious and potentially fatal skin reactions
including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Educate patients about the signs
and symptoms of serious skin reactions and to discontinue the use of naproxen at the first appearance of skin rash or
hypersensitivity. 32122

NSAIDs, including naproxen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration,
and GI perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse
events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Patients with a prior history
of peptic ulcer disease and/or GI bleeding who use NSAIDs have a more than 10-fold increased risk for developing a GI bleed
compared to patients without risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs
include longer duration of NSAID therapy, concomitant oral corticosteroids, anticoagulant therapy, aspirin, or selective
serotonin reuptake inhibitors (SSRIs), tobacco smoking, ethanol ingestion, older age, and poor general health status. Most
postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver
disease or coagulopathy are at increased risk for GI bleeding. To minimize GI risks in NSAID-treated patients, use the lowest
effective dosage for the shortest possible duration, and avoid administration of more than 1 NSAID at a time. In the setting of
concomitant low-dose aspirin use for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Avoid
NSAID use in higher risk populations unless the benefits are expected to outweigh the risks of bleeding; consider alternate
therapy other than NSAIDs in higher risk patients as well as those with active GI bleeding. Remain alert for signs and symptoms
of GI ulceration and bleeding during NSAID therapy. 32122

Naproxen is contraindicated in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of
thromboembolism, including myocardial infarction or stroke, was found through analysis of data regarding the use of a COX-2
selective nonsteroidal anti-inflammatory drug (NSAID) for the treatment of pain in the first 10 to 14 days after CABG surgery.
Naproxen, like all NSAIDs, may exacerbate heart failure and hypertension and may cause an increased risk of serious
cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Avoid the use of naproxen in patients
with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If naproxen is used in
patients with severe heart failure, monitor for signs of worsening heart failure. Trials demonstrated an approximately doubling
of hospitalizations for heart failure in patients treated with selective and nonselective NSAIDs compared to placebo-treated
patients. Additionally, fluid retention and edema have been observed with NSAID use. Consider the sodium content of naproxen
sodium in patients requiring severe sodium restriction. 32122 Caution is recommended when administering naproxen to patients
with cardiac disease, cardiomyopathy, cardiac arrhythmias (e.g., tachycardia), significant coronary artery disease (including acute
myocardial infarction, angina, or history of myocardial infarction), peripheral vascular disease, cerebrovascular disease (e.g.,
stroke, transient ischemic attack), hypertension, pre-existing renal disease, or fluid retention. 59937 Closely monitor blood
pressure during naproxen receipt. Use the lowest effective dose for the shortest duration possible to minimize the potential risk
for an adverse cardiovascular event. Inform patients to seek immediate medical attention if they experience any signs or
symptoms of a cardiovascular thrombotic event. Myocardial infarction or stroke can occur as early as the first weeks of using a
NSAID, and risk may increase with higher doses and longer duration of use. NSAIDs may increase the risk of a cardiovascular
thrombotic event in patients with or without underlying heart disease or risk factors for heart disease. Patients with known
heart disease or risk factors appear to have a greater likelihood of an event after NSAID use, likely due to a higher baseline risk.
32122 While comprehensive data regarding relative cardiovascular safety of any particular NSAID compared to other NSAIDs is
not available, celecoxib 100 mg twice daily was shown to be non-inferior to ibuprofen 600 to 800 mg 3 times daily or naproxen
375 to 500 mg twice daily for the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke in osteoarthritis
or rheumatoid arthritis adult patients with or at high risk for cardiovascular disease. Celecoxib had negligible effect on average
24-hour systolic blood pressure, while average 24-hour systolic pressures increased by 3.7 mmHg and 1.6 mmHg in patients
taking ibuprofen and naproxen, respectively. 56268 There is no consistent evidence that concomitant use of aspirin mitigates the
increased risk for cardiovascular thrombotic events. 32122 Guidelines state NSAIDs should not be administered to patients
presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction,
hypertension, heart failure, and myocardial rupture associated with their use. 55688 Observational data from a national registry
demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, cardiovascular-
related death, and all-cause mortality beginning the first week of treatment. An increased relative risk of death in NSAID users
continued during the follow-up period of 4 years. Data demonstrate that patients treated with NSAIDs were more likely to die in
the first year following a myocardial infarction compared to those not treated with NSAIDs. 32122

Correct volume status in dehydrated or hypovolemic patients before starting naproxen. Monitor renal function in patients with
renal impairment, heart failure, dehydration, or hypovolemia during naproxen use. Avoid naproxen use in patients with
advanced renal disease or renal failure unless the benefits are expected to outweigh the risk of worsening renal function. If
naproxen is used in patients with advanced renal disease, monitor patients for signs and symptoms of worsening renal function.
Naproxen is not recommended for use in patients with moderate to severe and severe renal impairment (CrCl less than 30
mL/minute). Renal toxicity has been observed in patients in whom renal prostaglandins have a compensatory role in the
maintenance of renal perfusion. In these patients, NSAID use may cause a dose-dependent reduction in prostaglandin
formation, and secondarily, renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this
reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking
diuretics and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and the elderly. Discontinuation of
NSAID therapy is usually followed by recovery to the pretreatment state. 32122

Use caution when high naproxen doses are required in patients with chronic alcoholic hepatic disease and other diseases with
decreased or abnormal plasma proteins (i.e., hypoalbuminemia). Dosage adjustment may be required; use the lowest effective
dose. In these patients, the total plasma concentration of naproxen may be reduced, but the plasma concentration of unbound
naproxen is increased. Additionally, patients with advanced liver disease are at increased risk for gastrointestinal bleeding. 32122

Monitor hemoglobin values periodically in patients with initial hemoglobin values of 10 g/dL or less who are to receive long-
term NSAID therapy. Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid
retention, or an incompletely described effect on erythropoiesis. 32122

Naproxen cannot be expected to substitute for corticosteroid therapy or treat corticosteroid insufficiency. Abrupt
discontinuation of corticosteroids may lead to disease exacerbation. Taper corticosteroid therapy slowly if a decision is made to
discontinue corticosteroids for patients on prolonged corticosteroid therapy; observe the patient closely for any adverse effects,
including adrenal insufficiency and exacerbation of symptoms of arthritis. Additionally, concomitant use of oral corticosteroid
therapy may increase the risk of GI bleeding in patients treated with NSAIDs. 32122

Geriatric adults are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal (GI), and renal adverse reactions.
Most spontaneous reports of fatal GI events are in the geriatric population. If the anticipated benefit outweighs these potential
risks, start naproxen therapy at the low end of the dosage range and monitor for adverse effects. Use caution when high doses
are required; some dosage adjustment may be necessary for older adults. Use the lowest effective dose. 32122 According to the
Beers Criteria, NSAIDs are considered potentially inappropriate medications (PIMs) in the older adult as NSAIDs may cause new
or worsening gastric and duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk
groups including those greater than 75 years of age, or those taking systemic corticosteroids, anticoagulants, or antiplatelet
medications. The risk of GI ulcers, gross bleeding, or perforation is cumulative with continued use. Avoid the chronic use of
NSAIDs in high-risk persons including those with a history of gastric or duodenal ulcers, unless other alternatives are not
effective, and the person can take a gastroprotective agent. The use of a gastroprotective agent, like a proton pump inhibitor or
misoprostol, reduces but does not eliminate GI risks. NSAIDs may also increase blood pressure and induce kidney injury. Avoid
use of NSAIDs in geriatric adults with the following conditions due to the potential for symptom exacerbation or adverse effects:
symptomatic heart failure (fluid retention, symptom exacerbation) or chronic kidney disease Stage 4 or higher (CrCl less than 30
mL/minute) (acute kidney injury, further decline of renal function). Use with caution in persons with asymptomatic heart
failure. 63923

Naproxen may cause laboratory test interference. Naproxen may decrease platelet aggregation and prolong bleeding time.
Consider this effect when bleeding times are determined. The administration of naproxen may also result in increased urinary
values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-di-nitrobenzene used
in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is
suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the
Porter-Silber test is to be used. Additionally, naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid
(5HIAA). Consider this effect when urinary 5-hydroxy indoleacetic acid is determined. 32122

Avoid naproxen use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature
closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. 32122 If NSAID treatment is deemed
necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider
ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if
oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in
pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These
adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently
reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment
discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In
some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis
were required. 66040 Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive.
There are no adequate and well-controlled studies of naproxen in pregnant women. 32122 Naproxen is not recommended in
labor and obstetric delivery because naproxen may adversely affect fetal circulation and inhibit uterine contractions, which may
increase the risk of uterine hemorrhage. 33886
Naproxen is excreted into breast milk in concentrations approximately equivalent to 1% of the maximal maternal plasma
concentrations. Consider the developmental and health benefits of breast-feeding along with the need for naproxen and any
potential adverse effects on the breastfed infant from naproxen or the underlying condition. 32122 44091 Naproxen use is usually
considered compatible with breast-feeding; other alternative analgesic and antiinflammatory drugs considered to be usually
compatible with breast-feeding include acetaminophen and ibuprofen. 27500

NSAIDs, such as naproxen, may pose a reproductive risk by delaying or preventing prostaglandin-mediated rupture of ovarian
follicles, which has been associated with reversible infertility. Small studies of women treated with NSAIDs demonstrated a
reversible delay in ovulation. Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing
infertility evaluation. 32122

Pregnancy
Avoid naproxen use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature
closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate. 32122 If NSAID treatment is deemed
necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider
ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if
oligohydramnios occurs and follow up according to clinical practice. Use of NSAIDs around 20 weeks gestation or later in
pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These
adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently
reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment
discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In
some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis
were required. 66040 Observational data regarding embryofetal risks of NSAID use during the first trimester is inconclusive.
There are no adequate and well-controlled studies of naproxen in pregnant women. 32122 Naproxen is not recommended in
labor and obstetric delivery because naproxen may adversely affect fetal circulation and inhibit uterine contractions, which may
increase the risk of uterine hemorrhage. 33886

Lactation
Naproxen is excreted into breast milk in concentrations approximately equivalent to 1% of the maximal maternal plasma
concentrations. Consider the developmental and health benefits of breast-feeding along with the need for naproxen and any
potential adverse effects on the breastfed infant from naproxen or the underlying condition. 32122 44091 Naproxen use is usually
considered compatible with breast-feeding; other alternative analgesic and antiinflammatory drugs considered to be usually
compatible with breast-feeding include acetaminophen and ibuprofen. 27500

Interactions
Interactions

Acebutolol Aliskiren; Hydrochlorothiazide, Amiloride; Hydrochlorothiazide,

HCTZ HCTZ
Acetaminophen; Aspirin
Alpha-blockers Aminolevulinic Acid
Acetaminophen; Aspirin, ASA;
Caffeine Alteplase Aminosalicylate sodium,
Aminosalicylic acid
Acetaminophen; Aspirin; Aluminum Hydroxide
Diphenhydramine Amlodipine
Aluminum Hydroxide; Magnesium
Acetaminophen; Ibuprofen Carbonate Amlodipine; Atorvastatin

Acyclovir Aluminum Hydroxide; Magnesium Amlodipine; Benazepril

Hydroxide
Adefovir Amlodipine; Celecoxib
Aluminum Hydroxide; Magnesium
Albuterol; Budesonide Hydroxide; Simethicone Amlodipine; Olmesartan

Aldesleukin, IL-2 Aluminum Hydroxide; Magnesium Amlodipine; Valsartan

Trisilicate
Alendronate Amlodipine; Valsartan;
Amikacin Hydrochlorothiazide, HCTZ
Alendronate; Cholecalciferol
Amiloride Amphotericin B
Aliskiren
Amphotericin B lipid complex (ABLC)
Amphotericin B liposomal (LAmB) Betrixaban Chlorthalidone

Anagrelide Bictegravir; Emtricitabine; Tenofovir Cholestyramine

Alafenamide
Angiotensin II receptor antagonists Choline Salicylate; Magnesium
Bismuth Subsalicylate Salicylate
Angiotensin-converting enzyme
inhibitors Bismuth Subsalicylate; Metronidazole; Cholinesterase inhibitors
Tetracycline
Antacids Ciclesonide
Bisoprolol
Antithrombin III Cidofovir
Bisoprolol; Hydrochlorothiazide,
Apixaban HCTZ Cilostazol

Aprepitant, Fosaprepitant Bivalirudin Cimetidine

Aprotinin Brimonidine; Timolol Ciprofloxacin

Argatroban Budesonide Citalopram

Aspirin, ASA Budesonide; Formoterol Citric Acid; Potassium Citrate;

Sodium Citrate
Aspirin, ASA; Butalbital; Caffeine Budesonide; Glycopyrrolate;
Formoterol Cladribine
Aspirin, ASA; Caffeine
Bumetanide Clevidipine
Aspirin, ASA; Caffeine; Orphenadrine
Bupivacaine; Meloxicam Clofarabine
Aspirin, ASA; Carisoprodol; Codeine
Busulfan Clopidogrel
Aspirin, ASA; Citric Acid; Sodium
Bicarbonate Butalbital; Aspirin; Caffeine; Codeine Colistimethate, Colistin, Polymyxin E

Aspirin, ASA; Dipyridamole Calcium Carbonate; Famotidine; Colistin

Magnesium Hydroxide
Aspirin, ASA; Omeprazole Corticosteroids
Calcium Chloride
Aspirin, ASA; Oxycodone Cortisone
Calcium Phosphate, Supersaturated
Atazanavir Cyclosporine
Calcium-channel blockers
Atazanavir; Cobicistat Cytarabine, ARA-C
Candesartan
Atenolol Dabigatran
Candesartan; Hydrochlorothiazide,
Atenolol; Chlorthalidone HCTZ Dabrafenib

Auranofin Cannabidiol Dacarbazine, DTIC

Azathioprine Capreomycin Dalteparin

Azelastine; Fluticasone Captopril Darunavir; Cobicistat; Emtricitabine;

Tenofovir alafenamide
Azilsartan
Captopril; Hydrochlorothiazide,
Dasatinib
Azilsartan; Chlorthalidone HCTZ

Carmustine, BCNU Deferasirox

Bacitracin
Carteolol Deflazacort
Beclomethasone
Carvedilol Delafloxacin
Benazepril
Desmopressin
Benazepril; Hydrochlorothiazide, Cefotaxime
HCTZ Desvenlafaxine
Celecoxib
Benzoic Acid; Hyoscyamine; Celecoxib; Tramadol Dexamethasone
Methenamine; Methylene Blue;
Phenyl Salicylate Chlorambucil Diclofenac

Beta-blockers Chlorothiazide Diclofenac; Misoprostol

Betamethasone Diflunisal
Chlorpheniramine; Ibuprofen;
Pseudoephedrine Digoxin
Betaxolol
Diltiazem Eprosartan Gemfibrozil

Diphenhydramine; Ibuprofen Eprosartan; Hydrochlorothiazide, Gemifloxacin

HCTZ
Dipyridamole Gentamicin
Eptifibatide
Docetaxel Ginger, Zingiber officinale
Erlotinib
Donepezil Ginkgo, Ginkgo biloba
Escitalopram
Donepezil; Memantine Glimepiride
Esmolol
Doravirine; Lamivudine; Tenofovir Glipizide
disoproxil fumarate Ethacrynic Acid
Glipizide; Metformin
Dorzolamide; Timolol Ethanol
Glyburide
Doxazosin Ethiodized Oil
Glyburide; Metformin
Drospirenone Ethotoin
Gold
Drospirenone; Estetrol Etidronate
Guanfacine
Drospirenone; Estradiol Etodolac
H2-blockers
Drospirenone; Ethinyl Estradiol Famotidine
Heparin
Drospirenone; Ethinyl Estradiol; Felodipine
Levomefolate Hyaluronidase, Recombinant;
Fenofibric Acid Immune Globulin
Duloxetine
Fenoprofen Hydantoins
Edoxaban
Floxuridine Hydrochlorothiazide, HCTZ
Efavirenz; Emtricitabine; Tenofovir
Disoproxil Fumarate Fludrocortisone Hydrochlorothiazide, HCTZ;
Moexipril
Efavirenz; Lamivudine; Tenofovir Flunisolide
Disoproxil Fumarate Hydrocodone; Ibuprofen
Fluorouracil, 5-FU
Elexacaftor; tezacaftor; ivacaftor Hydrocortisone
Fluoxetine
Eltrombopag Hyoscyamine; Methenamine;
Flurbiprofen Methylene Blue; Phenyl Salicylate;
Elvitegravir; Cobicistat; Emtricitabine; Sodium Biphosphate
Fluticasone
Tenofovir Alafenamide
Ibandronate
Elvitegravir; Cobicistat; Emtricitabine; Fluticasone; Salmeterol
Tenofovir Disoproxil Fumarate Ibritumomab Tiuxetan
Fluticasone; Umeclidinium; Vilanterol
Emtricitabine Ibuprofen
Fluticasone; Vilanterol
Emtricitabine; Rilpivirine; Tenofovir Ibuprofen lysine
Fluvoxamine
alafenamide
Ibuprofen; Famotidine
Fondaparinux
Emtricitabine; Rilpivirine; Tenofovir
Disoproxil Fumarate Ibuprofen; Oxycodone
Formoterol; Mometasone
Emtricitabine; Tenofovir alafenamide Ibuprofen; Pseudoephedrine
Foscarnet
Emtricitabine; Tenofovir Disoproxil Iloprost
Fosinopril
Fumarate Immune Globulin IV, IVIG, IGIV
Fosinopril; Hydrochlorothiazide,
Enalapril, Enalaprilat HCTZ Indapamide
Enalapril; Hydrochlorothiazide, Fosphenytoin Indomethacin
HCTZ
Furosemide Inotersen
Enoxaparin
Galantamine Iodine; Potassium Iodide, KI
Entecavir
Ganciclovir Iodixanol
Eplerenone
Garlic, Allium sativum Iohexol
Epoprostenol
Iomeprol Mechlorethamine, Nitrogen Mustard Olmesartan; Hydrochlorothiazide,
HCTZ
Ionic Contrast Media Meclofenamate Sodium
Olopatadine; Mometasone
Iopamidol Mefenamic Acid
Omacetaxine
Iopromide Meloxicam
Omeprazole; Sodium Bicarbonate
Ioversol Mesalamine, 5-ASA
Oritavancin
Irbesartan Methenamine; Sodium Salicylate
Oxaprozin
Irbesartan; Hydrochlorothiazide, Methotrexate
HCTZ Paclitaxel
Methoxsalen
Isosulfan Blue Pamidronate
Methyldopa
Isradipine Paroxetine
Methylprednisolone
Ivacaftor Pentamidine
Methylsulfonylmethane, MSM
Ketoprofen Pentosan
Metolazone
Ketorolac Pentostatin
Metoprolol
Labetalol Perindopril
Metoprolol; Hydrochlorothiazide,
Lamivudine; Tenofovir Disoproxil HCTZ Perindopril; Amlodipine
Fumarate
Mifepristone Phenoxybenzamine
Leflunomide
Milnacipran Phentolamine
Levamlodipine
Mitoxantrone Phenytoin
Levobunolol
Moexipril Photosensitizing agents (topical)
Levofloxacin
Mometasone Physostigmine
Levomefolate
Moxifloxacin Pindolol
Levomilnacipran
Nabumetone Pioglitazone; Glimepiride
Lisinopril
Nadolol Piroxicam
Lisinopril; Hydrochlorothiazide,
HCTZ Nebivolol Platelet Inhibitors

Lithium Nelarabine Pneumococcal Vaccine, Polyvalent

Lomustine, CCNU Neomycin Polyethylene Glycol; Electrolytes

Losartan Neostigmine Polyethylene Glycol; Electrolytes;

Ascorbic Acid
Losartan; Hydrochlorothiazide, HCTZ Neostigmine; Glycopyrrolate
Polymyxin B
Lumacaftor; Ivacaftor Nicardipine
Potassium
Lumacaftor; Ivacaftor NIFEdipine
Potassium Acetate
Macimorelin Nimodipine
Potassium Bicarbonate
Mafenide Nisoldipine
Potassium Chloride
Magnesium Hydroxide Nizatidine
Potassium Citrate
Magnesium Salicylate Non-Ionic Contrast Media
Potassium Citrate; Citric Acid
Magnesium Salts Ofloxacin
Potassium Gluconate
Magnesium Sulfate; Potassium Olanzapine; Fluoxetine
Sulfate; Sodium Sulfate Potassium Iodide, KI
Olmesartan
Mannitol Pralatrexate
Olmesartan; Amlodipine;
Mecamylamine Hydrochlorothiazide, HCTZ Prasugrel
 Prazosin Spironolactone tobacco

Prednisolone Spironolactone; Hydrochlorothiazide, Tobramycin

HCTZ
Prednisone Tolmetin
Streptomycin
Probenecid Torsemide
Sucralfate
Probenecid; Colchicine Trandolapril
Sulfadiazine
Procarbazine Trandolapril; Verapamil
Sulfamethoxazole; Trimethoprim,
Propranolol SMX-TMP, Cotrimoxazole Trazodone

Pyridostigmine Sulfasalazine Treprostinil

Quinapril Sulfonamides Triamcinolone

Quinapril; Hydrochlorothiazide, Sulfonylureas Triamterene

HCTZ
Sulindac Triamterene; Hydrochlorothiazide,
Quinolones HCTZ
Tacrolimus
Ramipril Urea
Telavancin
Ranitidine Valacyclovir
Telmisartan
Reteplase, r-PA Valganciclovir
Telmisartan; Amlodipine
Risedronate Valsartan
Telmisartan; Hydrochlorothiazide,
Rivaroxaban HCTZ Valsartan; Hydrochlorothiazide,
HCTZ
Rivastigmine Temozolomide
Vancomycin
Sacubitril; Valsartan Tenecteplase
Vemurafenib
Salsalate Tenofovir Alafenamide
Venlafaxine
Selective serotonin reuptake Tenofovir Alafenamide
inhibitors Verapamil
Tenofovir Disoproxil Fumarate
Sertraline Verteporfin
Terazosin
Sodium Bicarbonate Vigabatrin
Teriflunomide
Sodium Phosphate Monobasic Vilazodone
Monohydrate; Sodium Phosphate Tezacaftor; Ivacaftor
Dibasic Anhydrous Voclosporin
Thiazide diuretics
Sodium picosulfate; Magnesium Vorapaxar
oxide; Anhydrous citric acid Thioguanine, 6-TG
Voriconazole
Sodium Sulfate; Magnesium Sulfate; Thrombolytic Agents
Vortioxetine
Potassium Chloride
Ticagrelor
Warfarin
Sotalol
Timolol
Sparsentan Zoledronic Acid
Tirofiban

Acebutolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Acetaminophen; Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171

Acetaminophen; Aspirin: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due
to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after
discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171

Acetaminophen; Aspirin; diphenhydrAMINE: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171

Acetaminophen; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Acyclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of acyclovir and
nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. 34408 56268

Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as nonsteroidal antiinflammatory drugs
may increase the risk of developing nephrotoxicity even in patients who have normal renal function. The use of adefovir with
NSAIDs may be done cautiously. As stated in the current adefovir prescribing information, 'Ibuprofen (800 mg PO three times
daily), when given concomitantly with adefovir dipivoxil, increased the adefovir Cmax by 33% and AUC by 23%, as well as
urinary recovery. The increase appears to be due to higher oral bioavailability, not a reduction in renal clearance of adefovir.' In
an in vitro investigation, the antiviral effect of adefovir was unaltered and the renal proximal tubule accumulation of adefovir
was inhibited by the presence of a NSAID. Adefovir is efficiently transported by the human renal organic anion transporter 1,
and the presence of this transporter appears to mediate the accumulation of the drug in renal proximal tubules. The in vitro
study suggests that the use of a NSAID with adefovir may potentially reduce the nephrotoxic potential of adefovir. Of course,
NSAIDs are associated with nephrotoxicity of their own; therefore, further data on the interaction between NSAIDs and adefovir
in humans are needed. 27615

Albuterol; Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893
Aldesleukin, IL-2: (Major) Aldesleukin, IL-2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic
effects, such as nonsteroidal antiinflammatory agents (NSAIDs), with Aldesleukin, IL-2 may increase the risk of kidney
dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL-2 treatment may delay elimination of
concomitant medications and increase the risk of adverse events from those drugs. 41853

Alendronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and nonsteroidal
antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest
concomitant use introduces little additional risk for adverse effects for most patients. 28644 52249

Alendronate; Cholecalciferol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of alendronate and
nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data
suggest concomitant use introduces little additional risk for adverse effects for most patients. 28644 52249

Aliskiren: (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of vasodilatory
prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal
function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further deterioration of renal
function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and renal function should
be monitored closely when an NSAID is administered to a patient taking aliskiren. 30489 33200

Aliskiren; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and
loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID)
and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) NSAIDs may attenuate the antihypertensive effects of aliskiren by inhibiting the synthesis of
vasodilatory prostaglandins. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with
compromised renal function who are being treated with NSAIDs, the coadministration of aliskiren may result in a further
deterioration of renal function, including acute renal failure. These effects are usually reversible. Therefore, blood pressure and
renal function should be monitored closely when an NSAID is administered to a patient taking aliskiren. 30489 33200
Alpha-blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Alteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic
effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs
concurrently should be monitored closely for bleeding. 28469 30569

Aluminum Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use
should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
6112 8934

Aluminum Hydroxide; Magnesium Carbonate: (Minor) Concomitant administration of antacids can delay the absorption of
naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are
separated by at least 2 hours. 6112 8934

Aluminum Hydroxide; Magnesium Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of
naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are
separated by at least 2 hours. 6112 8934

Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Minor) Concomitant administration of antacids can delay the absorption
of naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration
are separated by at least 2 hours. 6112 8934

Aluminum Hydroxide; Magnesium Trisilicate: (Minor) Concomitant administration of antacids can delay the absorption of
naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are
separated by at least 2 hours. 6112 8934

Amikacin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory
drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin. 28370 30110 30268

aMILoride: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some
patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood
flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight
gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a
diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic
efficacy. 30489 48492
aMILoride; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and
loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID)
and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in
some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal
blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and
weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID
and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and
diuretic efficacy. 30489 48492

Aminolevulinic Acid: (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory drugs
(NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs before and
during photodynamic therapy may be advisable. 42968

Aminosalicylate sodium, Aminosalicylic acid: (Major) Avoid concomitant use of naproxen with aminosalicylic acid due to an
increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171

amLODIPine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

amLODIPine; Atorvastatin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

amLODIPine; Benazepril: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal
anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons
who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may
result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 32122 61325

amLODIPine; Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 28317 32122 (Moderate) If nonsteroidal
anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs
and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment
in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure.
This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs
cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to
renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients
who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage.
Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive
agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery
disease. 24233 26486 27388 30489

amLODIPine; Olmesartan: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly,
volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in
deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 27388 27991 28608 29130
32122 60860

amLODIPine; Valsartan: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly,
volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in
deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 27388 27991 28608 29130
32122 60860

amLODIPine; Valsartan; hydroCHLOROthiazide, HCTZ: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an
antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and
blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent
NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in
patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction
in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in
blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to
maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk
of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related
decreases in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate)
Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-
inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In
persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and
NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of
diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and
thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492

Amphotericin B lipid complex (ABLC): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including
nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal
function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
28333 30268

Amphotericin B liposomal (LAmB): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including
nonsteroidal antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal
function carefully during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
28333 30268

Amphotericin B: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including nonsteroidal
antiinflammatory drugs (NSAIDs), may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully
during concurrent therapy. Amphotericin B dosage reduction may be necessary if renal impairment occurs. 28333 30268

Anagrelide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Angiotensin II receptor antagonists: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860

Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325

Antacids: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use should not
be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours. 6112 8934

Antithrombin III: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with
other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Apixaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents
known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory
response closely during concurrent use. 52739

Aprepitant, Fosaprepitant: (Minor) Use caution if naproxen and aprepitant are used concurrently and monitor for a possible
decrease in the efficacy of naproxen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same
drug interactions. Naproxen is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate,
tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide
AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4,
15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and
15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80
mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-
warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of
aprepitant. 30676 34493 34495 40027

Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can
affect renal function, such as NSAIDs, as the risk of renal impairment may be increased. 5204

Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946
Aspirin, ASA: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to the
increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after
discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171

Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171
Aspirin, ASA; Caffeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due to
the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after
discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171

Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171

Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171

Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171 (Minor) Concomitant administration of antacids can delay the absorption of
naproxen. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are
separated by at least 2 hours. 6112 8934

Aspirin, ASA; Dipyridamole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended
due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events
after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171 (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and
chronic nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Aspirin, ASA; Omeprazole: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due
to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after
discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171

Aspirin, ASA; oxyCODONE: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not recommended due
to the increased risk of bleeding and renal impairment. Because there may be an increased risk of cardiovascular events after
discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the washout period, for
patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of an NSAID that does
not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A pharmacodynamic study
demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose
immediate-release aspirin, with the interaction most marked during the washout period of naproxen. There is reason to expect
that the interaction would be present with prescription doses of naproxen or with enteric-coated low-dose aspirin; however, the
peak interference with aspirin function may be later than observed in the study due to the longer washout period. A decrease in
antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with low-dose immediate-release aspirin 81
mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after discontinuation of naproxen on day 11 while
aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before
aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The
interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose
immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation
(84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies showed that the concomitant use
of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a
clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI
adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose aspirin for cardiovascular
protection. 32122 61171

Atazanavir: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for elevated
naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this enzyme.
11351 28142

Atazanavir; Cobicistat: (Minor) Caution is warranted when atazanavir is administered with naproxen as there is a potential for
elevated naproxen concentrations. In vitro data suggest naproxen is a substrate for CYP2C8; atazanavir is a weak inhibitor of this
enzyme. 11351 28142
Atenolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic
efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide
diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory
drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Auranofin: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents,
such as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy. 30110
30268

azaTHIOprine: (Moderate) NSAIDs should be used with caution in patients receiving immunosuppressives as they may mask
fever, pain, swelling and other signs and symptoms of an infection. 6144

Azelastine; Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Azilsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Azilsartan; Chlorthalidone: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II
blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be
diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of
angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these
effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492

Bacitracin: (Major) Avoid concurrent use of bacitracin with nonsteroidal antiinflammatory drugs. Coadministration may increase
the risk for drug-induced nephrotoxicity. 31047 56268

Beclomethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Benazepril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Benazepril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Avoid concomitant use of naproxen with phenyl
salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122
61171

Beta-blockers: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Betamethasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Betaxolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and
nonsteroidal antiinflammatory drugs (NSAIDs) are used concomitantly. Coadministration of betrixaban and NSAIDs may
increase the risk of bleeding. 62037

Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is
administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is
primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of
tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase
concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269 60688
(Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during
concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce
renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse
reactions. 35893 51664 64014

Bismuth Subsalicylate: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to an increased risk of
gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171

Bismuth Subsalicylate; metroNIDAZOLE; Tetracycline: (Major) Avoid concomitant use of naproxen with bismuth subsalicylate due to
an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171

Bisoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Bisoprolol; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and
loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID)
and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory
drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Bivalirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Brimonidine; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory
drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Budesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Budesonide; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Bumetanide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor
the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs
concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some
patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood
flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight
gain. 30489 48492

BUPivacaine; Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to
the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 29611
32122

Busulfan: (Major) Due to the thrombocytopenic effects of busulfan, an additive risk of bleeding may be seen in patients receiving
concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 4736 5170
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of analgesic doses of aspirin and naproxen is generally not
recommended due to the increased risk of bleeding and renal impairment. Because there may be an increased risk of
cardiovascular events after discontinuation of naproxen due to the interference with the antiplatelet effect of aspirin during the
washout period, for patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider use of
an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics as appropriate. A
pharmacodynamic study demonstrated that lower dose naproxen (220mg/day or 220mg twice daily) interfered with the
antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of
naproxen. There is reason to expect that the interaction would be present with prescription doses of naproxen or with enteric-
coated low-dose aspirin; however, the peak interference with aspirin function may be later than observed in the study due to the
longer washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with
low-dose immediate-release aspirin 81 mg/day (93.1%) vs. aspirin alone (98.7%). The interaction was observed even after
discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater
when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes
before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was
given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11
after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). Controlled clinical studies
showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than
the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly
increased incidence of GI adverse reactions as compared to use of the NSAID alone. Naproxen is not a substitute for low dose
aspirin for cardiovascular protection. 32122 61171

Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Avoid concomitant use of enteric-coated, delayed-release
naproxen and H2-blockers due to the gastric pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen
tablets are designed to dissolve at a pH of 6 or more. 32122

Calcium Chloride: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use
should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
6112 8934

Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function
such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy in patients taking
sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. 32159 32160

Calcium-channel blockers: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Candesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Candesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during
concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of
angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal
function, coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including
possible acute renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood
pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during
concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent
reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the
risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid
retention which may blunt the cardiovascular effects of diuretics. 35893 48492

Cannabidiol: (Moderate) Consider a dose reduction of naproxen as clinically appropriate, if adverse reactions occur when
administered with cannabidiol. Increased naproxen exposure is possible. Naproxen is a CYP2C9 substrate. In vitro data predicts
inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions. 34493 34495 63309
Capreomycin: (Major) Because capreomycin is primarily eliminated by the kidney, coadministration with other potentially
nephrotoxic drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may increase serum concentrations of either drug.
Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients
who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. 44155

Captopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Captopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492

Carmustine, BCNU: (Major) Due to the thrombocytopenic effects of carmustine, an additive risk of bleeding may be seen in
patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. These additive effects may not occur for at least 6 weeks after the administration of carmustine due to the
delayed myelosuppressive effects of carmustine. 5170 5946

Carteolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Carvedilol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic
agents, such as aminoglycosides, nonsteroidal antiinflammatory drugs (NSAIDs), and loop diuretics. Carefully monitor renal
function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the
combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as
singular agents. Limited but conflicting data with other cephalosporins have been noted. 28646 29912 57694 57695 58208

Celecoxib: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID toxicities
including but not limited to GI bleeding, GI perforation, or peptic ulcers. 28317 32122

Celecoxib; Tramadol: (Major) Avoid concomitant use of celecoxib with any other NSAID due to the risk of additive serious NSAID
toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 28317 32122

Chlorambucil: (Major) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. 4757 5170

Chlorothiazide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use.
NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide
diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. 35893 48492

Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Chlorthalidone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use.
NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide
diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. 35893 48492

Cholestyramine: (Minor) The absorption of NSAIDs can be delayed if cholestyramine is concomitantly administered. 8934

Choline Salicylate; Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with choline salicylate due to an increased risk
of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171 (Major) Avoid concomitant use
of naproxen with magnesium salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or
no increase in efficacy. 32122 61171

Cholinesterase inhibitors: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors,
leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of
active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow
inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data
at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Ciclesonide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory
drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893
Cidofovir: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is
contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning
cidofovir. 28388

Cilostazol: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Cimetidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH
elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
32122

Ciprofloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Citalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127

Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium
supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of
hyperkalemia. 30272 53793

Cladribine: (Major) Due to the thrombocytopenic effects of cladribine, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5170 7226

Clevidipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Clofarabine: (Major) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients
receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an
additional risk factor for bleeding. 5170 7557

Clopidogrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Colistimethate, Colistin, Polymyxin E: (Major) The administration of colistimethate sodium may increase the risk of developing
nephrotoxicity, even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase
the risk for nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are
coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic
drugs, including nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug.
33636

Colistin: (Major) The administration of colistimethate sodium may increase the risk of developing nephrotoxicity, even in
patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for
nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since
colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including
nonsteroidal antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug. 33636

Corticosteroids: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Cortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory
drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

cycloSPORINE: (Moderate) Serum creatinine ,potassium concentrations, and cyclosporine concentrations should be closely
monitored when systemic cyclosporine is given with nonsteroidal antiinflammatory drugs (NSAIDs). Renal dysfunction
associated with cyclosporine may be potentiated by concurrent usage of NSAIDs. The effects of NSAIDs on the production of
renal prostaglandins may cause changes in the elimination of cyclosporine. Potentiation of renal dysfunction may especially
occur in a dehydrated patient. Patients should be monitored for signs and symptoms of cyclosporine toxicity and infection, as
NSAIDs may mask fever, pain, or swelling. Increased tear production was not seen in patients receiving ophthalmic NSAIDs or
using punctual plugs concurrently with cyclosporine ophthalmic emulsion. 29198
Cytarabine, ARA-C: (Major) The main toxic effect of cytarabine, ARA-C is bone marrow suppression with leukopenia,
thrombocytopenia and anemia. Due to the thrombocytopenic effects of cytarabine, an additive risk of bleeding may be seen in
patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an
additional risk factor for bleeding. Dipyridamole can block membrane transport of cytarabine in tumor cells, therefore
decreasing its antineoplastic activity. 5170 7945

Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare
provider immediately if coadministration of dabigatran and a nonsteroidal antiinflammatory drug (NSAID) is necessary.
Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic NSAID
therapy. 42121
Dabrafenib: (Moderate) Use dabrafenib and naproxen together with caution; naproxen exposure may be decreased. Use an
alternate agent in place of naproxen if possible. If concomitant use with cannot be avoided, monitor patients for loss of
naproxen efficacy. Dabrafenib is a weak CYP29 inducer and naproxen is a CYP2C9 substrate. When a single-dose of a sensitive
CYP2C9 substrate was administered after 15 days of dabrafenib 150 mg twice daily, the AUC value of the CYP2C9 substrate was
decreased by 37%. 11351 11353 54802

Dacarbazine, DTIC: (Major) Leukopenia and thrombocytopenia are common toxicities of dacarbazine, DTIC. Due to the
thrombocytopenic effects of dacarbazine, an additive risk of bleeding may be seen in patients receiving concomitant
anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition,
large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. 5170 7996

Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir
alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs).
Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion.
Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may
increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269
60688 (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during
concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce
renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse
reactions. 35893 51664 64014

Dasatinib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding
may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89
chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an
additional risk factor for bleeding. Caution should be exercised if patients are required to take medications that inhibit platelet
function or anticoagulants concomitantly with dasatinib. 32387 5170

Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution
when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including NSAIDs. In
addition, coadministration of deferasirox with other potentially nephrotoxic drugs, including NSAIDs, may increase the acute
renal failure. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic
drugs concomitantly. 31807

Deflazacort: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory
drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Delafloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated
with hyponatremia including NSAIDs. Use combination with caution, and monitor patients for signs and symptoms of
hyponatremia. A woman who took both desmopressin and ibuprofen was found in a comatose state. As her serum sodium
concentration was 121 mmol/L, and her plasma osmolality was low in the presence of a high-normal urine osmolality and
normal sodium excretion, she was treated with fluid restriction. Her serum sodium concentration was 124 mmol/L within a day
and was 135 mmol/L by the second day. The woman had previously received desmopressin without the development of clinical
symptoms of hyponatremia. 10457 10458 29202

Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by desvenlafaxine due to platelet serotonin depletion, possibly
increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae,
hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be monitored for signs and
symptoms of bleeding while taking desvenlafaxine with NSAIDs. 28275 29934

dexAMETHasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Diclofenac: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30115 32122
Diclofenac; miSOPROStol: (Major) Avoid concomitant use of diclofenac with any other NSAID, including COX-2 inhibitors, due to
the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30115
32122

Diflunisal: (Major) Avoid concomitant use of diflunisal with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. Additionally,
concomitant administration of naproxen and diflunisal significantly decreased the urinary excretion of naproxen and its
glucuronide metabolite; naproxen and diflunisal plasma concentrations were unaffected. 32122 49143

Digoxin: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased
serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular
filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible
digoxin toxicity and reduce digoxin dose as necessary. 28272

dilTIAZem: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

diphenhydrAMINE; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive
serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Dipyridamole: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

DOCEtaxel: (Major) Due to the thrombocytopenic effects of docetaxel, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors (including aspirin), strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5170 5235

Donepezil: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Donepezil; Memantine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors,
leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of
active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow
inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data
at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Doravirine; lamiVUDine; Tenofovir disoproxil fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or
recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute
renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple
NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal
dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus,
urine glucose, and urine protein prior to, and periodically during, treatment. 28193 30268

Dorzolamide; Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory
drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Doxazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489
Drospirenone: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Other drugs
that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and monitoring
of serum potassium in the 1st month of concurrent therapy is recommended. 4716
Drospirenone; Estetrol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium.
Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and
monitoring of serum potassium in the 1st month of concurrent therapy is recommended. 4716

Drospirenone; Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium.
Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with NSAIDs, and
monitoring of serum potassium in the 1st month of concurrent therapy is recommended. 4716

Drospirenone; Ethinyl Estradiol: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase serum
potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment with
NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. 4716
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Drospirenone has antimineralocorticoid effects; the progestin may increase
serum potassium. Other drugs that may have additive effects on serum potassium with drospirenone include chronic treatment
with NSAIDs, and monitoring of serum potassium in the 1st month of concurrent therapy is recommended. 4716 (Minor) L-
methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations of L-methylfolate may
be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased efficacy of L-methylfolate if
these agents are used together. 35581

DULoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant duloxetine and nonsteroidal
antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in
hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with
serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 29934

Edoxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other agents
known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and laboratory
response closely during concurrent use. 29732 40621 49946

Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or
recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute
renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple
NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal
dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus,
urine glucose, and urine protein prior to, and periodically during, treatment. 28193 30268 (Moderate) Monitor for nonsteroidal
antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase
NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular
secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. 35893 51664 64014

Efavirenz; lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or
recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute
renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple
NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal
dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus,
urine glucose, and urine protein prior to, and periodically during, treatment. 28193 30268

Elexacaftor; tezacaftor; ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with
CYP2C9 substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration
may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. 34493
48524

Eltrombopag: (Moderate) Eltrombopag is a UDP-glucuronyltransferase inhibitor. NSAIDs are a substrate of UDP-

glucuronyltransferases. The significance or effect of this interaction is not known; however, elevated concentrations of the
NSAID are possible. Monitor patients for adverse reactions if eltrombopag is administered with an NSAID. 40392

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir
alafenamide is administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs).
Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion.
Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may
increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269
60688 (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during
concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce
renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse
reactions. 35893 51664 64014 (Moderate) The plasma concentrations of naproxen may be decreased when administered
concurrently with elvitegravir. Patients may experience decreased analgesic or anti-inflammatory effects when these drugs are
coadministered. Elvitegravir is a CYP2C9 inducer, while naproxen is a CYP2C9 substrate. 34493 34495 51664 58001

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently
with or recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases
of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or
multiple NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk
for renal dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum
phosphorus, urine glucose, and urine protein prior to, and periodically during, treatment. 28193 30268 (Moderate) Monitor for
nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use
may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for
active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. 35893 51664 64014
(Moderate) The plasma concentrations of naproxen may be decreased when administered concurrently with elvitegravir. Patients
may experience decreased analgesic or anti-inflammatory effects when these drugs are coadministered. Elvitegravir is a CYP2C9
inducer, while naproxen is a CYP2C9 substrate. 34493 34495 51664 58001

Emtricitabine: (Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events
during concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that
reduce renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of
adverse reactions. 35893 51664 64014

Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is
administered in combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is
primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of
tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase
concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269 60688
(Moderate) Monitor for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during
concomitant use. Concomitant use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce
renal function or compete for active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse
reactions. 35893 51664 64014

Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or
recently after a nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute
renal failure, some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple
NSAIDs were initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal
dysfunction. If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus,
urine glucose, and urine protein prior to, and periodically during, treatment. 28193 30268 (Moderate) Monitor for nonsteroidal
antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase
NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular
secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. 35893 51664 64014
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in
combination with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted
via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir
alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of
tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269 60688 (Moderate) Monitor
for nonsteroidal antiinflammatory drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant
use may increase NSAID or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for
active tubular secretion, such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. 35893 51664 64014

Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a
nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure,
some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were
initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction.
If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose,
and urine protein prior to, and periodically during, treatment. 28193 30268 (Moderate) Monitor for nonsteroidal antiinflammatory
drug (NSAID) or emtricitabine-related adverse events during concomitant use. Concomitant use may increase NSAID or
emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion,
such as NSAIDs and emtricitabine, may increase the risk of adverse reactions. 35893 51664 64014

Enalapril, Enalaprilat: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-
converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE
inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Enalapril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492
Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal
antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and
laboratory monitoring. 29732

Entecavir: (Moderate) The manufacturer of entecavir recommends monitoring for adverse effects when coadministered with
NSAIDs. Entecavir is primarily eliminated by the kidneys; NSAIDs can affect renal function. Concurrent administration may
increase the serum concentrations of entecavir and adverse events. 31230
Eplerenone: (Major) Monitor serum potassium and serum creatinine concentrations within 3 to 7 days of initiating
coadministration of eplerenone and nonsteroidal antiinflammatory drugs (NSAIDs), and monitor blood pressure. The
concomitant use of other potassium-sparing antihypertensives with NSAIDs has been shown to reduce the antihypertensive
effect in some patients and result in severe hyperkalemia in patients with impaired renal function. Patients who develop
hyperkalemia may continue eplerenone with proper dose adjustment; eplerenone dose reduction decreases potassium
concentrations. 27990

Epoprostenol: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including
renal and peripheral vasoactive pathways. 4087

Eprosartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Eprosartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Eptifibatide: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and
vomiting) if coadministration of erlotinib with nonsteroidal antiinflammatory drugs (NSAIDs) is necessary. Permanently
discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib
ranged from 0.1% to 0.4%, including fatal cases. Patients receiving concomitant NSAIDs may be at increased risk of perforation.
30555

Escitalopram: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127

Esmolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Ethacrynic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully
monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and
NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics
in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal
blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and
weight gain. 30489 48492

Ethanol: (Major) Advise patients to avoid alcohol and alcohol-containing products while taking NSAIDs. Concomitant ingestion
of alcohol with NSAIDs increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol is a mucosal irritant
and NSAIDs decrease platelet aggregation. Routine ingestion of alcohol and NSAIDs can cause significant GI bleeding, which
may or may not be overt. Even occasional concomitant use of NSAIDs and alcohol should be avoided. Chronic alcohol ingestion
is often associated with hypoprothrombinemia and this condition increases the risk of bleeding. 30115 30427 30569 31949

Ethiodized Oil: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Ethotoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. 6112

Etidronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and nonsteroidal
antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest
concomitant use introduces little additional risk for adverse effects for most patients. 28655

Etodolac: (Major) Avoid concomitant use of etodolac with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 45875

Famotidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH
elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
32122
Felodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant
use of fenofibric acid with CYP2C9 substrates, such as naproxen, has not been formally studied. Fenofibric acid may theoretically
increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range.
Monitor the therapeutic effect of naproxen during coadministration with fenofibric acid. 11351 11353 49952

Fenoprofen: (Major) Avoid concomitant use of fenoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30524 32122

Floxuridine: (Major) Due to the thrombocytopenic effects of floxuridine, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5170 7446

Fludrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Flunisolide: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory
drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Fluorouracil, 5-FU: (Major) Due to the thrombocytopenic effects of fluorouracil, 5-FU, an additive risk of bleeding may be seen in
patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. 5170 5763

FLUoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127

Flurbiprofen: (Major) Avoid concomitant use of flurbiprofen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30241 32122

Fluticasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory
drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Fluticasone; Salmeterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Fluticasone; Vilanterol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

fluvoxaMINE: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127

Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with
other agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Formoterol; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Foscarnet: (Minor) The risk of renal toxicity may be increased if foscarnet is used in conjuction with other nephrotoxic agents,
such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor renal function carefully during concurrent therapy. 28377 30268

Fosinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325
Fosinopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492

Fosphenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. 6112

Furosemide: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs
(NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop
diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. 32122 48492

Galantamine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Ganciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with ganciclovir should be done cautiously to avoid
additive nephrotoxicity. Monitor renal function carefully if concomitant therapy is required. 32676

Garlic, Allium sativum: (Minor) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are
available, garlic should be used cautiously in patients receiving drugs with a known potential risk for bleeding such as
nonsteroidal antiinflammatory drugs (NSAIDs). 25588 63043

Gemfibrozil: (Moderate) Use naproxen and gemfibrozil together with caution. Naproxen is a substrate of CYP2C8, and gemfibrozil
is a strong CYP2C8 inhibitor. Coadministration may result in a significant increase in naproxen exposure. A dose reduction of
naproxen may be required if used concomitantly with gemfibrozil. 34493 34495 48366 56579 57620

Gemifloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Gentamicin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-
inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as gentamicin. 28370 30110 30268

Ginger, Zingiber officinale: (Minor) Patients receiving regular therapy with nonsteroidal antiinflammatory drugs (NSAIDs) should
use ginger with caution, due to a theoretical risk of bleeding resulting from additive pharmacology related to the COX enzymes.
However, clinical documentation of interactions is lacking. Several pungent constituents of ginger (Zingiber officinale) are
reported to inhibit arachidonic acid (AA) induced platelet activation in human whole blood. The constituent (8)-paradol is the
most potent inhibitor of COX-1 and exhibits the greatest anti-platelet activity versus other gingerol analogues. The mechanism
of ginger-associated platelet inhibition may be related to decreased COX-1/Thomboxane synthase enzymatic activity. 28470 29960
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and
NSAIDs as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet
aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug
therapy. 25082 25083 25273 28470 41251 41258 41265

Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which
indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents,
patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between
sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and
sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful
patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose
adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in
patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. 24711 29374 51000

glipiZIDE: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which
indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents,
patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between
sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and
sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful
patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose
adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in
patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. 24711 29374 51000
glipiZIDE; metFORMIN: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin
synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral
antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant
interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide
metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic
activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A
sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug
combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood
concentrations. 24711 29374 51000
glyBURIDE: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis, which
indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic agents,
patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction between
sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and
sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful
patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose
adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in
patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. 24711 29374 51000

glyBURIDE; metFORMIN: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin
synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral
antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant
interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide
metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic
activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A
sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug
combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood
concentrations. 24711 29374 51000

Gold: (Moderate) Due to the inhibition of renal prostaglandins by NSAIDs, concurrent use with other nephrotoxic agents, such
as gold compounds, may lead to additive nephrotoxicity. Monitor renal function carefully during concurrent therapy. 30110 30268

guanFACINE: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including
renal and peripheral vasoactive pathways. 805

H2-blockers: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric
pH elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or
more. 32122

Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated
with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include
patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister
IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal
function. 6859 7020 7823
Hydantoins: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. 6112

hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of
diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and
thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492

hydroCHLOROthiazide, HCTZ; Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492

HYDROcodone; Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Hydrocortisone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Avoid concomitant use of naproxen with
phenyl salicylate due to an increased risk of gastrointestinal toxicity and renal impairment, with little or no increase in efficacy.
32122 61171

Ibandronate: (Moderate) Monitor renal function and for gastrointestinal adverse events during concurrent use of intravenous or
oral ibandronate, respectively, and nonsteroidal antiinflammatory drugs. Acute renal failure has been observed with intravenous
ibandronate and concomitant use of other nephrotoxic agents may increase this risk. Additionally, the oral formulations of both
medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little
additional risk for adverse effects for most patients. 29558 31826

Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with
drugs that interfere with platelet function such as nonsteroidal antiinflammatory drugs (NSAIDs); the risk of bleeding may be
increased. If coadministration with NSAIDs is necessary, monitor platelet counts more frequently for evidence of
thrombocytopenia. 41826 (Moderate) Monitor serum potassium concentrations closely if potassium supplements and
nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272
53793

Ibuprofen lysine: (Major) Because ibuprofen lysine exerts similar pharmacologic characteristics to other systemic NSAIDs,
including COX-2 inhibitors, additive pharmacodynamic effects, including a potential increase for additive adverse GI effects,
may be seen if ibuprofen lysine is used with other NSAIDs. In general, concurrent use of ibuprofen lysine and another NSAID
should be avoided. 30115 30569

Ibuprofen: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious NSAID toxicities
including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Ibuprofen; Famotidine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893 (Moderate) Avoid
concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH elevating effects of H2-
blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more. 32122

Ibuprofen; oxyCODONE: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Ibuprofen; Pseudoephedrine: (Major) Avoid concomitant use of ibuprofen with any other NSAID due to the risk of additive serious
NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 35893

Iloprost: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal
dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients
receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG
products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal
function. 6859 7020 7823

Indapamide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some
patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood
flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight
gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a
diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic
efficacy. 24233 30489 48492

Indomethacin: (Major) Avoid concomitant use of indomethacin with any other NSAID, including COX-2 inhibitors, due to the risk
of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 32122 45886

Inotersen: (Moderate) Use caution with concomitant use of inotersen and nonsteroidal antiinflammatory drugs (NSAIDs) due to
the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider
discontinuation of NSAIDs in a patient taking inotersen with a platelet count of less than 50,000 per microliter. 63624

Iodine; Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and
nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272
53793

Iodixanol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702
Iohexol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Iomeprol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when
given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent.
28692

Iopamidol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Iopromide: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Ioversol: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Irbesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Irbesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Isosulfan Blue: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity when given to
patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast agent. 28692
28702

Isradipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such
as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased
exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. 34493 48524

Ketoprofen: (Major) Avoid concomitant use of ketoprofen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30548 32122

Ketorolac: (Contraindicated) Concomitant use of ketorolac with another NSAID is contraindicated. Increased adverse
gastrointestinal effects are possible if ketorolac is used with other systemic nonsteroidal antiinflammatory drugs (NSAIDs). 28331
32122

Labetalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

lamiVUDine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a
nephrotoxic agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure,
some requiring hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were
initiated in patients who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction.
If these drugs must be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose,
and urine protein prior to, and periodically during, treatment. 28193 30268

Leflunomide: (Moderate) In vitro studies indicate that the M1 metabolite of leflunomide inhibits cytochrome P450 2C9, the
enzyme responsible for the metabolism of many NSAIDs. Leflunomide altered protein binding and thus, increased the free
fraction of ibuprofen by 13% to 50%. The clinical significance of the interactions with NSAIDs is unknown. There was extensive
concomitant use of NSAIDs in phase III clinical studies of leflunomide in the treatment of rheumatoid arthritis, and no clinical
differential effects were observed. However, because some NSAIDs have been reported to cause hepatotoxic effects, some caution
may be warranted in their use with leflunomide. 49634
Levamlodipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently
used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Levobunolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

levoFLOXacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Levomefolate: (Minor) L-methylfolate should be used cautiously in patients taking high doses of naproxen. Plasma concentrations
of L-methylfolate may be reduced when used concomitantly with high doses of naproxen. Monitor patients for decreased
efficacy of L-methylfolate if these agents are used together. 35581

Levomilnacipran: (Moderate) Platelet aggregation may be impaired by SNRIs such as levomilnacipran due to platelet serotonin
depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis,
hematomas, petechiae, hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and
symptoms of bleeding in patients taking levomilnacipran and NSAIDs. 55469

Lisinopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Lisinopril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492

Lithium: (Moderate) Monitor serum lithium concentrations during concomitant nonsteroidal anti-inflammatory (NSAID) use;
reduce the lithium dose based on serum lithium concentrations and clinical response. NSAIDs decrease renal blood flow,
resulting in decreased renal clearance and increased serum lithium concentrations. 54241

Lomustine, CCNU: (Major) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of
bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA,
strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause
hypoprothrombinemia, an additional risk factor for bleeding. 5170 7668

Losartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Losartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen
and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered
together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce
and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to
decreased efficacy or increased or prolonged therapeutic effects and adverse events. 34993 34995 59891 (Minor) Increased
monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as naproxen. In vitro
studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9
substrates; however, the clinical impact of this has not yet been determined. 34493 48524

Lumacaftor; Ivacaftor: (Moderate) Although the clinical significance of this interaction is unknown, concurrent use of naproxen
and lumacaftor; ivacaftor may alter naproxen exposure; caution and monitoring are advised if these drugs are administered
together. Naproxen is a substrate of CYP2C9 (primary) and CYP2C8. In vitro data suggest that lumacaftor; ivacaftor may induce
and/or inhibit CYP2C8 and CYP2C9. The net effect on these substrates is not clear, but their exposure may be affected leading to
decreased efficacy or increased or prolonged therapeutic effects and adverse events. 34993 34995 59891

Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as
nonsteroidal antiinflammatory drugs (NSAIDs). Healthcare providers are advised to discontinue NSAID therapy and observe a
sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the
macimorelin growth hormone test. 62723

Mafenide: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. 6112

Magnesium Hydroxide: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid
use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2
hours. 6112 8934

Magnesium Salicylate: (Major) Avoid concomitant use of naproxen with magnesium salicylate due to an increased risk of
gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171

Magnesium Salts: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use
should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
6112 8934

Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in
patients taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs).
41573

Mannitol: (Major) Avoid use of mannitol and nonsteroidal anti-inflammatory drugs (NSAIDs), if possible. If use together is
necessary, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Concomitant
administration of nephrotoxic drugs, such as NSAIDs, increases the risk of renal failure after administration of mannitol.
NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of
prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood
pressure that are often accompanied by peripheral edema and weight gain. 30489 33007 48492
Mecamylamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently
used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Mechlorethamine, Nitrogen Mustard: (Major) Mechlorethamine, nitrogen mustard is highly toxic and is associated with
lymphocytopenia, granulocytopenia, and thrombocytopenia. Due to the thrombocytopenic effects of mechlorethamine, an
additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including
aspirin, ASA, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause
hypoprothrombinemia, an additional risk factor for bleeding. 5170 7997

Meclofenamate Sodium: (Major) Avoid concomitant use of meclofenamate sodium with any other NSAID, including COX-2
inhibitors, due to the risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or
peptic ulcers. 30574 32122

Mefenamic Acid: (Major) Avoid concomitant use of mefenamic acid with any other NSAID, including COX-2 inhibitors, due to the
risk of additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30570 32122
Meloxicam: (Major) Avoid concomitant use of meloxicam with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 29611 32122

Mesalamine, 5-ASA: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-
inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity. 11423

Methenamine; Sodium Salicylate: (Major) Avoid concomitant use of naproxen with sodium salicylate due to an increased risk of
gastrointestinal toxicity and renal impairment, with little or no increase in efficacy. 32122 61171

Methotrexate: (Major) Do not administer nonsteroidal anti-inflammatory drugs (NSAIDs) before or concomitantly with high
doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high
dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths
from severe hematologic and gastrointestinal toxicity. Use caution when NSAIDs are administered concomitantly with lower
doses of methotrexate as they have been reported to reduce the tubular secretion of methotrexate in an animal model and may
enhance its toxicity. Despite potential interactions, patients with rheumatoid arthritis (RA) are often receiving concurrent
treatment with NSAIDs without apparent problems. However, these doses are lower than those used in psoriasis or malignancy;
higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. NSAIDs may be continued in patients
with RA receiving treatment with methotrexate, although the possibility of increased toxicity has not been fully explored. 56263
57771 60517 61900 66594

Methoxsalen: (Minor) Preclinical data suggest agents that inhibit prostaglandin synthesis such as naproxen could decrease the
efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of naproxen before and during photodynamic
therapy may be advisable. 6625

Methyldopa: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

methylPREDNISolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Methylsulfonylmethane, MSM: (Moderate) Patients taking methylsulfonylmethane, MSM have reported increased bruising or blood
in the stool. These effects have not been confirmed in published medical literature or during clinical studies. Use
methylsulfonylmethane, MSM with caution in patients who are taking drugs with the potential for additive bleeding, including
nonsteroidal antiinflammatory drugs (NSAIDs). During an available, published clinical trials in patients with osteoarthritis,
patients with bleeding disorders or using anticoagulants or platelet inhibiting drugs were excluded from enrollment. Patients
who choose to consume methylsulfonylmethane, MSM while receiving NSAIDs should be observed for potential bleeding. 32984
32986

metOLazone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use.
NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide
diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. 35893 48492

Metoprolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Metoprolol; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and
loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID)
and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory
drug (NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

miFEPRIStone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction
studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with
coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be
monitored closely for adverse reactions. 48697

Milnacipran: (Moderate) Platelet aggregation may be impaired by milnacipran due to platelet serotonin depletion, possibly
increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae,
hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor for signs and symptoms of bleeding
in patients taking milnacipran and NSAIDs. 28275 29934
mitoXANTRONE: (Major) Due to the thrombocytopenic effects of mitoxantrone, an additive risk of bleeding may be seen in
patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. 41139

Moexipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325
Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Moxifloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Nabumetone: (Major) Avoid concomitant use of nabumetone with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 31941 32122

Nadolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Nebivolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Nelarabine: (Major) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 8493

Neomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other
nephrotoxic agents, such as aminoglycosides. 5046 5062

Neostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Neostigmine; Glycopyrrolate: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors,
leading to gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of
active or occult gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow
inflammatory neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data
at this time to suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

NiCARdipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

NIFEdipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

niMODipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Nisoldipine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Nizatidine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH
elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
32122

Non-Ionic Contrast Media: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk for nephrotoxicity
when given to patients receiving a contrast agents. When possible, withhold NSAID therapy during administration of a contrast
agent. 28692 28702

Ofloxacin: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

OLANZapine; FLUoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin
reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin
release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between
use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414
32127

Olmesartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Olmesartan; amLODIPine; hydroCHLOROthiazide, HCTZ: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an
antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and
blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent
NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in
patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction
in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in
blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to
maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk
of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related
decreases in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate)
Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-
inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In
persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and
NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible.
27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of
diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and
thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492

Olmesartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Olopatadine; Mometasone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and nonsteroidal antiinflammatory drugs (NSAIDs) when the
platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding. 52213

Omeprazole; Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic
antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at
least 2 hours. 6112 8934

Oritavancin: (Moderate) Naproxen is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may
result in elevated naproxen plasma concentrations. If these drugs are administered concurrently, monitor patients for NSAID-
induced toxicity, such as nausea, GI bleeding, or renal dysfunction. 11351 11353 57741

Oxaprozin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30565 32122

PACLitaxel: (Major) Due to the thrombocytopenic effects of paclitaxel, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5938

Pamidronate: (Moderate) Monitor renal function during concomitant pamidronate and nonsteroidal antiinflammatory drug use
due to risk for additive nephrotoxicity. 31027 32122

PARoxetine: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127

Pentamidine: (Major) Avoid concurrent or sequential use of pentamidine with naproxen. Coadministration may increase the risk
for drug-induced nephrotoxicity. Closely monitor renal function if coadministration is unavoidable. 28879

Pentosan: (Moderate) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946
Pentostatin: (Major) Due to the thrombocytopenic effects of pentostatin, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5170 5512

Perindopril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Perindopril; amLODIPine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal
anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons
who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may
result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 32122 61325

Phenoxybenzamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently
used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Phentolamine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Phenytoin: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with hydantoins, monitor patients for toxicity from either drug. 6112

Photosensitizing agents (topical): (Moderate) Agents that inhibit prostaglandin synthesis such as nonsteroidal antiinflammatory
drugs (NSAIDs), could decrease the efficacy of photosensitizing agents used in photodynamic therapy. Avoidance of NSAIDs
before and during photodynamic therapy may be advisable. 42968

PHYSostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Pindolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Pioglitazone; Glimepiride: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin
synthesis, which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral
antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant
interaction between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide
metabolite, and sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic
activity. Careful patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A
sulfonylurea dose adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug
combination is used in patients with renal impairment or other metabolic defects that might increase sulindac blood
concentrations. 24711 29374 51000

Piroxicam: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 29613 32122

Platelet Inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as nonsteroidal antiinflammatory
drugs (NSAIDS), may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study
conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic
oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and
then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the
third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for
treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic
acetaminophen. 39165

Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking
concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). 41573

Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients
taking concomitant medications that may affect renal function such as nonsteroidal anti-inflammatory drugs (NSAIDs). 41573

Polymyxin B: (Major) The chronic coadministration of systemic polymyxins may increase the risk of developing nephrotoxicity,
even in patients who have normal renal function. Nonsteroidal antiinflammatory drugs (NSAIDs) may increase the risk for
nephrotoxicity when used concurrently. Monitor patients for changes in renal function if these drugs are coadministered. Since
Polymyxin B is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including nonsteroidal
antiinflammatory drugs (NSAIDs), may theoretically increase serum concentrations of either drug. 28447

Potassium Acetate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-
inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium Bicarbonate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal
anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal
anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium Citrate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-
inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium Citrate; Citric Acid: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and
nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272
53793
Potassium Gluconate: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal
anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium Iodide, KI: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal
anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

Potassium: (Moderate) Monitor serum potassium concentrations closely if potassium supplements and nonsteroidal anti-
inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of hyperkalemia. 30272 53793

PRALAtrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant
administration of drugs that undergo substantial renal clearance, such as nonsteroidal antiinflammatory drugs (NSAIDs), may
result in delayed clearance of pralatrexate. 36890
Prasugrel: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Prazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

prednisoLONE: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

predniSONE: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Probenecid: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following
concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life
increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's
glucuronide metabolite as well as inhibition of renal clearance. 23583 29374

Probenecid; Colchicine: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following
concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life
increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's
glucuronide metabolite as well as inhibition of renal clearance. 23583 29374

Procarbazine: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic
agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for
bleeding. 5170 5356

Propranolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

pyRIDostigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344

Quinapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Quinapril; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive
effect of ACE inhibitors may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised
renal function, coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible
acute renal failure; these effects are usually reversible. 32122 61325 (Moderate) Monitor blood pressure as well as for signs of
worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal
antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow,
which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs
have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt
the cardiovascular effects of diuretics. 35893 48492
Quinolones: (Moderate) Use quinolones and nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with caution due to
potential increased risk of CNS stimulation and convulsive seizures. NSAIDs in combination with very high doses of quinolones
have been shown to provoke convulsions in preclinical studies and postmarketing. 28423 28424 28764 29947 43411 65562

Ramipril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

raNITIdine: (Moderate) Avoid concomitant use of enteric-coated, delayed-release naproxen and H2-blockers due to the gastric pH
elevating effects of H2-blockers. Enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or more.
32122

Reteplase, r-PA: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these
pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving
these drugs concurrently should be monitored closely for bleeding. 28469 30569

Risedronate: (Minor) Monitor for gastrointestinal adverse events during concurrent use of risedronate and nonsteroidal
antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest
concomitant use introduces little additional risk for adverse effects for most patients. 42080

Rivaroxaban: (Major) An additive risk of bleeding may be seen in patients receiving anticoagulants in combination with other
agents known to increase the risk of bleeding such as nonsteroidal antiinflammatory drugs (NSAIDs). Monitor clinical and
laboratory response closely during concurrent use. 29732 40621 49946

Rivastigmine: (Moderate) NSAIDs may cause additive pharmacodynamic GI effects with cholinesterase inhibitors, leading to
gastrointestinal intolerance. Patients receiving concurrent NSAIDs should be monitored closely for symptoms of active or occult
gastrointestinal bleeding. While NSAIDs appear to suppress microglial activity, which in turn may slow inflammatory
neurodegenerative processes important for the progression of Alzheimer's disease (AD), there are no clinical data at this time to
suggest that NSAIDs alone or as combined therapy with AD agents result in synergistic effects in AD. 27344
Sacubitril; Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II
blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be
diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of
angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these
effects are usually reversible. 27388 27991 28608 29130 32122 60860

Salsalate: (Major) Avoid concomitant use of naproxen with salsalate due to an increased risk of gastrointestinal toxicity and renal
impairment, with little or no increase in efficacy. 32122 61171

Selective serotonin reuptake inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective
serotonin reuptake inhibitor (SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding.
Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association
between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding.
27414 32127

Sertraline: (Moderate) Monitor for signs and symptoms of bleeding during concomitant selective serotonin reuptake inhibitor
(SSRI) and nonsteroidal antiinflammatory drug (NSAID) use due to increased risk for bleeding. Serotonin release by platelets
plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic
drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. 27414 32127
Sodium Bicarbonate: (Minor) Concomitant administration of antacids can delay the absorption of naproxen. Periodic antacid use
should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
6112 8934

Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with
potential to alter renal perfusion or function such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of
acute phosphate nephropathy in patients taking sodium phosphate monobasic monohydrate; sodium phosphate dibasic
anhydrous. 32159 32160

Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate;
magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as
nonsteroidal anti-inflammatory drugs (NSAIDs). 51258

Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Monitor serum potassium concentrations closely if potassium
supplements and nonsteroidal anti-inflammatory drugs (NSAIDs) are used together. Concomitant use may increase the risk of
hyperkalemia. 30272 53793

Sotalol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Sparsentan: (Moderate) Monitor for worsening renal function during concomitant use of sparsentan and nonsteroidal
antiinflammatory drugs (NSAIDs), including selective cyclooxygenase (COX-2) inhibitors. Concomitant use increases the risk for
nephrotoxicity, especially in patients with additional risk factors such as hypovolemia and chronic renal impairment. 68641
Spironolactone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory drug (NSAID) use.
NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the
cardiovascular effects of diuretics. 32018 48492

Spironolactone; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function
and loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug
(NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate
overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to
reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular
effects of diuretics. 35893 48492 (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of
diuretic efficacy, including antihypertensive effects, during concomitant spironolactone and nonsteroidal antiinflammatory
drug (NSAID) use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention
which may blunt the cardiovascular effects of diuretics. 32018 48492

Streptomycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-
inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as streptomycin. 28370 30110 30268

Sucralfate: (Moderate) Separate sucralfate and naproxen administration by at least 2 hours. Concomitant administration of
sucralfate and enteric-coated or delayed-release naproxen tablets can delay the absorption of naproxen. 29374 32122

sulfADIAZINE: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. 6112

Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may
displace other highly protein bound drugs from albumin or vice versa. If naproxen is used concurrently with sulfonamides,
monitor patients for toxicity from either drug. 6112

sulfaSALAzine: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. 6112

Sulfonamides: (Minor) Naproxen is 99% bound to albumin. Thus, naproxen may displace other highly protein bound drugs from
albumin or vice versa. If naproxen is used concurrently with sulfonamides, monitor patients for toxicity from either drug. 6112

Sulfonylureas: (Moderate) NSAIDs may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis,
which indirectly increases insulin secretion. If NSAIDs are administered or discontinued in patients receiving oral antidiabetic
agents, patients should be monitored for hypoglycemia or loss of blood glucose control. No clinically significant interaction
between sulindac at daily doses of 400 mg and oral hypoglycemic agents has been observed. Sulindac, its sulfide metabolite, and
sulfonylureas are highly bound to protein. Sulindac could displace the sulfonylureas, altering hypoglycemic activity. Careful
patient monitoring is recommended to ensure that no change in their diabetes medicine dosage is required. A sulfonylurea dose
adjustment may be needed, especially if sulindac doses greater than 400 mg daily are used or if the drug combination is used in
patients with renal impairment or other metabolic defects that might increase sulindac blood concentrations. 24711 29374 51000

Sulindac: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 28340 32122

Tacrolimus: (Moderate) Monitor patients for signs of worsening renal function during coadministration of tacrolimus and
nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. 28611

Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as nonsteroidal
antiinflammatory drugs (NSAIDS) may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin
doses based on calculated creatinine clearance. 36615 7020

Telmisartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Telmisartan; amLODIPine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin II blocker and nonsteroidal anti-inflammatory drug
(NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by NSAIDs. In persons who are elderly,
volume-depleted, or with compromised renal function, coadministration of angiotensin II blockers and NSAIDs may result in
deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 27388 27991 28608 29130
32122 60860

Telmisartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Temozolomide: (Major) Myelosuppression, primarily neutropenia and thrombocytopenia, is the dose-limiting toxicity of
temozolomide. Due to the thrombocytopenic effects of temozolomide, an additive risk of bleeding may be seen in patients
receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, ASA, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. 5170 7578

Tenecteplase: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these
pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving
these drugs concurrently should be monitored closely for bleeding. 28469 30569

Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination
with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys
by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug
that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally
eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269 60688

Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination
with nephrotoxic agents, such as nonsteroidal antiinflammatory drugs (NSAIDs). Tenofovir is primarily excreted via the kidneys
by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug
that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally
eliminated drugs, thus, increasing the risk of adverse reactions. 30268 60269 60688

Tenofovir Disoproxil Fumarate: (Moderate) Avoid administering tenofovir, PMPA concurrently with or recently after a nephrotoxic
agent, such as high-dose or multiple nonsteroidal antiinflammatory drugs (NSAIDs). Cases of acute renal failure, some requiring
hospitalization and renal replacement therapy, have been reported after high-dose or multiple NSAIDs were initiated in patients
who appeared stable on tenofovir. Consider alternatives to NSAIDs in patients at risk for renal dysfunction. If these drugs must
be coadministered, carefully monitor the estimated creatinine creatinine, serum phosphorus, urine glucose, and urine protein
prior to, and periodically during, treatment. 28193 30268

Terazosin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Teriflunomide: (Moderate) Increased monitoring is recommended if teriflunomide is administered concurrently with CYP2C8
substrates, such as naproxen. In vivo studies demonstrated that teriflunomide is an inhibitor of CYP2C8. Coadministration may
lead to increased exposure to CYP2C8 substrates; however, the clinical impact of this has not yet been determined. Monitor for
increased adverse effects, including additive hepatotoxicity. 51794

Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9
substrates, such as naproxen. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to
increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined. 34493 48524

Thiazide diuretics: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use.
NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of thiazide
diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. 35893 48492

Thioguanine, 6-TG: (Major) Due to the thrombocytopenic effects of thioguanine, an additive risk of bleeding may be seen in
patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and
thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk
factor for bleeding. 5170 5853
Thrombolytic Agents: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these
pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving
these drugs concurrently should be monitored closely for bleeding. 28469 30569

Ticagrelor: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Timolol: (Moderate) Monitor blood pressure during concomitant beta-blocker and nonsteroidal anti-inflammatory drug (NSAID)
use. The antihypertensive effect of beta-blockers may be diminished by NSAIDs. 32122

Tirofiban: (Moderate) Monitor for signs and symptoms of bleeding during concomitant platelet inhibitor and chronic
nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of bleeding. 28435 36055

Tobacco: (Major) Advise patients to avoid smoking tobacco while taking nonsteroidal anti-inflammatory drugs (NSAIDs).
Concomitant use of NSAIDs with tobacco smoking may enhance the risk of gastrointestinal side effects, including peptic ulcer
and GI bleeding. Patients using tobacco and NSAIDs concurrently should be monitored closely for GI adverse reactions. 28327
30496 32018 56268

Tobramycin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-
inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as tobramycin. 28370 30110 30268

Tolmetin: (Major) Avoid concomitant use of naproxen with any other NSAID, including COX-2 inhibitors, due to the risk of
additive serious NSAID toxicities including but not limited to GI bleeding, GI perforation, or peptic ulcers. 30242 32122

Torsemide: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor
the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs
concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some
patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood
flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight
gain. 30489 48492

Trandolapril: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin-converting
enzyme (ACE) inhibitor and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors
may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of ACE inhibitors and NSAIDs may result in deterioration of renal function, including possible acute renal
failure; these effects are usually reversible. 32122 61325

Trandolapril; Verapamil: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are
concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control.
Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying
degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489 (Moderate) Monitor blood
pressure and renal function periodically during concomitant angiotensin-converting enzyme (ACE) inhibitor and nonsteroidal
anti-inflammatory drug (NSAID) use. The antihypertensive effect of ACE inhibitors may be diminished by NSAIDs. In persons
who are elderly, volume-depleted, or with compromised renal function, coadministration of ACE inhibitors and NSAIDs may
result in deterioration of renal function, including possible acute renal failure; these effects are usually reversible. 32122 61325

traZODone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly
increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae,
hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Patients should be instructed to monitor for
signs and symptoms of bleeding while taking trazodone concurrently with medications that impair platelet function and to
promptly report any bleeding events to the practitioner. 38831

Treprostinil: (Moderate) NSAIDs may decrease the effect of antihypertensive agents through various mechanisms, including renal
and peripheral vasoactive pathways. 4087

Triamcinolone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal
antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. 24574 29611 35893

Triamterene: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy,
including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory drugs
(NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and
concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the
cardiovascular effects of diuretics. 32122 48492

Triamterene; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and
loss of diuretic efficacy, including antihypertensive effects, during concomitant nonsteroidal antiinflammatory drug (NSAID)
and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal
decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the
natriuretic effect of thiazide diuretics and are associated with fluid retention which may blunt the cardiovascular effects of
diuretics. 35893 48492 (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic
efficacy, including antihypertensive effects, during concomitant triamterene and naproxen use. Nonsteroidal antiinflammatory
drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation,
and concomitant diuretic use increases the risk of this reaction. NSAIDs are associated with fluid retention which may blunt the
cardiovascular effects of diuretics. 32122 48492

Urea: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients.
NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow
leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a
diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic
efficacy. 30489 48492

valACYclovir: (Moderate) Monitor patients for signs of worsening renal function during coadministration of valacyclovir and
nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity. 29970 56268

valGANciclovir: (Minor) Concurrent use of nephrotoxic agents, such as NSAIDs, with valganciclovir should be done cautiously to
avoid additive nephrotoxicity. 5193

Valsartan: (Moderate) Monitor blood pressure and renal function periodically during concomitant angiotensin II blocker and
nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II blockers may be diminished by
NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function, coadministration of angiotensin II
blockers and NSAIDs may result in deterioration of renal function, including possible acute renal failure; these effects are
usually reversible. 27388 27991 28608 29130 32122 60860

Valsartan; hydroCHLOROthiazide, HCTZ: (Moderate) Monitor blood pressure and renal function periodically during concomitant
angiotensin II blocker and nonsteroidal anti-inflammatory drug (NSAID) use. The antihypertensive effect of angiotensin II
blockers may be diminished by NSAIDs. In persons who are elderly, volume-depleted, or with compromised renal function,
coadministration of angiotensin II blockers and NSAIDs may result in deterioration of renal function, including possible acute
renal failure; these effects are usually reversible. 27388 27991 28608 29130 32122 60860 (Moderate) Monitor blood pressure as well as
for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant
nonsteroidal antiinflammatory drug (NSAID) and thiazide diuretic use. NSAIDs may cause a dose-dependent reduction in renal
blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction.
NSAIDs have been shown to reduce the natriuretic effect of thiazide diuretics and are associated with fluid retention which may
blunt the cardiovascular effects of diuretics. 35893 48492

Vancomycin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other
nephrotoxic agents, including vancomycin. 28370 28468 30110 30268

Vemurafenib: (Minor) Concomitant use of vemurafenib and naproxen may result in increased naproxen concentrations.
Vemurafenib is a CYP2C9 and CYP1A2 inhibitor and naproxen is a CYP2C9 and CYP1A2 substrate. Patients should be
monitored for toxicity. 11351 11353 45335

Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly
increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae,
hemorrhage) in patients receiving nonsteroidal antiinflammatory drugs (NSAIDs). Monitor patients for signs and symptoms of
bleeding when coadministering venlafaxine with NSAIDs. 28275

Verapamil: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used,
carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of
antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees,
have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent
antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation,
which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are
often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal
perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse
effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases
in renal function and an increased risk of stroke and coronary artery disease. 24233 26486 27388 30489

Verteporfin: (Moderate) Use caution if coadministration of verteporfin with nonsteroidal anti-inflammatory drugs is necessary
due to the risk of decreased verteporfin efficacy. Oxaprozin may additionally worsen photosensitivity. Verteporfin is a light-
activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive
factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease
platelet aggregation like nonsteroidal anti-inflammatory drugs could decrease the efficacy of verteporfin therapy. 30003

Vigabatrina: (menor) La vigabatrina no se metaboliza significativamente; sin embargo, es un inductor del CYP2C9. En teoría, puede producirse
una menor exposición a fármacos que se metabolizan ampliamente por el CYP2C9, como el naproxeno, durante el uso concomitante de
vigabatrina. 36250

Vilazodona: (Moderada) La agregación plaquetaria puede verse afectada por la vilazodona debido a la depleción de serotonina plaquetaria, lo que
posiblemente aumente el riesgo de una complicación hemorrágica (p. ej., hemorragia gastrointestinal, equimosis, epistaxis, hematomas,
petequias, hemorragia) en pacientes que reciben medicamentos antiinflamatorios no esteroides (AINE). Se debe indicar a los pacientes que
controlen los signos y síntomas de sangrado mientras toman vilazodona simultáneamente con AINE y que informen de inmediato al médico
sobre cualquier evento hemorrágico. 43177
Voclosporina: (moderada) El uso concomitante de voclosporina y fármacos antiinflamatorios no esteroides (AINE) puede producir nefrotoxicidad
aditiva. Se debe controlar la toxicidad renal si se requiere el uso concomitante. 66336 66357

Vorapaxar: (moderado) Controlar los signos y síntomas de sangrado durante el uso concomitante de inhibidores plaquetarios y antiinflamatorios
no esteroideos (AINE) crónicos. El uso concomitante aumenta el riesgo de sangrado. 28435 36055

Voriconazol: (moderado) La isoenzima hepática CYP2C9 es responsable del metabolismo de muchos AINE. Se sabe que el voriconazol es un
inhibidor de CYP2C9 y puede provocar un aumento de los niveles plasmáticos de algunos AINE, como el naproxeno. Se desconoce la
importancia clínica de esta posible interacción. Se debe controlar la aparición de efectos secundarios relacionados con los AINE, como retención
de líquidos o irritación gastrointestinal, y ajustar la dosis del AINE si es necesario. 4882

Vortioxetina: (Moderada) La agregación plaquetaria puede verse afectada por la vortioxetina debido a la depleción de serotonina plaquetaria, lo
que posiblemente aumente el riesgo de una complicación hemorrágica (p. ej., hemorragia gastrointestinal, equimosis, epistaxis, hematomas,
petequias, hemorragia) en pacientes que reciben medicamentos antiinflamatorios no esteroides (AINE). Los episodios de sangrado relacionados
con medicamentos que inhiben la recaptación de serotonina han variado desde equimosis hasta hemorragias potencialmente mortales. Se debe
indicar a los pacientes que controlen los signos y síntomas de sangrado mientras toman vortioxetina simultáneamente con medicamentos que
alteran la función plaquetaria y que informen de inmediato al médico sobre cualquier episodio de sangrado. 56041

Warfarina: (moderada) Vigile a los pacientes para detectar signos o síntomas de sangrado durante el uso concomitante de warfarina y
medicamentos antiinflamatorios no esteroides (AINE). Para minimizar la posibilidad de sangrado gastrointestinal, use la dosis efectiva más baja
de AINE durante el menor tiempo posible. Si aparecen signos o síntomas de sangrado, evalúe y trate de inmediato. También pueden ocurrir
efectos hematológicos sistémicos con el uso de AINE tópicos. Los AINE inhiben la agregación plaquetaria y pueden prolongar el tiempo de
sangrado en algunos pacientes. 28549 33554 56268 61088

Ácido zoledrónico: (moderado) Controlar la función renal durante el uso concomitante de ácido zoledrónico y medicamentos antiinflamatorios
no esteroides debido al riesgo de nefrotoxicidad aditiva. 32122 58724

Reacciones adversas

Reacciones adversas

Dolor abdominal visión borrosa diaforesis

acné vulgar fracturas de huesos diarrea

agranulocitosis Dolor de huesos diplopía

alopecia broncoespasmo mareo

ambliopía erupción ampollosa modorra

amnesia bloqueo de rama Reacción a medicamentos con eosinofilia y

síntomas sistémicos (DRESS)
choque anafiláctico Dolor en el pecho (no especificado)
dismenorrea
reacciones anafilactoides escalofríos
dispepsia
anemia colecistitis
disfagia
angina de pecho colelitiasis
dyspnea
angioedema inflamación
disuria
anorexia comer
equimosis
ansiedad confusión
edema
anemia aplásica conjuntivitis
enzimas hepáticas elevadas
exacerbación de la arritmia constipación
labilidad emocional
artralgia dermatitis de contacto
eosinofilia
meningitis aséptica opacificación corneal
epistaxis
astenia tos
eructo
azotemia cistitis
eritema multiforme
Dolor de espalda deshidración
eritema nudoso
sangría depresión
estenosis esofágica insomnio faringitis

ulceración esofágica nefritis intersticial flebitis

esofagitis ictericia fotofobia

dermatitis exfoliativa queratoconjuntivitis fotosensibilidad

fiebre lagrimeo disfunción plaquetaria

dolor en el flanco leucopenia neumonitis

flatulencia erupción parecida al liquen plano poliuria

gastritis síntomas parecidos al lupus tiempo de sangrado prolongado

dar sangrado linfadenopatía proteinuria

Perforación gastrointestinal malestar prurito

glomerulonefritis Dolor de cabeza por uso excesivo de pseudoporfiria

medicamentos
glositis ptosis
melena
glucosuria edema pulmonar
menorragia
alucinaciones púrpura
alcalosis metabólica
dolor de cabeza pirosis (acidez estomacal)
migraña
pérdida de audición piuria
calambres musculares
insuficiencia cardiaca erupción
parálisis muscular
hematemesis Insuficiencia renal (no especificada)
mialgia
hematuria necrosis papilar renal
miastenia
anemia hemolítica depresión respiratoria
infarto de miocardio
insuficiencia hepática rinitis
náuseas
necrosis hepática convulsiones
síndrome nefrótico
hepatitis taquicardia sinusal
neuritis
hepatomegalia sinusitis
nicturia
hipercolesterolemia necrosis de la piel
dolor ocular
hiperglucemia úlcera de la piel
odinofagia
hipercalemia esplenomegalia
oliguria
hipertensión Síndrome de Stevens-Johnson
neuritis óptica
hipertensión estomatitis
ulceración oral
hiperuricemia ataque
palpitaciones
hipoglucemia hematoma subdural
pancreatitis
hipocalemia síncope
pancitopenia
hiponatremia trombocitopenia
edema de papila
hipotensión tromboembolia
parestesias
aumento de la frecuencia urinaria tinnitus
Dolor pélvico
infección necrólisis epidérmica tóxica
úlcera péptica
esterilidad temblor
edema periférico
influenza incontinencia urinaria
vasodilatación periférica
 retención urinaria vértigo retiro

urticaria Discapacidad visual xerosis

vaginitis vómitos xerostomía

vasculitis Pérdida de peso

Las reacciones adversas al naproxeno que se notifican con mayor frecuencia son los efectos adversos gastrointestinales (GI) y pueden ser más
frecuentes con dosis más altas. Los AINE aumentan el riesgo de efectos adversos gastrointestinales graves, como inflamación, sangrado
gastrointestinal , ulceración ( úlcera péptica ) y perforación gastrointestinal (gástrica o intestinal). Estos eventos pueden ser fatales y pueden
ocurrir en cualquier momento durante la terapia. Las úlceras, el sangrado o la perforación gastrointestinales superiores ocurren en
aproximadamente el 1 % de los pacientes tratados durante 3 a 6 meses, y en aproximadamente el 2 % al 4 % de los pacientes tratados durante un
año, y las tendencias continúan con una mayor duración del uso. El estreñimiento , la pirosis (acidez estomacal) , el dolor abdominal y las
náuseas ocurren en el 3 % al 9 % de los pacientes. Se notificó dispepsia en menos del 3 % al 14 % de los pacientes. Se ha producido diarrea en
menos del 3 % al 9 % de los pacientes. La flatulencia , la gastritis , los vómitos , la disfagia y la estomatitis se notifican con menor frecuencia
(menos del 3 %). Los eventos adversos gastrointestinales observados en menos del 1% de los pacientes durante los ensayos con naproxeno
incluyen sangrado gastrointestinal, anorexia , colecistitis , colelitiasis , eructos , hemorragia gastrointestinal, hemorragia rectal, estomatitis
aftosa, estomatitis ulcerosa, ulceración oral , úlcera péptica, absceso periodontal, cardiospasmo, colitis , gastroenteritis, trastorno
gastrointestinal, trastorno rectal, trastorno dental, melena , úlcera esofágica, necrosis y úlcera gastrointestinal no péptica. En pacientes que
toman AINE en general, se notificaron flatulencia, sangrado gastrointestinal, perforación gastrointestinal, úlceras gastrointestinales (gástricas,
duodenales) y vómitos en el 1% al 10%, mientras que se notificaron xerostomía y glositis en menos del 1%. Los eventos gastrointestinales
observados en los informes posteriores a la comercialización incluyen perforación gastrointestinal, hematemesis , colitis, exacerbación de la
enfermedad inflamatoria intestinal (colitis ulcerosa, enfermedad de Crohn), ulceración gastrointestinal no péptica, estomatitis ulcerosa y úlcera
péptica. Los efectos adversos informados por pacientes con artritis reumatoide parecen ser más graves y frecuentes con dosis más altas (1,5 g/día)
que con dosis más bajas (750 mg/día). El sangrado gastrointestinal o la gastritis erosiva pueden ser menores o potencialmente mortales y pueden
ser resultado de una combinación de acción irritante directa sobre la mucosa del estómago y un tiempo de sangrado prolongado , debido a
cambios en la agregación plaquetaria. Pérdida de pesoSe ha informado de efectos adversos en menos del 1% de los pacientes durante los ensayos
clínicos con naproxeno. Se han producido cambios de peso y de apetito en menos del 1% de los pacientes que toman AINE. La incidencia de
eventos gastrointestinales en los ensayos pediátricos fue similar a la de los ensayos con adultos. 32122 44091

Se han reportado casos de esofagitis (< 1%) y ulceración esofágica (< 1%) en pacientes que reciben AINE, como naproxeno. 32122 44091 La
esofagitis inducida por AINE se caracteriza por la aparición repentina de odinofagia , pirosis (acidez estomacal), dolor retroesternal y disfagia. En
raras ocasiones se han notificado complicaciones graves, como ulceración esofágica, estenosis esofágica , sangrado y perforación. Los factores de
riesgo de los efectos esofágicos inducidos por AINE incluyen tomar el medicamento sin agua y por la noche. Los síntomas suelen desaparecer en
cuestión de días o semanas después de suspender el medicamento.

Se ha demostrado que el naproxeno causa disfunción plaquetaria ; este efecto, sin embargo, es transitorio y reversible. Como la inhibición de la
agregación plaquetaria parece correlacionarse con las concentraciones plasmáticas efectivas del fármaco, la semivida individual de cada AINE
determina la duración de este efecto. El glucurónido de naproxeno, un metabolito del naproxeno, puede causar trombocitopenia
inmunomediada . Se observaron hemorragias petequiales generalizadas de 10 a 25 días después del inicio del naproxeno en 3 personas. Los 3
adultos tuvieron una mejoría en sus recuentos de plaquetas de 3 a 8 x 10 9 /L a un rango de concentración normal de 5 a 7 días después de la
interrupción del naproxeno y la recepción de prednisona. Los sueros de cada paciente tenían anticuerpos contra las plaquetas en presencia de
glucurónido de naproxeno. 31419 Se ha observado anemia en menos del 3% de los pacientes durante los ensayos con naproxeno. Otros efectos
hematológicos (menos del 1%) debidos al naproxeno incluyen anemia aplásica , anemia hemolítica , trombocitopenia, tiempo de sangrado
prolongado, glóbulos rojos y blancos anormales, agranulocitosis , leucopenia , eosinofilia y granulocitopenia. Se han observado anemia aplásica,
anemia hemolítica, eosinofilia, leucopenia y granulocitopenia en informes posteriores a la comercialización. Se observaron sangrado rectal,
linfadenopatía y pancitopenia en menos del 1% de los pacientes que tomaban AINE. La pérdida de sangre por daño gastrointestinal causado por
naproxeno generalmente no es significativa. Sin embargo, la pérdida de sangre con el tiempo puede provocar anemia por deficiencia de hierro.
Los pacientes con terapia prolongada deben someterse a un control sanguíneo regular. La interpretación del hematocrito y la hemoglobina debe
considerarse en relación con el estado de los líquidos, ya que el naproxeno puede causar retención de líquidos. 32122 44091

Las reacciones adversas más comunes del sistema nervioso central (SNC) con naproxeno incluyen dolor de cabeza (3% a 15%) y somnolencia (3%
a 9%). Se han notificado casos de vértigo , aturdimiento, parestesias , astenia e insomnio en menos del 3% de los pacientes durante los ensayos
con naproxeno. Se han notificado casos de mareos en menos del 3% al 9% de los pacientes. Otras reacciones del SNC ocurren con menos
frecuencia (menos del 1%), incluyendo depresión , malestar , ansiedad , hipertonía , nerviosismo, neuralgia, neuritis , amnesia , confusión ,
coordinación anormal, diplopía , labilidad emocional , hematoma subdural , parálisis muscular , anomalías del sueño, disfunción cognitiva,
debilidad muscular ( miastenia ) e incapacidad para concentrarse (concentración deteriorada). Los eventos adversos observados en los informes
posteriores a la comercialización incluyen depresión, anomalías del sueño, insomnio, mialgia , debilidad muscular, disfunción cognitiva y
convulsiones . Se observaron somnolencia, temblor , coma y alucinaciones en menos del 1% de los pacientes que tomaban AINE. 32122 44091 El
uso excesivo de medicamentos para tratar los dolores de cabeza agudos, incluidos los AINE, puede provocar un dolor de cabeza por uso excesivo
de medicamentos . Los pacientes pueden experimentar dolores de cabeza diarios similares a la migraña o un aumento significativo en la
frecuencia de los ataques de migraña. Puede ser necesario suspender el medicamento usado en exceso y tratar los síntomas de abstinencia (p. ej.,
empeoramiento transitorio del dolor de cabeza). Informe a los pacientes sobre los riesgos del uso excesivo de medicamentos (p. ej., uso de
naproxeno durante al menos 15 días al mes o cualquier combinación de terapia durante al menos 10 días al mes) y anímelos a mantener un
registro escrito de la frecuencia de los dolores de cabeza y el uso de medicamentos. 66767 66803

Se han notificado alteraciones o deterioros visuales, como visión borrosa , en < 3% de los pacientes que utilizan naproxeno. Otros efectos
adversos oculares notificados en < 1% de los pacientes incluyeron ambliopía , escleritis, cataratas, conjuntivitis , queratoconjuntivitis , trastorno
del lagrimeo y dolor ocular . Se han observado opacificación corneal , papilitis, neuritis óptica retrobulbar y edema de papila en los informes
32122 44091
posteriores a la comercialización. 32122 44091

Durante los ensayos clínicos, se han producido acúfenos (3-9 %), alteraciones auditivas (< 3 %), pérdida de audición /sordera (< 1 %), trastornos
del oído (< 1 %) y otitis media (< 1 %) con naproxeno. Además, se ha observado deterioro auditivo en los informes posteriores a la
comercialización. 32122 44091 Además, se han descrito en la literatura 6 casos de pérdida auditiva. A dos de los 6 pacientes se les realizó un
audiograma posterior al tratamiento, que reveló una pérdida auditiva neurosensorial bilateral grave y permanente. De los otros pacientes, 2 se
recuperaron de su pérdida auditiva y 2 no. 27729 También se han producido acúfenos y pérdida de audición con el uso de los fármacos
antiinflamatorios no esteroides (AINE) piroxicam y ketorolaco. Se cree que la pérdida de audición por el uso de AINE se debe a una alteración de
la función de las células sensoriales cocleares debido a la isquemia tisular como resultado de un desequilibrio entre las prostaglandinas
vasodilatadoras y los leucotrienos vasoconstrictores. 27726 Aunque no se conocen cambios morfológicos conocidos, la pérdida auditiva puede ser
permanente. La administración concomitante de otros fármacos ototóxicos, como la gentamicina o la furosemida, puede aumentar el riesgo de
ototoxicidad. La mayoría de los fármacos ototóxicos tienen interacciones ototóxicas al menos aditivas. Además, los AINE pueden ser nefrotóxicos
y la función renal alterada puede aumentar el potencial ototóxico de los AINE. A los pacientes que toman AINE a largo plazo se les debe
preguntar directamente sobre el tinnitus y la pérdida auditiva.

Se han notificado casos raros de ictericia (< 1%), necrosis hepática (< 1%) y hepatitis mortal o insuficiencia hepática en pacientes que recibieron
naproxeno. Se han notificado casos de hepatoesplenomegalia ( hepatomegalia y esplenomegalia) y pancreatitis en < 1% de los pacientes. Se
producen enzimas hepáticas elevadas en hasta el 15% de los pacientes que reciben AINE. Se han producido elevaciones superiores a tres veces el
límite superior de lo normal en menos del 1% de los pacientes que recibieron naproxeno. Las anomalías de las enzimas hepáticas pueden
progresar, estabilizarse o retroceder con el uso continuo de naproxeno. Las anomalías hepáticas pueden ser el resultado de hipersensibilidad en
lugar de toxicidad directa. Evalúe a los pacientes con signos o síntomas de disfunción hepática, como un resultado anormal en la prueba
hepática, para detectar el desarrollo de una reacción hepática más grave. Se debe suspender el naproxeno si se desarrollan signos o síntomas
clínicos compatibles con enfermedad hepática o si se producen manifestaciones sistémicas como eosinofilia o erupción cutánea . 32122 44091

El naproxeno se ha asociado con meningitis aséptica (incidencia de < 1% en ensayos clínicos), pero no se ha establecido una relación causal.
32122 44091 El ibuprofeno ha sido el AINE más comúnmente implicado en esta reacción adversa; sin embargo, se han reportado casos con
sulindac, tolmetin, diclofenac, ketoprofeno, rofecoxib y piroxicam. La meningitis aséptica por un AINE no excluye el uso de otro AINE; la
mayoría de los pacientes pueden ser tratados con otro fármaco sin incidentes. Sin embargo, un paciente con síndrome de Sjögren experimentó
meningitis aséptica después de recibir naproxeno, ibuprofeno y rofecoxib en diferentes momentos; la meningitis aséptica se desarrolló
aproximadamente una semana después de la exposición a cada fármaco, y los síntomas remitieron aproximadamente 2 días después de la
interrupción de cada fármaco. 27710 La aparición de meningitis aséptica no está relacionada con la clase química de los AINE ni con la
inhibición de las prostaglandinas. El mecanismo de acción propuesto es una reacción de hipersensibilidad inmunológica de tipo III o IV. La
meningitis aséptica inducida por fármacos suele producirse poco después de iniciar el tratamiento con el fármaco, pero puede producirse tras
años de uso del mismo. Aunque la meningitis aséptica inducida por AINE se notifica principalmente en pacientes con lupus eritematoso
sistémico (LES), los pacientes sanos y los pacientes con otras enfermedades, como espondilitis anquilosante, enfermedad del tejido conectivo,
osteoartritis y artritis reumatoide, han desarrollado meningitis aséptica inducida por AINE. Los síntomas de la meningitis aséptica incluyen
confusión, somnolencia, sensación general de enfermedad, dolor de cabeza intenso, náuseas, rigidez de nuca y fotofobia . Como la meningitis
aséptica es un diagnóstico de exclusión, se debe suspender el fármaco sospechoso y no reiniciarlo a menos que se desee una nueva provocación.

En menos del 1% de los pacientes que recibieron naproxeno se han descrito casos de nefropatía, entre ellos anomalías de la función renal,
nefritis intersticial , síndrome nefrótico , hematuria , glomerulonefritis , hipercalemia , insuficiencia renal (no especificada) y necrosis papilar
renal . En menos del 1% de los pacientes que recibieron AINE se han descrito casos de función renal anormal. Es bien sabido que las
prostaglandinas renales vasodilatadoras y la angiotensina II, un potente vasoconstrictor, actúan en conjunto para mantener el flujo sanguíneo
renal. La inhibición de la síntesis de prostaglandinas por los AINE potencia la reabsorción de agua. Se ha descrito toxicidad renal en pacientes
en los que las prostaglandinas renales tienen un papel compensatorio en el mantenimiento de la perfusión renal. Otros eventos adversos
genitourinarios informados en < 1% de los pacientes incluyen dismenorrea , disuria , nicturia , trastorno de próstata, carcinoma o neoplasia de
mama, incontinencia urinaria , cálculo renal, menorragia , metrorragia, nefroesclerosis, dolor renal ( dolor en el flanco ), piuria , orina anormal,
aumento de la frecuencia urinaria , retención urinaria , espasmo uterino, vaginitis y trastornos menstruales. Se produjo edema en < 1 % a 9% y
se informó edema periférico en < 3% de los pacientes que recibieron naproxeno. Se han informado oliguria , poliuria , proteinuria , glucosuria ,
azotemia y albuminuria en < 1% de los pacientes que recibieron AINE. 32122 44091 Se ha informado de hiponatremia debida a intoxicación por
agua con el uso de AINE. 33608 33609 33610 Se recomienda monitorizar el estado hídrico y la función renal del paciente.

Los AINE, incluido el naproxeno, pueden aumentar el riesgo de tromboembolia cardiovascular grave , infarto de miocardio (<1 %) y accidente
cerebrovascular , que puede ser mortal. Las estimaciones del aumento del riesgo relativo varían entre el 10 y el 50 % o más, según el fármaco y la
dosis estudiados. El riesgo puede aumentar con el aumento de la exposición, medida en dosis o duración. Se ha observado un riesgo
cardiovascular significativo en cuestión de días a semanas tras el inicio del tratamiento con AINE. El aumento relativo de los eventos
trombóticos cardiovasculares con respecto al valor inicial parece ser similar en pacientes con o sin enfermedad cardiovascular o factores de
riesgo de enfermedad cardiovascular; sin embargo, los pacientes con enfermedad cardiovascular conocida o factores de riesgo pueden tener un
mayor riesgo debido a un mayor riesgo inicial de eventos. 59937 Se observó hipertensión en < 3% de los pacientes que tomaron naproxeno en
ensayos clínicos; en general, los AINE pueden provocar una nueva aparición o empeoramiento de la hipertensión, lo que puede contribuir al
aumento de la incidencia de eventos cardiovasculares. Se observaron palpitaciones en < 3% de los pacientes que tomaron naproxeno en ensayos
clínicos. Los eventos adversos observados en < 1% de los pacientes incluyeron edema pulmonar , angina de pecho, enfermedad de la arteria
coronaria, tromboflebitis profunda , vasodilatación periférica , anomalía vascular, exacerbación de la arritmia , bloqueo de rama , ECG anormal,
insuficiencia cardíaca , hemorragia (sangrado), migraña, estenosis aórtica, síncope , vasculitis y taquicardia sinusal . La retención de líquidos
causada por naproxeno puede elevar la presión arterial, especialmente en pacientes con hipertensión. Se ha informado hipotensión en < 1% de
los pacientes que toman AINE. 32122 44091 En adultos (76% blancos, 14% negros) con hipertensión estable (sistólica < 150 mmHg) y función
renal normal, el cambio medio desde el inicio en la presión sistólica promedio de 24 horas fue de -0,8 ± 1,1 mmHg y la presión diastólica fue de
-1 ± 0,6 mmHg después de 6 semanas de naproxeno 500 mg dos veces al día. La presión arterial se midió cada 20 minutos durante el monitoreo
ambulatorio de 24 horas y no se permitieron cambios en los medicamentos antihipertensivos (todos los pacientes tomaron al menos un
inhibidor de la enzima convertidora de angiotensina o un bloqueador del receptor de angiotensina-2). Se obtuvieron hallazgos similares cuando
se midió la presión arterial en una clínica entre las 7 y las 11 de la mañana. De los 101 pacientes, se produjo un aumento de la presión arterial
sistólica de 0 a 10 mmHg en el 37 %, un aumento de 10 a 20 mmHg en el 7 % y un aumento de > 20 mmHg en el 2 %. Además, de 57 pacientes
30756
que tenían una presión arterial sistólica ambulatoria basal < 135 mmHg, 11 tuvieron una lectura de >= 135 mmHg en la semana 6. 30756
Informar a los pacientes sobre los signos y síntomas de eventos CV y ​recomendarles que busquen ayuda médica inmediatamente si se presentan
dichos signos o síntomas.

Los efectos adversos más frecuentes en la piel y los tejidos blandos asociados con el naproxeno incluyen prurito (menos del 1% al 9%),
erupciones cutáneas (3% al 9%), sarpullido (menos del 1% al 9%) y equimosis (3% al 9%). La diaforesis y la púrpura ocurren en menos del 3% de
los pacientes. Otras reacciones dermatológicas ocurren con menos frecuencia (menos del 1%), incluyendo angiodermatitis, herpes simple,
xerosis , úlcera cutánea , acné vulgar , alopecia , dermatitis de contacto , eczema, herpes zóster, trastorno de las uñas, necrosis cutánea , nódulo
subcutáneo, neoplasia cutánea, urticaria , reacción de fotosensibilidad similar a la porfiria cutánea tarda, epidermólisis ampollosa ( sarpullido
ampolloso ) y dermatitis fotosensible. En los informes posteriores a la comercialización se observaron eritema nodoso , erupción fija
medicamentosa, erupción similar al liquen plano , reacción pustulosa y lupus eritematoso sistémico ( síntomas similares al lupus ). 32122 44091
Tres pacientes desarrollaron pseudoporfiria durante el tratamiento con naproxeno de venta libre 400 mg/día 4 a 5 veces por semana para la
osteoartritis durante un período de tiempo no especificado. Los pacientes tenían fragilidad cutánea, formación de ampollas, ampollas tensas y/o
erosiones superficiales predominantemente en las zonas expuestas al sol. Los análisis histológicos fueron compatibles con porfiria, pero las
porfirinas en orina y plasma estaban dentro de los límites normales. Las lesiones cutáneas se resolvieron en un plazo de 1 a 6 meses tras la
interrupción del naproxeno. No se observaron recurrencias durante los 15 a 34 meses de seguimiento. 27624 Pueden ocurrir eventos adversos
graves como necrólisis epidérmica tóxica (menos del 1%), eritema multiforme (menos del 1%), dermatitis exfoliativa (menos del 1% de los
pacientes que toman AINE) y síndrome de Stevens-Johnson (menos del 1%) con naproxeno sin advertencia. Aconseje a los pacientes que
suspendan el medicamento y se comuniquen con su proveedor de atención médica si desarrollan eritema, sarpullido, ampollas o reacciones
cutáneas relacionadas. Se produjeron escalofríos , neumonitis eosinofílica , vasculitis y reacciones anafilactoides , incluido choque anafiláctico y
angioedema, en menos del 1% de los pacientes en ensayos clínicos de naproxeno. Se produjo disnea en el 3% al 9% de los pacientes. 32122
44091

Los eventos adversos musculoesqueléticos que ocurrieron en el 3-9% de los pacientes que tomaron naproxeno en ensayos clínicos incluyeron
dolor de espalda y dolor. Se informaron calambres musculares (piernas), mialgia, artralgia , trastornos articulares y trastornos de tendones en
<3% de los pacientes. Los eventos adversos observados en <1% de los pacientes incluyen trastornos óseos, fracturas óseas espontáneas ,
fibrotendinitis, dolor óseo , ptosis , espasmo muscular general y bursitis. 32122 44091

Se han notificado casos de hiperglucemia y sed en menos del 3% de los pacientes durante los ensayos clínicos con naproxeno. Otros efectos
adversos metabólicos y nutricionales notificados en menos del 1% de los pacientes incluyen hipoglucemia , hipercolesterolemia , alcalosis
metabólica , deshidratación , disminución de la tolerancia a la glucosa, hiperuricemia e hipocalemia . 32122 44091

Los eventos adversos infecciosos informados durante los ensayos con naproxeno incluyen infección general (3% a 9%), infección del tracto
urinario (3% a 9%), síndrome similar a la influenza (10%), cistitis (menos del 3%), absceso (menos del 1%), neumonía (menos del 1%) y
pielonefritis (menos del 1%). Los eventos adversos relacionados con la terapia con AINE y que ocurren en menos del 1% incluyen infección,
sepsis y neumonía. 32122 44091

Los eventos adversos respiratorios que se han observado en los ensayos clínicos con naproxeno incluyen faringitis (3-9%), rinitis (3-9%), sinusitis
(3-9%), bronquitis (< 3%), aumento de la tos (< 3%), asma o broncoespasmo (< 1%), trastorno pulmonar (< 1%), epistaxis (< 1%), dificultad
respiratoria (< 1%) y trastorno respiratorio (< 1%). Se han notificado casos de asma y depresión respiratoria en < 1% de los pacientes que toman
AINE. 32122 44091

Los eventos adversos generales informados durante los ensayos clínicos de naproxeno incluyen fiebre (menos del 3%), lesión o accidente (menos
del 3%), dolor en el pecho (no especificado) (menos del 3%), rigidez de nuca (menos del 1%), dolor de cuello (menos del 1%), agrandamiento del
abdomen (menos del 1%), carcinoma (menos del 1%), celulitis (menos del 1%), síndrome de LE (menos del 1%), trastorno de las membranas
mucosas (menos del 1%) y dolor pélvico (menos del 1%). Se informó muerte en menos del 1% de los pacientes que tomaban AINE. 32122 44091

Los AINE, como el naproxeno, pueden retrasar o prevenir la ruptura de los folículos ováricos mediada por prostaglandinas, que se ha asociado
con infertilidad reversible . Estudios pequeños de mujeres tratadas con AINE demostraron un retraso reversible en la ovulación. Considere la
posibilidad de suspender los AINE en mujeres que tienen dificultades para concebir o que se están sometiendo a una evaluación de infertilidad.
32122 Se ha observado infertilidad femenina en informes posteriores a la comercialización del naproxeno. 32122 44091

Se ha producido una reacción de hipersensibilidad multiorgánica con AINE, llamada reacción medicamentosa con eosinofilia y síntomas
sistémicos (DRESS) . Algunos de estos eventos han sido potencialmente mortales o fatales. La DRESS se presenta típicamente como fiebre,
erupción cutánea y/o linfadenopatía junto con afectación de otros sistemas orgánicos, como hepatitis, nefritis, anomalías hematológicas,
miocarditis o miositis, que a veces se asemeja a una infección viral aguda. A menudo se presenta eosinofilia. Las manifestaciones tempranas,
como fiebre y linfadenopatía, pueden estar presentes sin evidencia de erupción cutánea. Suspenda el AINE en pacientes que presenten dichos
signos y síntomas en los que no se pueda identificar una etiología alternativa. 32122

Administración

Información de administración general

Para obtener información sobre el almacenamiento, consulte la información específica del producto en la sección Cómo se suministra.

Administración específica de la ruta

Administración oral
 Administrar con leche, alimentos o antiácidos (preferiblemente antiácidos que contengan hidróxido de aluminio y magnesio)
para minimizar la irritación gastrointestinal. Para automedicarse, administrar con un vaso lleno de agua u otro líquido.

Formulaciones sólidas orales

Tabletas de liberación retardada de EC-Naprosyn: No romper, triturar ni masticar.

Formulaciones líquidas orales

Suspensión oral: Agítese bien antes de usar. Administre utilizando el vaso dosificador provisto u otro dispositivo calibrado
adecuado para la administración precisa de medicamentos líquidos.

Mecanismo de acción

Mechanism of Action: Naproxen competitively inhibits both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, by blocking
arachidonate binding resulting in analgesic, antipyretic, and anti-inflammatory pharmacologic effects. The enzymes COX-1 and
COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), the first step of the synthesis prostaglandins and
thromboxanes that are involved in rapid physiological responses. COX isoenzymes are also responsible for a peroxidase
reaction, which is not affected by NSAIDs. In addition, NSAIDs do not suppress leukotriene synthesis by lipoxygenase pathways.
COX-1 is constitutively expressed in almost all tissues, while COX-2 appears to only be constitutively expressed in the brain,
kidney, bones, reproductive organs, and some neoplasms (e.g., colon and prostate cancers). COX-1 is responsible for
prostaglandin synthesis in response to stimulation by circulating hormones, as well as maintenance of normal renal function,
gastric mucosal integrity, and hemostasis. However, COX-2 is inducible in many cells in response to certain mediators of
inflammation (e.g., interleukin-1, tumor necrosis factor, lipopolysaccharide, mitogens, and reactive oxygen intermediates).

•Anti-inflammatory Activity: The anti-inflammatory mechanism of naproxen is due to decreased prostaglandin synthesis via
inhibition of COX-1 and COX-2. It appears that the anti-inflammatory effects may be primarily due to inhibition of the COX-2
isoenzyme. However, COX-1 is expressed at some sites of inflammation. COX-1 is expressed in the joints of rheumatoid arthritis
or osteoarthritis patients, especially the synovial lining, and it is the primary enzyme of prostaglandin synthesis in human
bursitis. Naproxen is slightly more selective for COX-1 than COX-2.

•Analgesic Activity: Naproxen is effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It
appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore,
naproxen has an indirect analgesic effect by inhibiting the production of further prostaglandins and does not directly affect
hyperalgesia or the pain threshold.

•Antipyretic Activity: Naproxen promotes a return to a normal body temperature set point in the hypothalamus by suppressing
the synthesis of prostaglandins, specifically PGE2, in circumventricular organs in and near the hypothalamus. Naproxen may
mask fever in some patients, especially with high or chronic dosing.

•GI Effects: Gastrointestinal side effects of naproxen are primarily contributed to COX-1 inhibition; however, potential role of
COX-2 inhibition in the GI tract has not been fully elucidated.

• Efectos plaquetarios: La inhibición de la agregación plaquetaria observada con naproxeno se debe a la inhibición dependiente de la dosis de la
COX-1 en las plaquetas, lo que conduce a una disminución de los niveles de tromboxano A2 plaquetario y a un aumento del tiempo de sangrado
(ver Reacciones adversas). La inhibición de la agregación plaquetaria es reversible al suspender el naproxeno. Esto difiere de la aspirina, que se
une irreversiblemente a la COX-1 en las plaquetas inhibiendo esta enzima durante la vida de la célula. En un estudio in vitro , el naproxeno
inhibió la producción de tromboxano y la agregación plaquetaria en un 88% durante hasta 8 horas. El naproxeno inhibió la COX-1 (medida
como la generación de tromboxano B2 en la sangre completa en coagulación) en mayor medida en comparación con el ibuprofeno, el
diclofenaco o el meloxicam (94,9%, 88,7%, 49,5% y 53,3%, respectivamente). 27346 En términos clínicos, el naproxeno puede brindar algunos
beneficios cardioprotectores. Sin embargo, produce una inhibición menos consistente del tromboxano A2 que la aspirina en dosis bajas y, en los
ensayos clínicos, los efectos cardioprotectores del naproxeno han sido inconsistentes.

• Efectos renales: En el riñón, las prostaglandinas, producidas tanto por la COX-1 como por la COX-2, son importantes reguladores de la
reabsorción de sodio y agua a través de la PGE2 y de la función renal y la hemodinámica a través de la PGI2 en respuesta a factores
vasoconstrictores (p. ej., endotelina-1, un factor que aumenta la resistencia vascular periférica) y a través de efectos sobre el sistema renina-
angiotensina. En condiciones en las que el flujo sanguíneo renal depende de la síntesis de prostaglandinas, la administración de AINE puede
producir disminuciones significativas del flujo sanguíneo renal que conducen a insuficiencia renal aguda. Además, las alteraciones en la
reabsorción de sodio y agua pueden empeorar el aumento de la presión arterial, que puede ser significativo en individuos seleccionados.

• Efectos óseos: Los fármacos antiinflamatorios no esteroides parecen suprimir la formación ósea a través de la inhibición de la COX-2. Los datos
in vivo de conejos revelaron una reducción significativa del crecimiento óseo con naproxeno y rofecoxib en comparación con placebo. La
resorción ósea no parece ser un mecanismo que conduzca a una menor formación ósea neta, ya que la cantidad de células similares a
osteoclastos CD51 positivas por sección disminuyó con cualquiera de los AINE en comparación con el agua potable sola. 32351 Según lo
determinado a partir de datos in vitro , los AINE parecen detener el ciclo celular de los osteoblastos en la fase G(0)/G(1) e inducir citotoxicidad y
muerte celular de los osteoblastos principalmente por apoptosis en lugar de por necrosis. 32352
Farmacocinética

El naproxeno se administra por vía oral. Se une a la albúmina en más del 99%. En dosis superiores a 500 mg/día, se produce un aumento menos
que proporcional de las concentraciones plasmáticas debido al aumento de la depuración por saturación de la unión a las proteínas plasmáticas.
Se metaboliza ampliamente en el hígado a 6-O-desmetilnaproxeno. Tanto el naproxeno como el 6-O-desmetilnaproxeno se metabolizan
posteriormente a sus respectivos metabolitos conjugados con acilglucurónidos. La excreción urinaria es la vía de eliminación predominante.
Aproximadamente el 95% del naproxeno se excreta en la orina; menos del 1% como fármaco inalterado, menos del 1% como 6-O-
desmetilnaproxeno y entre el 66% y el 92% como sus conjugados. Pequeñas cantidades, el 3% o menos de una dosis administrada, se excretan en
las heces. El anión naproxeno tiene una semivida plasmática de 12 a 17 horas. 32122

Isoenzimas del citocromo P450 y transportadores de fármacos afectados: CYP1A2, CYP2C8, CYP2C9

El naproxeno es un sustrato de las isoenzimas del citocromo hepático CYP1A2, CYP2C8 y CYP2C9; CYP2C9 parece ser la principal vía del
sustrato. 34493 34495

•Farmacocinética específica de la vía

Vía oral

Las diferentes formas de dosificación de naproxeno son bioequivalentes en términos de grado de absorción (AUC) y concentración máxima; sin
embargo, los productos difieren en su patrón de absorción. El naproxeno y el naproxeno sódico se absorben rápida y completamente en el tracto
gastrointestinal. El inicio del alivio del dolor puede ocurrir dentro de 1 hora en pacientes que toman naproxeno y 30 minutos en pacientes que
toman naproxeno sódico. Se ha encontrado que el efecto analgésico dura hasta 12 horas. Las concentraciones plasmáticas máximas de
naproxeno se alcanzan de 2 a 4 horas y de 1 a 2 horas después de la ingestión de naproxeno y naproxeno sódico, respectivamente. La diferencia
en las velocidades entre los 2 productos se debe a la mayor solubilidad acuosa de la sal sódica de naproxeno. El recubrimiento de polímero
entérico para naproxeno con cubierta entérica se disuelve por encima de pH 6. El naproxeno con cubierta entérica se disuelve principalmente en
el intestino delgado en lugar de en el estómago, por lo que la absorción del fármaco se retrasa hasta que se vacía el estómago. Cuando se
administró naproxeno con cubierta entérica a sujetos en ayunas, las concentraciones plasmáticas máximas se alcanzaron aproximadamente de 4
a 6 horas después de la primera dosis (rango: 2 a 12 horas). Cuando se administró naproxeno con cubierta entérica con alimentos, las
concentraciones plasmáticas máximas se alcanzaron en aproximadamente 12 horas (rango: 4 a 24 horas). La presencia de alimentos prolongó el
tiempo que los comprimidos permanecieron en el estómago, el tiempo hasta las primeras concentraciones séricas detectables de naproxeno y el
tiempo hasta las concentraciones máximas de naproxeno, pero no afectó las concentraciones máximas de naproxeno. La semivida de
eliminación del naproxeno no varía en todos los productos y varía de 12 a 17 horas. Las concentraciones en estado estacionario se alcanzan en 4
a 5 días. 32122

•Poblaciones especiales

Insuficiencia hepática

Naproxen pharmacokinetics have not been determined in patients with hepatic insufficiency. In patients with chronic alcoholic
hepatic disease and other diseases with decreased or abnormal plasma proteins (i.e., hypoalbuminemia), the total plasma
concentration of naproxen may be reduced, but the plasma concentration of unbound naproxen is increased. 32122

Renal Impairment

Naproxen pharmacokinetics have not been determined in patients with renal insufficiency. Naproxen metabolites may
accumulate in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal
impairment. 32122

Pediatrics

In pediatric patients aged 5 to 16 years with arthritis, plasma naproxen concentrations after a single naproxen suspension 5
mg/kg dose were found to be similar to those in normal adults after a 500 mg dose. The terminal half-life appears to be similar
in pediatric and adult patients. 32122

Geriatric

Although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the
elderly, although the unbound fraction is less than 1% of the total naproxen concentration. Unbound trough naproxen
concentrations in elderly subjects have been reported to range from 0.12% to 0.19% of total naproxen concentration, compared
with 0.05% to 0.075% in younger subjects. The clinical significance of this finding is unclear. 32122

Monitoring Parameters
Monitoring Parameters

CBC serum creatinine/BUN

LFTs
Classifications
Musculo-Skeletal System

Antiinflammatory Agents and Antirheumatic Agents

Antiinflammatory and Antirheumatic Agents

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Global Drug Names

Argentina

Aleve - (Bayer Consumer)

Alginoprox - (Omicron)

Algioprux - (Sidus)

Alidase - (Bernabo)

Bumaflex N - (Takeda)

Causalon Pro - (Phoenix)

Congex - (Buxton)
Debril - (Monserrat)

Dolgesic - (Lafedar)

Dolpark - (Elea)

Fabralgina - (Fabra)

Fadalivio - (Fada)

Flaxvan - (Rontag)

Flogocefal - (Lacefa)

Keldor - (GP)

Melgar - (Fada)

Monarit - (Rontag)

Mox - (Elea)

Naprofidex - (Fidex)

Naprogen - (Klonal)

Naprontag - (Rontag)

Naproxphar - (Wunderpharm)

Naprux - (Andromaco)
Neuralprona - (Bioquimico)

Sicadentol Plus - (Geminis)

Tundra - (Frasca)

Veradol - (Serch)

Vimovo - (AstraZeneca)

Xicane - (Sanofi Synthelabo)

Australia

Aleve - (Roche Consumer)

 Anaprox - (Atnahs)

Chemists Own Period Pain - (Chemists Own)

Crysanal - (Atnahs)

Femme Free - (Ascent)

Inza - (Alphapharm)

Naprogesic - (Bayer Consumer)

Naprosyn - (Atnahs)

Naxen - (Alphapharm)

Nurolasts - (Boots Healthcare)

Proxen - (Atnahs)

Synflex - (Syntex)

Vimovo - (AstraZeneca)

Austria

Aleve - (Bayer)

Miranax - (Grunenthal)

Naprobene - (Ratiopharm)

Nycopren - (Nycomed)

Proxen - (Grunenthal)

Vimovo - (AstraZeneca)

Xenopan - (Mundipharma)

Belgium

Aleve - (Bayer)

Apra-Gel - (Roche)

Apranax - (CSP)

Diparene - (Bios)
Naproflam - (Socobom)

Naprosyne - (CSP)

Nycopren - (Farmabel)

Vimovo - (AstraZeneca)

Brazil

Flamaprox - (Globo)

Flanax - (Bayer)

Naproflen - (Sandoz)

Napronax - (Neo Quimica)

Naprosyn - (Bayer)

Naprox - (Teuto)

Naxotec - (Uniao Quimica)

Vimovo - (AstraZeneca)

Canada

Aleve - (Bayer Consumer)

 Anaprox - (Roche)

Apo-Napro-Na - (Apotex)

Maxidol - (Bayer Consumer)

Naprelan - (Sunovion)

Naprosyn - (Roche)

Naxen - (Altimed)

Novo-Naprox - (Novopharm)

Nu-Naprox - (Nu-Pharm)

Rhodiaprox - (Rhodiapharm)
Roche - (Syntex)

Synflex - (Altimed)

Vimovo - (AstraZeneca)

Chile

Atac - (K2 Health & Wellness)

Deucoval - (Medipharm)

Eurogesic - (Saval)

Flanax - (Bayer)

Flogotone - (Interpharma)

Inveoxel - (Drag)

Naprogesic - (Bayer)

Reprost - (Andromaco)

Salvis - (Abbott)

Triox NF - (Andromaco)

Vimovo - (AstraZeneca)

China
An Li - (Bayer)

Ao Pu Li - (Di Ao)

Bai Tong - (Qing Yu Tang)

Bei Li - (Deyer)

Hui Ke - (Wecome)

Jia Dan - (Bei Da Gao Ke Hua Tai)

Jie Jie - (Hui Feng)

Jinkangpuli - (Conba)

Mai Er - (Yaoyou)

Na Pu Xing - (Jin Yuan)

Napton - (Bao Ling Fu Jin)

Qi Gu Ke - (Huang Long)

Shi Luo Te - (Nhwa)

Tai Ze - (Pude)

YuanQi - (Li Jie Xun)

Czech Republic

Aleve - (Bayer)

Emoxen - (PharmaSwiss)

Etrixenal - (Proenzi)

Nalgesin - (KRKA)

Naprobene - (Merckle)

Naprosyn - (KRKA)

Napsyn - (ICN)

Vimovo - (AstraZeneca)
Denmark

Alpoxen - (Alpharma)

Bonyl - (Orion)

Daprox - (Nycomed)

Eox - (Meda)

Miranax - (Roche)

Napronet - (Nettopharma)

Naprosyn - (Roche)

Nycopren - (Nycomed)

Vimovo - (AstraZeneca)

Finland

Alpoxen - (Actavis)

Eox - (Meda)

Miranax - (Roche)

Naprometin - (Roche)

Napromex - (Ratiopharm)
Naprosyn - (Roche)

Naxopren - (Mylan)

Nycopren - (Nycomed)

Pronaxen - (Orion)

Vimovo - (AstraZeneca)

France

Alevetabs - (Bayer Consumer)

Antalnox - (Pierre Fabre)

Apranax - (Roche)

Naprosyne - (Grunenthal)

Germany

Alacetan NNA - (Asconex)

Aleve - (Bayer)

Apranax - (Syntex)

Dolormin mit Naproxen - (McNeil)

 Dysmenalgit - (Krewel)

Malexin - (BASF)

Mobilat Schmerztabletten mit Naproxen - (Stada)

Napro-Dorsch - (Orion)

prodolor - (Stada)

Proxen - (Roche)

Vimovo - (AstraZeneca)

Greece

Anaprox - (Minerva (Μινερβα))

Anexopen - (Coup)

Momendol - (Angelini)

Naprosyn - (Minerva (Μινερβα))

Nopron - (Vianex (Βιανεξ))

Nycopren - (Nycomed)

Hong Kong

Aleve - (Bayer)

Apo-Napro-Na - (Hind Wing)

Genoxen - (Antigen)

Inza - (Alphapharm)

Naposin - (Hitpharm)

Naprorex - (LF)

Naprosyn - (Roche)

Napxen - (APT)

Noflam-N - (Pacific)

Point - (Gaily)
Proxen - (Medochemie)

Safrosyn S - (HealthCare PharmaScience)

Sinton - (Hitpharm)

Snofin - (LSB)

Soden - (DHA)

Soren - (HealthCare PharmaScience)

Synflex - (Roche)

Uprogesic - (Star)

Hungary

Aleve - (Bayer)

Analgesin - (KRKA)

Apranax - (PharmaSwiss)

Etrixenal - (Proenzi)

Napmel - (PannonPharma)

Naprosyn - (PharmaSwiss)
 Vimovo - (AstraZeneca)

India

Antesvel - (Martel Hammer)

Artagen - (Ranbaxy)

Easy Dayz - (Cipla)

Movibon - (Micro)

Napexar - (RPG)

Napris - (Symbiosis)

Naprosyn - (RPG)
Napryn - (Themis)

Naxen - (Elder)

Xenobid - (Rallis)

Indonesia

Naxen - (Darya-Varia)

Synflex - (Darya-Varia)

Xenifar - (Ifars)

Ireland

Genoxen - (Antigen)

Gerinap - (Gerard)

Momendol - (Angelini)

Napmel - (Clonmel)

Naprex - (Pinewood)

Naprosyn - (Atnahs)

Stirlescent - (Stirling Anglian)

Synflex - (Roche)
Vimovo - (AstraZeneca)

Israel

Aponacin - (Curex)

Naprex - (Curex)

Naproxi - (Gerard)

Narocin - (Teva)

Naxyn - (Teva)

Point - (Trima)

Vimovo - (AstraZeneca)

Italy

Akudol - (Wassermann)

Aleve - (Bayer)

Alganil - (IBIS)

Algonapril - (Crinos)

Aperdan - (ABC)
Artroxen - (Errekappa)

AS/85 - (Aesculapius)

Axer - (Wassermann)

D/N PR - (Magis)

Dropsen - (Eyelab)

Floginax - (Teofarma)

Flogogin - (Angelini)

Flogogin - (Tosi)

Floxalin - (Bioprogress)
Gibinap - (Metapharma)

Gibixen - (Metapharma)

Gynestrel - (Recordati)

Laser - (Princeps)

Leniartril - (San Carlo)

Momendol - (Angelini)

Napreben - (Merqurio)

Naprium - (Radiumfarma)

Naprius - (Aesculapius)

Naprocet - (Boniscontro & Gazzone)

Naprodol - (Upsamedica)

Naprorex - (Lampugnani)

Naprossene - (EG)

Naprosyn - (Recordati)

Natrioxen - (Benedetti)

Neo Eblimon - (Guidotti)

Nitens - (Crinos)

Numidan - (Therabel)

Piproxen - (Nuovo ISM)

Praxenol - (Biotekfarma)

Prexan - (New Research)

Primeral - (Master Pharma)

Provindol - (E-Pharma)

Proxagol - (Union Health)

Proxine - (Del Saz & Filippini)

Synalgo - (Geymonat)

Synflex - (Recordati)

Ticoflex - (Uno)

Uninapro - (Farmakopea)

Vimovo - (AstraZeneca)

Xenar - (Wassermann)
Japan

Naixan - (Mitsubishi Tanabe)

Malaysia

Apo-Napro-Na - (Apotex)

Inza - (Alphapharm)

Roxyn - (Raza)

Safrosyn S - (Pharmaniaga)

Seladin - (YSP)

Sunprox - (Sunward)
Synflex - (Roche)

Vimovo - (AstraZeneca)

Mexico

Actiquim - (Quimica y Farmacia)

Acxen - (Loren)

Alliviax - (Genomma)

Alxen - (Ofimex)

Anaflin - (Ehlinger)

Analgen - (Liomont)

Analgen Forte - (Liomont)

Anapsyl - (Novag)

Arsenal - (IQFA)

Arsenal Compuesto - (IQFA)

Artron - (Liomont)

Arxen - (Arlex)

Arxen Compositum - (Arlex)

Atiflan - (Ederka)

Bifardol - (Liferpal)

Bioxan - (Bioresearch)

Bixen - (Biomep)

Brax - (Biomep)

Bremol - (Alpharma)

Dafloxen - (Liomont)

Dafloxen-F - (Liomont)

Dartrox - (Pisa)

Decosil - (Collins)

Deflamox - (Sanfer)

Deflamox Plus - (Hormona)

Diferbest - (Best)

Divadays - (Apotex)

Dolnaxen - (Arlex)
Doloatrixen - (Zerboni)

Dolotandax - (Sandoz)

Dolxen - (Maver)

Donaprox - (Reuffer)

Drunen - (Andromaco)

Edem - (Wermar)

Fagofen - (Grisi)

Faraxen - (Randall)

Farxen - (Farcoral)
Febrax - (Rhein)

Fiverdol - (Maver)

Flanax - (Bayer Consumer)

Flavoxen - (Alpharma)

Flaxendol - (Vitae)

Flaxenol - (Raam)

Flexen - (Rayere)

Flogen - (Teva)

Fuxen - (Teva)

Genalgen - (Farmaco)

Inflanox - (Mavi)

Iqfasol - (IQFA)

Kenaprox - (Kener)

Kensedal - (Precimex)

Lixogan - (Tocogino)

Lorexen - (Loren)
Luzapren - (Alvartis)

Messelxen - (Biomep)

Movex - (Rayere)

Naflapen - (Collins)

Napoxol - (Ultra)

Naprodil - (Diba)

Naprodil Plus - (Diba)

Nasocan - (Protein)

Navixen - (Mavi)

Naxen - (Rhein)

Naxil - (Galen)

Naxopaar - (Parggon)

Nedoxal - (Quimica y Farmacia)

Neonaxil - (Probiomed)

Neorpan Plus - (Quimica y Farmacia)

 Nixal - (Columbia)

Novadex - (Novag)

Novaxen - (Novag)

Onexmol - (Best)

Pactens - (Merck)

Patxen - (Ehlinger)

Pensodil - (Loeffler)

Polet - (Wermar)

Praxedol - (Probiomed)
Profaxen - (Nafar)

Pronat - (Solfran)

Pronax-P - (Kener)

Pronaxil - (Streger)

Pronoxen - (Farcoral)

Propional - (Silanes)

Proxalin - (Degorts)

Proxalin Plus - (Degorts)

Proxem - (Hexal)

Raxenol - (Mavi)

Reucortil - (Mayo)

Salupran - (Protein)

Sertrixen - (Serral)

Sodixen - (Rayere)

Tandax - (Sandoz)

Tanizona - (Offenbach)
Taxenan - (Mavi)

Ulpafie-N - (Ultra)

Unirelaxed - (Alpharma)

Vantin - (Best)

Velsay - (Sons)

Velsay-S Compuesto - (Sons)

Vimovo - (AstraZeneca)

Viplus - (Parggon)

Xenorac's - (Farmaceutica H)

Netherlands

Aleve - (Bayer)

Femex - (Roche)

Momendol - (ACRAF)

Naprelan - (Alkermes)

Naprocoat - (Roche)
 Naprosyne - (Roche)

Naprovite - (Roche)

Naproxavi - (Disphar)

Nycopren - (Sanofi Synthelabo)

Vimovo - (AstraZeneca)

New Zealand

Naprogesic - (Bayer)

Naprosyn - (Clinect)

Naxen - (Douglas)
Noflam - (Mylan)

Sonaflam - (Multichem)

Synflex - (Roche)

Vimovo - (AstraZeneca)

Norway

Alpoxen - (Alpharma)

Ledox - (Weifa)

Napren - (Takeda)

Naprosyn - (Roche)

Proxan - (Karo)

Vimovo - (AstraZeneca)

Philippines

Alpron - (Aldril)

Aprelax - (Blue Sky)

Flacidon - (Lloyd)

Flanax - (Taisho)
Naflax - (Gold Coast)

Napoxen - (Sel-J)

Naprelan - (OEP)

Naprosyn - (Roche)

Naxen - (Interphil)

Nopen - (Ashford)

Penles - (Ashford)

Sanomed - (Vitalink)

Skelan - (Unilab)

Skelan Protect - (Amherst)

Vimovo - (AstraZeneca)

Poland

Aleve - (Bayer)

Anapran - (Polfa Pabianice)

Apo-Napro - (Apotex)
 Boloxen - (Kato)

DiFortan - (Emo-Farm)

Emochol - (Emo-Farm)

Etrixenal - (Proenzi)

Nalgesin - (KRKA)

Napritum - (Vitama)

Natrax - (Polfa Pabianice)

Naxii - (US Pharmacia)

Neoxen - (PharmaSwiss)
Tarproxen - (Polfa Tarchomin)

Vimovo - (AstraZeneca)

Portugal

Ilgesin - (KRKA)

Momendol - (Angelini)

Naprocet - (Tecnifar)

Naprosyn - (Roche)

Reuxen - (Tecnifar)

Vimovo - (AstraZeneca)

Russian Federation

Algezir - (Obolenskoe)

Motrin - (Johnson & Johnson)

Nalgesin - (KRKA)

Vimovo - (AstraZeneca)

Singapore

Aleve - (Bayer)
Anax - (Whan In)

Apo-Napro-Na - (Apotex)

Bipronyl - (Pharmachemie)

Gesiprox - (Kalbe)

Inza - (Alphapharm)

Naprosyn - (Roche)

Noflam-N - (Merck)

Nuprafen - (Beximco)

Seladin - (Yung Shin)

Soden - (DHA)

Soproxen - (Berlin Pharm)

Soren - (Daewon)

SP-Anflam - (Sunward)

Sunprox - (Sunward)

Synflex - (Roche)
 Vimovo - (AstraZeneca)

Zynal - (Korean Drug)

South Africa

Acusprain - (Apotex)

Aleve - (Bayer Consumer)

Clinosyn - (Norton)

Fibroxyn - (Garec)

Nafasol - (Aspen)

Napflam - (Aspen)
Naprel - (Brunel)

Naproscript - (Caps)

Naprosyn - (Roche)

Naxen - (Rolab)

Pranoxen - (Propan)

Proxen - (Garec)

Synflex - (Roche)

Traumox - (Medpro)

Spain

Aleve - (Bayer)

Aliviomas - (Alacan)

Alprofen - (Cusi)

Anaprox - (Roche)

Antalgin - (Roche)

Denaxpren - (Coll)

Ilagane - (Daker Farmasimes)

Lundiran - (Vir)

Madaprox - (Madariaga)

Momen - (Angelini)

Naprokes - (Inexfa)

Naprosyn - (Atnahs)

Naproval - (Reig Jofre)

Numide - (Hosbon)

Proxen - (Almirall)

Rofanten - (Belmac)

Sobronil - (Septa)

Tacron - (Farmasierra)

Vimovo - (AstraZeneca)

Sweden

Alpoxen - (Actavis)

Eox - (Antula)
 Miranax - (Syntex)

Naprelan - (Meda)

Naprocur - (Evolan)

Naprosyn - (Roche)

Pronaxen - (Orion)

Vimovo - (AstraZeneca)

Switzerland

Aleve - (Bayer)

Apranax - (Roche)
Naprolag - (Lagap)

Naprosyn - (Roche)

Nycopren - (Nycomed)

Proxen - (Grunenthal)

Servinaprox - (Servipharm)

Vimovo - (AstraZeneca)

Thailand

Annoxen - (Siam Bheasach)

Artagen - (Ranbaxy)

Buproxen - (Burapha)

Flexin - (Douglas)

Naproflex - (Central)

Naprosian - (Asian Pharm)

Naproso - (M & H)

Naprosyn - (Roche)

Napsen - (Sriprasit)
Napxen - (Berlin Pharm)

Narzen - (Shiwa)

Nasin - (Medicpharma)

Naxene - (Suphong)

Polyxen - (Central)

Prodaril-N - (Medicine Products)

Proxen - (Pharmaland)

Roxen - (Hua)

Serviproxan - (Sandoz)

Sonap - (Sriprasit)

Soproxen - (Berlin Pharm)

Synflex - (Roche)

Synogin - (Chinta)

U-Proxyn - (Unison)

Vinsen - (Chew)
Turkey

A-Nox - (Aroma)

Aleve - (Bayer)

Anaprotab - (Sanli)

Apraljin - (Deva)

Apranax - (Abdi)

Apraxin - (Abdi)

Aprodent - (Dentoral)

Aprol - (Bilim)
Apromed - (Kocak)

Aprowell - (Ali)

Armanaks - (Acon)

Atren - (Ilacsan)

Bonmin - (Aksu)

Exvile - (Tripharma)

Femidolor - (Sandoz)

Floneks - (Terra)

Inaprol - (Bilim)

Kapnax - (Sandoz)

Karoksen - (Munir)

Mednap - (Kocak)

Naponal - (Munir)

Napradol - (Actavis)

Napren - (Sandoz)

Napro-Pac - (Abdi)
Naprodev - (Deva)

Naprodex - (Ilacsan)

Naproff - (World Medicine)

Naprosyn - (Abdi)

Naprotab - (Sanli)

Nexpro - (World Medicine)

Opraks - (Toprak)

Relokap - (Yeni)

Romaksen - (Ulagay)

Rumazolidin - (Osel)

Seroksen - (SSK)

Sodinax - (Osel)

Synax - (Biofarma)

Syndol - (Husnu Arsan)

Ukraine
 Anapran - (Adamed)

Nalgesin - (KRKA)

Naproff - (Rotapharm)

Promax - (Hikma)

United Arab Emirates

Axen - (Julphar)

United Kingdom

Arthrosin - (Ashbourne)

Arthroxen - (CP Pharmaceuticals)

Condrotec - (Searle)

Feminax Ultra - (Bayer)

Laraflex - (Lagap)

Napratec - (Pharmacia)

Naprosyn - (Roche)

Nycopren - (Ardern)

Period Pain Relief - (Boots)

Pranoxen Continus - (Napp)

Prosaid - (BHR)

Rheuflex - (Goldcrest)

Rimoxyn - (Rima)

Stirlescent - (Stirling Anglian)

Syndol Period Pain Relief - (Boots)

Synflex - (Roche)

Timpron - (Berk)

Valrox - (Shire)
Vimovo - (AstraZeneca)

Venezuela

Apranax - (Roche)

Nadolex - (Farma)

Norane - (Arex)

Pronoflex - (GS)

Synaprosyn - (Roche)

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