Methylphenidate: Pediatric drug information http://uptodate.sescam.csinet.es/contents/methylphenidate-pediatri...

Official reprint from UpToDate®

www.uptodate.com ©2015 UpToDate®

Methylphenidate: Pediatric drug information

Copyright 1978-2015 Lexicomp, Inc. All rights reserved.

(For additional information see "Methylphenidate: Drug information" and see "Methylphenidate: Patient drug
information")

For abbreviations and symbols that may be used in Lexicomp (show table)

Special Alerts

FDA Concerns About Therapeutic Equivalence of Two Generic Versions of Concerta November 2014

The FDA has changed the therapeutic equivalence rating for two approved generic versions of Janssen’s
Concerta (methylphenidate hydrochloride) extended-release tablets from AB to BX, based on concerns that
the products may not be therapeutically equivalent to the brand name drug. FDA laboratory tests of the two
generics, manufactured by Mallinckrodt Pharmaceuticals and Kudco, have raised concerns that the products
may not produce the same therapeutic benefits for some patients as Concerta.

The products are still approved and can be prescribed, but are no longer recommended as automatically
substitutable at the pharmacy, or by a pharmacist, for Concerta. The FDA has not identified any serious
safety concerns with these two generic products. Patients should not make changes to their treatment
except in consultation with their health care professional.

Patients or health care providers with concerns about lack of desired effect during the dosing period should
contact the prescribing health care provider to discuss whether a different drug product would be more
appropriate.

For more information see http://www.fda.gov/Drugs/DrugSafety/ucm422568.htm.

ALERT: U.S. Boxed Warning

Abuse and dependence:

Methylphenidate has a high potential for abuse and dependence. Give methylphenidate cautiously to
patients with a history of drug dependence or alcoholism.

Long-term abusive use can lead to marked tolerance and psychological dependence with varying degrees of
abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful
supervision is required during withdrawal from abusive use because severe depression may occur.
Withdrawal following long-term therapeutic use may unmask symptoms of the underlying disorder that
may require follow-up. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and
dependence while on therapy.

Brand Names: U.S. Concerta; Daytrana; Metadate CD; Metadate ER; Methylin; Quillivant XR; Ritalin;
Ritalin LA; Ritalin SR [DSC]

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Brand Names: Canada Apo-Methylphenidate; Apo-Methylphenidate SR; Biphentin; Concerta;

PHL-Methylphenidate; PMS-Methylphenidate; ratio-Methylphenidate; Ritalin; Ritalin SR; Sandoz-
Methylphenidate SR; Teva-Methylphenidate ER-C

Therapeutic Category Central Nervous System Stimulant

Dosing: Usual
(For additional information see "Methylphenidate: Drug information")

Note: Discontinue medication if no improvement is seen after appropriate dosage adjustment over a
1-month period of time:

Children and Adolescents:

Attention-deficit/hyperactivity disorder:

Oral:

Immediate release products (eg, Methylin®, Ritalin®):

Children 3-5 years, moderate to severe dysfunction: Limited data available; AAP considers
first-line agent in this patient population if pharmacological treatment deemed
necessary (AAP, 2011): Initial: 1.25 mg twice daily; titrate to effect at weekly intervals;
usual reported daily range: 3.75-30 mg/day divided into two or three daily doses
(Ghuman, 2008; Greenhill, 2006). In the largest trial, a multicenter, randomized,
placebo-controlled, crossover study of 165 preschool children (age range: 3-5.5
years), statistically and clinically significant improvements in ADHD scores were
reported with doses of 2.5 mg, 5 mg, and 7.5 mg 3 times daily; in some patients [n=7
(4%)], dose titration to 10 mg 3 times daily was necessary; the mean effective total
daily dose: 14.2 ± 8.1 mg/day. Although ADHD scores were statistically and clinically
improved with methylphenidate use, the effect size was smaller with this younger
patient population than that seen in school-age children (Greenhill, 2006).

Children ≥6 years and Adolescents: Initial: 0.3 mg/kg/dose or 2.5-5 mg/dose given before
breakfast and lunch; increase by 0.1 mg/kg/dose or by 5-10 mg/day at weekly
intervals; usual dose: 0.3-1 mg/kg/day or 20-30 mg/day in 2-3 divided doses;
maximum daily dose dependent upon patient weight: 2 mg/kg/day or if patient weight
≤50 kg: 60 mg/day; in patients >50 kg: 100 mg/day (Dopheide, 2009, Pliszka, 2007);
some patients may require 3 doses/day (ie, additional dose at 4 PM)

Extended release, sustained release and long acting products:

Metadate® ER, Ritalin-SR®: Children ≥6 years and Adolescents: Sustained release and
extended release tablets (duration of action ~8 hours) may be given in place of
regular tablets, once the daily dose is titrated using the immediate release products
and the titrated 8-hour dosage corresponds to sustained/extended release tablet size;
Ritalin SR® may be administered once or twice daily (AAP, 2011). Maximum daily
dose is dependent upon patient weight: ≤50 kg: 60 mg/day; >50 kg: 100 mg/day
(Dopheide, 2009; Pliszka, 2007)

Concerta®: Children ≥6 years and Adolescents:

Methylphenidate-naive patients: Initial: 18 mg once daily

Patients currently using immediate release methylphenidate: Initial dose: Dosing

based on current regimen and clinical judgment; suggested dosing listed below:

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Switching from methylphenidate immediate release 5 mg 2-3 times daily:

Concerta® 18 mg once daily

Switching from methylphenidate immediate release 10 mg 2-3 times daily:

Concerta® 36 mg once daily

Switching from methylphenidate immediate release 15 mg 2-3 times daily:

Concerta® 54 mg once daily

Switching from methylphenidate immediate release 20 mg 2-3 times daily:

Concerta® 72 mg once daily

Dosage adjustment: May increase by Concerta® 18 mg/day increments at weekly

intervals. Note: A dosage strength of 27 mg is available for situations in which a
dosage between 18-36 mg is desired.

Maximum daily dose:

Children 6-12 years: 54 mg/day; for patients >50 kg, higher maximum daily doses
may be considered (108 mg/day)

Adolescents:

≤50 kg: 72 mg/day; not to exceed ~2 mg/kg/day

>50 kg:108 mg/day (Dopheide, 2009; Pliszka, 2007)

Metadate CD®: Children ≥6 years and Adolescents: Initial: 20 mg once daily; may
increase by 10-20 mg/day increments at weekly intervals; maximum daily dose
dependent upon patient weight: ≤50 kg: 60 mg/day; >50 kg: 100 mg/day (Dopheide,
2009; Pliszka, 2007)

Quillivant™ XR: Children 6-12 years: Initial: 20 mg once daily; may increase by 10-20
mg/day increments at weekly intervals; maximum daily dose: 60 mg/day

Ritalin LA®: Children ≥6 years and Adolescents:

Methylphenidate-naive patients: Initial: 20 mg once daily; may increase by 10 mg/day

increments at weekly intervals; maximum daily dose dependent upon patient
weight: ≤50 kg: 60 mg/day; >50 kg: 100 mg/day (Dopheide, 2009; Pliszka, 2007).
Note: If a lower initial dose is desired, patients may begin with Ritalin LA® 10 mg
once daily. Alternatively, patients may begin therapy with an immediate release
product, and switch to Ritalin LA® once immediate release dosage is titrated to 5
mg twice daily (see below)

Patients currently receiving immediate release methylphenidate: Initial dose: Dosing

based on current regimen and clinical judgment; use equivalent total daily dose
administered once daily.

Patients currently receiving methylphenidate sustained release (SR): The same total
daily dose of Ritalin LA® should be used.

Dosage adjustment: May increase Ritalin LA®: by 10 mg/day increments at weekly

intervals

Maximum daily dose: Dependent upon patient weight: ≤50 kg: 60 mg/day; >50 kg:
100 mg/day (Dopheide, 2009; Pliszka, 2007)

Topical: Transdermal patch (Daytrana®): Children and Adolescents 6-17 years: Initial: 10 mg (12.5
cm2) patch once daily; apply to hip 2 hours before effect is needed and remove 9 hours after

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application; titrate dose based on response and tolerability; may increase to next transdermal
patch dosage size no more frequently than every week. Patch may be removed before 9 hours
if a shorter duration of action is required or if late day adverse effects appear. Plasma
concentrations usually start to decline when the patch is removed but drug absorption may
continue for several hours after patch removal. Note: The manufacturer’s labeling
recommends patients converting from another formulation of methylphenidate to the
transdermal patch should be initiated at 10 mg regardless of their previous dose and titrated as
needed due to the differences in bioavailability of the transdermal formulation. However, some
clinicians have supported higher starting patch doses for patients converting from oral
methylphenidate doses of >20 mg/day; for example, the 15 mg (18.75 cm2) patch has been
investigated to have the same effect as 22.5 mg daily of the immediate release preparation, 27
mg daily of the osmotic release preparation (Concerta®), or 20 mg daily of the encapsulated
bead preparation (Metadate CD®) (Arnold, 2007).

Narcolepsy: Children ≥6 years and Adolescents: Oral:

Immediate release tablets and oral solution (Methylin®, Ritalin®): Initial: 5 mg twice daily given
before breakfast and lunch; increase by 5-10 increments mg/day at weekly intervals; 2-3 times
per day; maximum daily dose: 60 mg/day (in 2-3 divided doses)

Extended/sustained release tablets (Metadate® ER, Ritalin-SR®): May be given in place of

immediate release products (duration of action: ~8 hours), once the immediate release
formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or
extended release tablet size; maximum daily dose: 60 mg/day

Adults:

Attention-deficit/hyperactivity disorder: Oral:

Immediate release (IR) products (tablets, chewable tablets, and solution): Initial: 5 mg twice daily,
before breakfast and lunch; increase by 5-10 mg daily at weekly intervals; maximum dose: 60
mg daily (in 2-3 divided doses)

Extended release (ER), sustained release (SR) products (capsules, tablets, and oral suspension):

Concerta®: Adults <65 years:

Patients not currently taking methylphenidate: Initial dose: 18-36 mg once every morning

Patients currently taking methylphenidate: Note: Initial dose: Dosing based on current
regimen and clinical judgment; suggested dosing listed below:

Switching from methylphenidate 5 mg 2-3 times daily: 18 mg once every morning

Switching from methylphenidate 10 mg 2-3 times daily: 36 mg once every morning

Switching from methylphenidate 15 mg 2-3 times daily: 54 mg once every morning

Switching from methylphenidate 20 mg 2-3 times daily: 72 mg once every morning

Dose adjustment: May increase dose in increments of 18 mg; dose may be adjusted at
weekly intervals. A dosage strength of 27 mg is available for situations in which a
dosage between 18-36 mg is desired; maximum dose: 72 mg/day

Metadate® ER, Ritalin-SR®: May be given in place of immediate release products, once the
daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or extended
release tablet size; maximum: 60 mg/day

Metadate CD®, Quillivant™ XR : Initial: 20 mg once daily; may be adjusted in 10-20 mg

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increments at weekly intervals; maximum: 60 mg/day

Ritalin LA®: Initial: 20 mg once daily (l0 mg once daily may be considered for some patients);
may be adjusted in 10 mg increments at weekly intervals; maximum: 60 mg/day

Conversion from immediate release or sustained release methylphenidate formulation to Ritalin

LA®: Use equivalent total daily dose administered once daily.

Narcolepsy: Oral:

Immediate release tablets and solution (Methylin®, Ritalin®): Initial: 5 mg twice daily before
breakfast and lunch; increase by 5-10 mg daily at weekly intervals; 10 mg 2-3 times per day;
maximum daily dose: 60 mg/day (in 2-3 divided doses).

Extended/sustained release tablets (Metadate® ER, Ritalin-SR®): May be given in place of

immediate release products (duration of action: ~8 hours), once the immediate release
formulation daily dose is titrated and the titrated 8-hour dosage corresponds to sustained or
extended release tablet size; maximum: 60 mg/day

Dosing adjustment for renal impairment:

Oral: No dosage adjustment provided in manufacturer’s labeling (has not been studied); undergoes
extensive metabolism to a renally eliminated metabolite with little or no pharmacologic activity.

Transdermal: No dosage adjustment provided in manufacturer’s labeling (has not been studied).

Dosing adjustment for hepatic impairment: There are no dosage adjustments provided in manufacturer's
labeling (has not been studied).

Dosage Forms: U.S. Excipient information presented when available (limited, particularly for
generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release, Oral, as hydrochloride:

Metadate CD: 10 mg, 20 mg, 30 mg [contains fd&c blue #2 (indigotine)]

Metadate CD: 40 mg

Metadate CD: 50 mg [contains fd&c blue #2 (indigotine)]

Metadate CD: 60 mg

Generic: 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Ritalin LA: 10 mg, 20 mg, 30 mg, 40 mg

Generic: 20 mg, 30 mg, 40 mg

Patch, Transdermal:

Daytrana: 10 mg/9 hr (30 ea); 15 mg/9 hr (30 ea); 20 mg/9 hr (30 ea); 30 mg/9 hr (30 ea)

Solution, Oral, as hydrochloride:

Methylin: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL) [contains polyethylene glycol]

Generic: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL)

Suspension Reconstituted, Oral, as hydrochloride:

Quillivant XR: 25 mg/5 mL (60 mL, 120 mL, 150 mL, 180 mL) [contains sodium benzoate; banana flavor]

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Tablet, Oral, as hydrochloride:

Ritalin: 5 mg

Ritalin: 10 mg, 20 mg [scored]

Generic: 5 mg, 10 mg, 20 mg

Tablet Chewable, Oral, as hydrochloride:

Methylin: 2.5 mg, 5 mg [contains aspartame; grape flavor]

Methylin: 10 mg [scored; contains aspartame; grape flavor]

Tablet Extended Release, Oral, as hydrochloride:

Concerta: 18 mg, 27 mg, 36 mg, 54 mg

Metadate ER: 20 mg [DSC]

Metadate ER: 20 mg [additive free, color free]

Ritalin SR: 20 mg [DSC]

Generic: 10 mg, 18 mg, 20 mg, 27 mg, 36 mg, 54 mg

Generic Equivalent Available: U.S. May be product dependent

Controlled Substance C-II

Medication Guide and/or Vaccine Information Statement (VIS) An FDA-approved

patient medication guide, which is available with the product information and as follows, must be dispensed
with this medication:
Concerta: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088575.pdf

Daytrana: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088581.pdf

Metadate CD: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088635.pdf

Methylin chewable tablet: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088639.pdf

Methylin immediate release oral solution: http://www.fda.gov/downloads/Drugs/DrugSafety

/ucm088640.pdf

Quillivant XR extended release oral suspension: http://www.fda.gov/downloads/Drugs/DrugSafety

/UCM322209.pdf

Ritalin: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089090.pdf

Ritalin LA: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089092.pdf

Ritalin-SR: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089095.pdf

Administration
Oral: To avoid insomnia, last daily dose should be administered several hours before retiring.

Immediate release formulations:

Tablet (Ritalin®), oral solution (Methylin®): Administer on an empty stomach ~30-45 minutes before
meals. Ensure last daily dose is administered before 6 PM if difficulty sleeping occurs.

Chewable tablet (Methylin®): Administer on an empty stomach ~30-45 minutes before meals with at

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least 8 ounces of water or other fluid; choking may occur if not enough fluids are taken. Ensure
last daily dose is administered before 6 PM if difficulty sleeping occurs.

Extended/sustained release formulations:

Tablets:

Metadate ER®: May be taken with or without food. Swallow whole; do not crush, chew, or
break tablets.

Ritalin SR®: Administer 30-45 minutes before a meal. Swallow whole; do not crush, chew, or
break tablets.

Concerta®: May be administered without regard to food, but must be taken with water, milk, or
juice; administer dose once daily in the morning; do not crush, chew, or divide tablets

Capsules:

Metadate CD®: Administer dose once daily in the morning, before breakfast, with water, milk,
or juice; capsule may be swallowed whole or opened and contents sprinkled on a small
amount (one tablespoonful) of applesauce; immediately consume drug/applesauce
mixture; do not store for future use; swallow applesauce without chewing; do not crush or
chew capsule contents; drink fluids after consuming drug/applesauce mixture to ensure
complete swallowing of beads; do not crush, chew, or divide capsules or its contents

Ritalin LA®: Administer dose once daily in the morning; may be administered with or without
food (but some food may delay absorption); capsule may be swallowed whole or may be
opened and contents sprinkled on a small amount (one spoonful) of applesauce. Note:
Applesauce should not be warm; immediately consume drug/applesauce mixture; do not
store for future use; do not crush, chew, or divide capsule or its contents.

Powder for oral suspension (Quillivant™ XR): Administer in the morning with or without food. Shake
bottle ≥10 seconds prior to administration. Use the oral dosing dispenser provided; wash after
each use.

Topical: Transdermal (Daytrana®): Apply patch immediately after opening pouch and removing protective
liner; do not use patch if pouch seal is broken; do not cut patch; do not use patches that are cut or
damaged. If difficulty is experienced when separating the patch from the liner or if any medication (sticky
substance) remains on the liner after separation, discard that patch and apply a new patch. Apply to
clean, dry, healthy skin on the hip; do not apply to oily, damaged, or irritated skin; do not apply to the
waistline; do not premedicate the patch site with hydrocortisone or other solutions, creams, ointments,
or emollients. Apply at the same time each day, 2 hours before effect is needed. Alternate site of
application daily (ie, use alternate hip). Press patch firmly for 30 seconds to ensure proper adherence.
Remove patch 9 hours after application. Patch may be removed earlier if a shorter duration of action is
required or if late day adverse effects occur.

Avoid exposure of application site to external heat source (eg, hair dryers, electric blankets, heating
pads, heated water beds), which may significantly increase the rate and amount of drug absorbed.
Exposure of patch to water during swimming, bathing, or showering may affect patch adherence.
Do not reapply patch with dressings, tape, or other adhesives. If patch should become dislodged,
may replace with new patch (to different site) but total wear time should not exceed 9 hours.

During removal, peel off patch slowly. If needed, patch removal may be helped by applying an oil-based
product (ie, mineral oil, olive oil, or petroleum jelly) to the patch edges, gently working it underneath
the patch edges. If a patch is not able to be removed, contact a physician or pharmacist.
Nonmedical adhesive removers and acetone-based products, such as nail polish remover, should
not be used to remove patches or adhesive. If adhesive residue remains on child’s skin after patch

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removal, use an oil-based product and gently rub area to remove adhesive. Avoid touching the
sticky side of the patch. Wash hands with soap and water after handling.

Dispose of used patch by folding adhesive side onto itself, and discard in toilet or appropriate lidded
container; discard unused patches that are no longer needed in the same manner; protective pouch
and liner should be discarded in an appropriate lidded container. Note: Used patches contain
residual drug; keep all transdermal patches out of the reach of children.

Stability
Oral:

Immediate release formulations:

Chewable tablet: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.

Oral solution: Chewable: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.

Tablet: (Ritalin®): Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F);
protect from light.

Extended and sustained release formulations:

Capsule (Metadate CD®, Ritalin LA®): Store at 25°C (77°F); excursions permitted to 15°C to 30°C
(59°F to 86°F).

Tablet:

Concerta®: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect
from humidity.

Metadate® ER: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C
(59°F to 86°F); protect from moisture.

Powder for oral suspension (Quillivant™ XR): Store at 25°C (77°F), excursions permitted to 15°C to
30°C (59°F to 86°F) before and after reconstitution. Once reconstituted, bottle must be used
within 4 months; dispense in original container.

Transdermal system (Daytrana®): Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to
86°F). Keep patches stored in protective pouch. Once sealed tray or outer pouch is opened, use
patches within 2 months; once an individual patch has been removed from the pouch and the protective
liner removed, use immediately. Do not refrigerate or freeze.

Use
Oral:

Concerta®: Treatment of attention-deficit/hyperactivity disorder (ADHD) (FDA approved in ages 6-65

years)

Ritalin LA®, Quillivant™ XR: Treatment of ADHD (FDA approved in ages 6-12 years)

Metadate CD®: Treatment of ADHD (FDA approved in ages 6-15 years)

Metadate® ER, Methylin®, Ritalin®, Ritalin SR®: Treatment of ADHD, treatment of narcolepsy (All
indications: FDA approved in ages ≥6 years and adults)

Topical Patch: Daytrana®: Treatment of ADHD (FDA approved in ages 6-17 years)

Medication Safety Issues

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Sound-alike/look-alike issues:

Metadate CD may be confused with Metadate ER

Metadate ER may be confused with methadone

Methylphenidate may be confused with methadone

Ritalin may be confused with Rifadin, ritodrine

Ritalin LA may be confused with Ritalin-SR

Adverse Reactions
All dosage forms:

Cardiovascular: Angina pectoris, cardiac arrhythmia, cerebrovascular accident, cerebrovascular occlusion,

decreased pulse, heart murmur, hypertension, hypotension, increased pulse, myocardial infarction,
necrotizing angiitis, palpitations, Raynaud’s phenomenon, tachycardia, vasculitis

Central nervous system: Aggressive behavior, agitation, anxiety, cerebral arteritis, cerebral hemorrhage,
confusion, depression, dizziness (more common in adults), drowsiness, emotional lability (more
common in children), fatigue, Gilles de la Tourette's syndrome (rare), headache (more common in
adults), hypertonia, hypervigilance, irritability, insomnia, lethargy, nervousness, neuroleptic malignant
syndrome (NMS) (rare), outbursts of anger, paresthesia, restlessness, tension, toxic psychosis, vertigo,
vocal tics (children)

Dermatologic: Alopecia, erythema multiforme, excoriation (children), exfoliative dermatitis, hyperhidrosis,

skin rash (children), urticaria

Endocrine & metabolic: Decreased libido, growth suppression, weight loss

Gastrointestinal: Abdominal pain (children & adolescents), anorexia (more common in children &
adolescents), bruxism, constipation, decreased appetite (more common in adults), diarrhea, dyspepsia,
motion sickness (children), nausea, vomiting, xerostomia

Genitourinary: Dysmenorrhea, erectile dysfunction

Hematologic & oncologic: Anemia, immune thrombocytopenia, leukopenia, pancytopenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests, hepatic coma, increased serum bilirubin, increased serum
transaminases

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Arthralgia, dyskinesia, tremor

Ophthalmic: Accommodation disturbance, blurred vision, dry eye syndrome, eye pain (children), mydriasis

Respiratory: Dyspnea, increased cough, pharyngitis, pharyngolaryngeal pain, rhinitis, sinusitis, upper
respiratory tract infection

Miscellaneous: Accidental injury, fever (children & adolescents)

Rare but important or life-threatening: Bradycardia, disorientation, extrasystoles, hallucination, increased

serum alkaline phosphatase, mania, migraine, obsessive-compulsive disorder, peripheral vascular
insufficiency, priapism, seizure, supraventricular tachycardia, ventricular premature contractions

Transdermal system:

Central nervous system: Headache, insomnia, irritability

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Gastrointestinal: Decreased appetite, nausea

Infection: Viral infection

Cardiovascular: Tachycardia

Central nervous system: Dizziness (adolescents), emotional lability, vocal tic

Endocrine & metabolic: Weight loss

Gastrointestinal: Abdominal pain, anorexia, vomiting

Local: Application site reaction

Respiratory: Nasal congestion, nasopharyngitis

Rare but important or life-threatening: Allergic contact dermatitis, allergic contact sensitivity,
anaphylaxis, angioedema, hallucination, seizure

Contraindications
U.S. labeling: Hypersensitivity to methylphenidate or any component of the formulation; marked anxiety,
tension, and agitation; glaucoma; use during or within 14 days following MAO inhibitor therapy; family
history or diagnosis of Tourette's syndrome or tics

Additional contraindications: Metadate CD and Metadate ER: Severe hypertension, heart failure,
arrhythmia, hyperthyroidism, recent MI or angina; concomitant use of halogenated anesthetics

Canadian labeling: Hypersensitivity to methylphenidate or any component of the formulation; marked anxiety,
tension, and agitation; glaucoma; use during or within 14 days following MAO inhibitor therapy; family
history or diagnosis of Tourette's syndrome or tics, thyrotoxicosis, advanced arteriosclerosis,
symptomatic cardiovascular disease, or moderate-to-severe hypertension

Additional contraindications: Ritalin and Ritalin SR: Pheochromocytoma

Precautions Use with caution in patients with heart failure, recent MI, hyperthyroidism, seizures, acute
stress reactions, emotional instability, or history of substance abuse. Hematological monitoring is advised
with long term use. Rare cases of neuroleptic malignant syndrome have been reported; usually in patients
receiving concurrent mediations associated with the syndrome; one case reported with concurrent first dose
of venlafaxine.

Stimulants are associated with peripheral vasculopathy, including Raynaud's phenomenon; signs/symptoms
are usually mild and intermittent and generally improve with dose reduction or discontinuation. Digital
ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during
therapy and seek further evaluation (eg, rheumatology) if necessary.

Use with caution in preschool-age children; clinical trials have shown children 3-5 years of age are more
sensitive to methylphenidate adverse effects resulting in a greater discontinuation of therapy compared to
school-age children (discontinuation rate from trials: 11% vs <1 %) (Wigal, 2006). The moderate to severe
adverse effect profiles in children are age-related; in preschool children, the most commonly reported
adverse effects were crabbiness/irritability, emotional outbursts, difficulty falling asleep, repetitive
behavior/thoughts, and decreased appetite; in school-age children, they were decreased appetite, delay of
sleep onset, headache, and stomach ache (Wigal, 2006).

Chewable tablets contain aspartame which is metabolized to phenylalanine and must be avoided (or used

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with caution) in patients with phenylketonuria. Chewable tablets must be taken with adequate amount of
liquid, otherwise tablet may swell and block the throat or esophagus and cause choking; do not use
chewable tablets in patients who have difficulty swallowing; instruct patients to seek immediate medical
attention if chest pain, vomiting, difficulty in breathing or swallowing occur after taking chewable tablet.

Metadate CD® contains sucrose; avoid use in hereditary problems of fructose intolerance, sucrase-
isomaltose insufficiency, and glucose-galactose malabsorption. Metadate® ER contains lactose; avoid in
hereditary problems of galactose intolerance, glucose-galactose malabsorption, and the Lapp lactase
deficiency. Concomitant use of Metadate® CD or Metadate® ER with halogenated anesthetics is
contraindicated; use may cause sudden elevations in blood pressure; if surgery is planned, do not administer
Metadate® CD or Metadate® ER on day of surgery.

Warnings Serious cardiovascular events including sudden death may occur in patients with pre-existing
structural cardiac abnormalities or other serious heart problems. Sudden death has been reported in children
and adolescents; sudden death, stroke, and MI have been reported in adults. Avoid the use of CNS
stimulants in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart
rhythm abnormalities, coronary artery disease, or other serious cardiac problems that could place patients at
an increased risk to the sympathomimetic effects of CNS stimulants. Patients should be carefully evaluated
for cardiac disease prior to initiation of therapy. If symptoms of cardiovascular disease, including chest pain,
dyspnea, or fainting are exhibited, immediate medical care should be sought. Note: The American Heart
Association recommends that all children diagnosed with ADHD who may be candidates for medication,
such as methylphenidate, should have a thorough cardiovascular assessment prior to initiation of therapy.
This assessment should include a combination of medical history, family history, and physical examination
focusing on cardiovascular disease risk factors. An ECG is not mandatory but should be considered. Note:
In a recent retrospective study on the possible association between stimulant medication use and sudden
death in children, 564 previously healthy children who died suddenly in motor vehicle accidents were
compared to a group of 564 previously healthy children who died suddenly. Two of the 564 (0.4%) children in
motor vehicle accidents were taking stimulant medications compared to 10 of 564 (1.8%) children who died
suddenly. While the authors of this study conclude there may be an association between stimulant use and
sudden death in children, there were a number of limitations to the study and the FDA cannot conclude this
information impacts the overall risk:benefit profile of these medications (Gould, 2009). Note: In a large
retrospective cohort study involving 1,200,438 children and young adults (age: 2-24 years), none of the
currently available stimulant medications or atomoxetine were shown to increase the risk of serious
cardiovascular events (ie, acute MI, sudden cardiac death, or stroke) in current (adjusted hazard ratio: 0.75;
95% CI: 0.31-1.85) or former (adjusted hazard ratio: 1.03; 95% CI: 0.57-1.89) users compared to nonusers
(Cooper, 2011). It should be noted that due to the upper limit of the 95% CI, the study could not rule out a
doubling of the risk, albeit low. Note: ECG abnormalities and 4 cases of sudden cardiac death have been
reported in children receiving clonidine with methylphenidate; reduce dose of methylphenidate by 40% when
used concurrently with clonidine; consider ECG monitoring.

Stimulant medications may increase blood pressure (average increase 2-4 mm Hg) and heart rate (average
increase 3-6 bpm); some patients may experience greater increases; use stimulant medications with caution
in patients with hypertension and other cardiovascular conditions that may be exacerbated by increases in
blood pressure or heart rate. Metadate CD® and Metadate ER® use is contraindicated in patients with
severe hypertension.

Psychiatric adverse events may occur. Stimulants may exacerbate symptoms of behavior disturbance and
thought disorder in patients with pre-existing psychosis. New-onset psychosis or mania may occur with
stimulant use in patients without a prior history of psychotic illness or mania, even at standard doses. May
induce mixed/manic episode in patients with bipolar disorder; patients should be screened for bipolar

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disorder prior to treatment; consider discontinuation if such symptoms (eg, delusional thinking,
hallucinations, or mania) occur. May be associated with aggressive behavior or hostility (causal relationship
not established); monitor for development or worsening of these behaviors).

Potential for drug dependency exists [U.S. Boxed Warning]; prolonged administration may lead to drug
dependence; abrupt discontinuation following high doses or for prolonged periods may result in symptoms of
withdrawal; avoid abrupt discontinuation in patients who have received methylphenidate for prolonged
periods. Do not use for severe depression or normal fatigue states. CNS stimulants possess a high potential
for abuse [U.S. Boxed Warning]; assess risk of abuse prior to initiating therapy and continue to monitor for
signs of abuse throughout therapy; misuse may cause sudden death and serious cardiovascular adverse
events; use with caution in patients with history of ethanol or drug abuse.

Prolonged and painful erections (priapism), sometimes requiring surgical intervention, have been reported
with methylphenidate use in pediatric and adult patients. Priapism has been reported to develop after some
time on the drug, often subsequent to an increase in dose and also during a period of drug withdrawal (drug
holidays or discontinuation). Patients who develop abnormally sustained or frequent and painful erections
should seek immediate medical attention.

Long-term effects in pediatric patients have not been determined. Use of stimulants in children has been
associated with growth suppression (monitor growth; treatment interruption may be needed). Appetite
suppression may occur; monitor weight during therapy, particularly in children. Stimulants may lower seizure
threshold leading to new onset or breakthrough seizure activity (use with caution in patients with a history of
seizure disorder). Visual disturbances (difficulty in accommodation and blurred vision) have been reported.

A potential for GI obstruction exists with Concerta® (tablet is nondeformable); do not ordinarily use in
patients with severe GI narrowing (eg, esophageal motility disorders, small bowel inflammatory disease,
short gut syndrome, history of cystic fibrosis, peritonitis, chronic intestinal pseudo-obstruction, or Meckel's
diverticulum).

Transdermal system (Daytrana®) may cause allergic contact sensitization, characterized by intense local
reactions (edema, vesicles, papules) that may spread beyond the patch site; remove patch and monitor
application site if reaction occurs; seek further evaluation if erythema, edema, and/or papules do not
significantly decrease or resolve within 24 hours of patch removal. Allergic sensitization may subsequently
manifest systemically when methylphenidate is administered orally or via other routes; systemic sensitization
reactions may include dermatitis, generalized skin eruptions, headache, fever, vomiting, diarrhea, arthralgia,
or malaise; initiate oral methylphenidate under close medical supervision in patients who have experienced a
contact sensitization to the transdermal system; some of these patients may not be able to take
methylphenidate in any dosage form. Do not expose transdermal application site to direct external heat
sources (eg, electric blankets, heating pads, heated water beds), a >2-fold increase in drug release may
occur. Powder for oral suspension (Quillivant™ XR) contains benzoic acid; benzoic acid (benzoate) is a
metabolite of benzyl alcohol; which may cause allergic reactions in susceptible individuals.

Metabolism/Transport Effects Inhibits CYP2D6 (weak)

Drug Interactions

(For additional information: Launch Lexi-Interact™ Drug Interactions Program)

Alcohol (Ethyl): May enhance the adverse/toxic effect of Methylphenidate. Alcohol (Ethyl) may increase the
serum concentration of Methylphenidate. Risk X: Avoid combination

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Antacids: May increase the absorption of Methylphenidate. Specifically, antacids may interfere with the
normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both
increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Antihypertensives: Methylphenidate may diminish the antihypertensive effect of Antihypertensives. Risk C:

Monitor therapy

Anti-Parkinson's Agents (Dopamine Agonist): Methylphenidate may enhance the adverse/toxic effect of
Anti-Parkinson's Agents (Dopamine Agonist). Risk C: Monitor therapy

Antipsychotic Agents: May enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may
enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole.
Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments
may or may not be required based on concomitant therapy and/or indication. Consult full interaction
monograph for specific recommendations. Risk C: Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the
tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions:

Cannabidiol. Risk C: Monitor therapy

CloNIDine: Methylphenidate may enhance the adverse/toxic effect of CloNIDine. Risk C: Monitor therapy

Fosphenytoin: Methylphenidate may increase the serum concentration of Fosphenytoin. Risk C: Monitor
therapy

H2-Antagonists: May increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere
with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could
result in both increased absorption (early) and decreased delayed absorption. Risk C: Monitor therapy

Inhalational Anesthetics: Methylphenidate may enhance the hypertensive effect of Inhalational Anesthetics.
Risk X: Avoid combination

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X:
Avoid combination

Ioflupane I 123: Methylphenidate may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor
therapy

MAO Inhibitors: May enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination

PHENobarbital: Methylphenidate may increase the serum concentration of PHENobarbital. Risk C: Monitor
therapy

Phenytoin: Methylphenidate may increase the serum concentration of Phenytoin. Risk C: Monitor therapy

Primidone: Methylphenidate may increase serum concentrations of the active metabolite(s) of Primidone.
Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the
serum concentration of Primidone. Risk C: Monitor therapy

Proton Pump Inhibitors: May increase the absorption of Methylphenidate. Specifically, proton pump inhibitors
may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand),
which could result in both increased absorption (early) and decreased delayed absorption. Risk C:
Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor
therapy

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Tricyclic Antidepressants: Methylphenidate may enhance the adverse/toxic effect of Tricyclic

Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants.
Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Methylphenidate may increase the serum concentration of Vitamin K
Antagonists. Risk C: Monitor therapy

Food Interactions
Ethanol: Alcohol consumption increases the rate of methylphenidate release from Metadate CD and Ritalin
LA (extended-release capsules), but not from Concerta (extended-release tablet); an in vitro study
involving Metadate CD and Ritalin LA showed that an alcohol concentration of 40% resulted in 84% and
98% of the methylphenidate being released in the first hour, respectively. Management: Avoid
consuming alcohol during therapy.

Food: Food may increase oral absorption of immediate release tablet/solution and chewable tablet.
Management: Administer 30-45 minutes before meals.

Pregnancy Risk Factor C (show table)

Pregnancy Implications Adverse events were observed in animal reproduction studies. Information
related to the use of methylphenidate in pregnant women with attention-deficit/hyperactivity disorder (Bolea-
Akmanac, 2013; Dideriksen, 2013) or narcolepsy (Maurovich-Horvat, 2013; Thorpy, 2013) is limited.

Monitoring Parameters Evaluate patients for cardiac disease prior to initiation of therapy with
thorough medical history, family history, and physical exam; consider ECG; perform ECG and
echocardiogram if findings suggest cardiac disease; promptly conduct cardiac evaluation in patients who
develop chest pain, unexplained syncope, or any other symptom of cardiac disease during treatment.
Monitor CBC with differential, platelet count, liver enzymes, blood pressure, heart rate, height, weight,
appetite, abnormal movements, growth in children. Patients should be re-evaluated at appropriate intervals
to assess continued need of the medication. Observe for signs/symptoms of aggression or hostility,
depression, delusional thinking, hallucinations, or mania. Monitor for visual disturbances. Monitor for signs of
misuse, abuse, and addiction.

Transdermal system: Also monitor the application site for local adverse reactions and allergic contact
sensitization.

Mechanism of Action Mild CNS stimulant; blocks the reuptake of norepinephrine and dopamine into
presynaptic neurons; appears to stimulate the cerebral cortex and subcortical structures similar to
amphetamines

Pharmacodynamics
Onset of action (AAP, 2011):

Oral:

Immediate release formulations [chewable tablet, oral solution, tablet (Methylin®, Ritalin®)]: 20-60
minutes

Extended release formulations [Capsule (Metadate CD®, Ritalin LA®), tablets (Concerta®)]: 20-60
minutes

Sustained release tablet (Ritalin-SR®): 60-180 minutes

Transdermal (Daytrana®): 60 minutes

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Maximum effect: Oral:

Immediate release tablet: Within 2 hours

Sustained release tablet: Within 4-7 hours

Duration of action (AAP, 2011):

Oral:

Immediate release formulations [Chewable tablet, oral solution, immediate release tablet
(Methylin®, Ritalin®)]: 3-5 hours

Extended release capsule (Metadate CD®, Ritalin LA®): 6-8 hours

Extended release tablet (Concerta®): 12 hours

Sustained release tablet (Ritalin-SR®): 2-6 hours

Transdermal (Daytrana®): 11-12 hours

Pharmacokinetics (Adult data unless noted) Note: Values reported below based on pediatric
patient data or combined pediatric and adult data.

Absorption: Oral:

Immediate release products: Readily absorbed

Transdermal: Rate and extent of absorption is increased when applied to inflamed skin or exposed to
heat; transdermal absorption may increase with chronic therapy

Distribution: Vd: d-methylphenidate: 2.65 ± 1.11 L/kg; l-methylphenidate: 1.80 ± 0.91 L/kg

Protein binding: 15%

Metabolism: Hepatic via hydroxylation (de-esterification by carboxylesterase CES1A1) to ritalinic acid (alpha-
phenyl-2-piperidine acetic acid), which has little or no pharmacologic activity

Bioavailability:

Immediate release chewable tablets and oral solution: Bioequivalent to immediate release tablets

Extended release suspension (Quillivant™ XR): 95% (relative to immediate release oral solution)

Transdermal patch (Daytrana®): Lower first-pass effect compared to oral administration; thus, much
lower doses (on a mg/kg basis) given via the transdermal route may still produce higher AUCs,
compared to the oral route

Half-life:

Oral:

Immediate release formulations:

Chewable tablets, oral solution (Methylin®): 3 hours

Tablet (Ritalin®):

Children: 2.5 hours (range: 1.8-5.3 hours)

Adults: 3.5 hours (range: 1.3-7.7 hours)

Extended release formulations:

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Capsule:

Metadate CD®: 6.8 hours

Ritalin LA®:

Children: 2.4 hours (range: 1.5-4 hours)

Adults: 3.3 hours (range: 3-4.2 hours)

Tablet (Concerta®): 3.5 hours

Suspension (Quillivant™ XR): Children ≥9 years, Adolescents, and Adults: ~5 hours

Transdermal patch (Daytrana®): Children and Adolescents 6-17 years: 4-5 hours

Time to peak serum concentration:

Oral:

Immediate release formulations:

Chewable tablets, oral solution (Methylin®): 1-2 hours

Tablet (Ritalin®): Children: 1.9 hours (range: 0.3-4.4 hours)

Extended release formulations:

Capsule (Metadate CD®): 1.5 hours

Tablet:

Concerta®: 6-10 hours

Metadate ER®: Children: 4.7 hours (range: 1.3-8.2 hours)

Powder for oral suspension (Quillivant™ XR):

Children (9-12 years): 4 hours

Adolescents (13-15 years): 2 hours

Adults: 4 hours

Sustained release tablets (Ritalin SR®): Children: 4.7 hours (range: 1.3-8.2 hours)

Transdermal patch (Daytrana®): Children 6-17 years: 8-10 hours

Elimination: 90% of dose is eliminated in the urine as metabolites and unchanged drug; main urinary
metabolite (ritalinic acid) accounts for 80% of the dose; drug is also excreted in feces via bile

Additional Information Methylphenidate is a racemic mixture of d- and l-enantiomers; the

d-enantiomer is more active than the l-enantiomer. Treatment with methylphenidate should include “drug
holidays” or periodic discontinuation in order to assess the patient's requirements, decrease tolerance and
limit suppression of linear growth and weight. Medications used to treat ADHD should be part of a total
treatment program that may include other components such as psychological, educational, and social
measures. Concerta®, Metadate CD®, and Ritalin LA® are formulated to deliver methylphenidate in a
biphasic release profile; Concerta® is an osmotic controlled release formulation, with an immediate release
(within 1 hour) outer coating; once daily Concerta® has been shown to be as effective as immediate release
methylphenidate tablets administered 3 times/day (Pelham, 2001). Metadate CD® capsules contain both
immediate release beads (30% of the dose) and extended release beads (70% of the dose). Ritalin LA®
capsules contain both immediate release beads (50% of the dose) and enteric coated, delayed release

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beads (50% of the dose). Methylin® and Ritalin-SR® tablets are color and additive free; Methylin® oral
solution is colorless. Concerta® tablets may be seen on abdominal x-ray under certain conditions (eg, when
digital enhancing techniques are used). Quillivant™ XR powder for oral suspension contains a combination
of uncoated and coated ion exchange resin complex and a buffering solution based on the Oral XR +
platform (Wigal, 2013). Once reconstituted with water forms an extended release suspension that contains
approximately 20% immediate release and 80% extended release methylphenidate.

Daytrana™ Transdermal System consists of an adhesive-based matrix containing active drug which is
dispersed in acrylic adhesive that is dispersed in a silicone adhesive. The patch consists of 3 layers: A
polyester/ethylene vinyl acetate laminate (outside) film backing, the adhesive layer containing
methylphenidate, and a flouropolymer-coated polyester protective liner (which must be removed before
application). Long-term use of the transdermal system or Concerta® >7 weeks, Metadate® CD >3 weeks,
and Ritalin LA® >2 weeks have not been adequately studied; long-term usefulness should be periodically
re-evaluated for the individual patient.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

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