99mm 99mm

Sitagliptin accumulates only minimally with multiple doses.

Elimination of Sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3) and p-glycoprotein, which
may be involved in the renal elimination of Sitagliptin.

Sitagliptin is primarily excreted unchanged in urine (approximately 79%), and metabolism is a minor
[SITAGLIPTIN USP] pathway of elimination. The apparent terminal half-life t 1/2 following a 100mg oral dose of Sitagliptin
is approximately 12.4 hours and renal clearance is approximately 350mL/min.
COMPOSITION
INDICATIONS
INOSITA 25 mg Tablet
Each film coated tablet contains: For adult patients with type 2 diabetes mellitus, INOSITA is indicated to improve glycemic control as
Sitagliptin…………..25 mg an adjunct to diet and exercise:
(as phosphate monohydrate) USP
INOSITA 50 mg Tablet Monotherapy
Each film coated tablet contains: In patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate
Sitagliptin…………..50 mg due to contraindications or intolerance.
(as phosphate monohydrate) USP
INOSITA 100 mg Tablet Dual oral therapy
Each film coated tablet contains: In combination with metformin or with a sulfonylurea or with a PPAR agonist (i.e. thiazolidinedione)
Sitagliptin…………..100 mg when the treatment with the single agent alone, with diet and exercise, does not provide adequate
(as phosphate monohydrate) USP glycemic control
(USP Specs.)
Triple oral therapy
DESCRIPTION In combination with metformin and a sulfonylurea or with metformin and a PPAR agonist (i.e.
INOSITA Tablets contain sitagliptin phosphate, an orally-active inhibitor of the dipeptidyl peptidase¬4 thiazolidinedione) when dual therapy with these agents, with diet and exercise, does not provide
(DPP-4) enzyme, used as an oral hypoglycemic agent in Type II diabetes mellitus. It is chemically adequate glycemic control
described as as 7-[(3R)-3-amino-1-oxo-4-(2,4,5¬trifluorophenyl) butyl]-5,6,7,8-tetrahydro-3-(trifluo-
romethyl)-1,2,4-triazolo[4,3-a]pyrazine phosphate (1:1)monohydrate. The molecular formula is Combination therapy with Insulin with or without metformin
C16H15F6N5O•H3PO4•H2O Inosita is also indicated as add-on to insulin (with or without metformin) when diet and exercise plus
stable dose of insulin do not provide adequate glycemic control.
CLINICAL PHARMACOLOGY Limitations of Use
Not suitable for use in type I diabetes mellitus or for the treatment of diabetic ketoacidosis.
Pharmacodynamics
DOSAGE AND ADMINISTRATION
Mechanism of Action
INOSITA (Sitagliptin) is an inhibitor of DPP-IV enzyme which is responsible for the inactivation of The dose is 100 mg sitagliptin once daily. When used in combination with metformin and/or a PPARγ
incretin hormones. Sitagliptin is believed to exert its actions in Type II Diabetes by increasing and agonist, the dose of metformin and/or PPARγ agonist should be maintained, and Sitagliptin
prolonging the action of incretin hormones including glucagon-like peptide-1 (GLP-1) and glucose-de- administered concomitantly.
pendent insulinotropic polypeptide (GIP).
GLP-1 and GIP are released by the intestine throughout the day, and levels are increased in response to When Sitagliptin is used in combination with a sulphonylurea or with insulin, a lower dose of the
a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an sulphonylurea or insulin may be considered to reduce the risk of hypoglycemia.
endogenous system involved in the physiologic regulation of glucose homeostasis. When blood If a dose of Sitagliptin is missed, it should be taken as soon as the patient remembers. A double dose
glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release should not be taken on the same day.
from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also
lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. Dose adjustment and dosing considerations in Special populations
By increasing and prolonging active incretin levels, Sitagliptin increases insulin release and decreases
glucagon levels in the circulation in a glucose-dependent manner. Renal Impairment
Dosage adjustment is recommended in patients with moderate or severe renal impairment and in
In patients with type 2 diabetes with hyperglycemia, these changes in insulin and glucagon levels lead patients with ESRD - End Stage Renal Disease.
to lower hemoglobin A1c (HbA1c) and lower fasting and postprandial glucose concentrations. For patients with mild renal impairment (creatinine clearance [ClCr] equal to or greater than 50ml/min
and below 80ml/min) no dosage adjustment for Sitagliptin is required. For patients with moderate renal
Pharmacokinetics impairment (ClCr 30 to <50 mL/min), the dose of Sitagliptin is 50 mg once daily. For patients with
severe renal impairment (ClCr <30 mL/min), or those with end-stage renal disease (ESRD) requiring
Absorption hemodialysis or peritoneal dialysis, the dose of Sitagliptin is 25mg once daily. Sitagliptin may be
Following oral administration of a 100mg dose, Sitagliptin absorbs rapidly with peak plasma administered without regard to the timing of hemodialysis.
concentration occurring 1 to 4 hours post-dose. The absolute bioavailability of Sitagliptin is
approximately 87%. Because co-administration of a high-fat meal with sitagliptin has no effect on the Hepatic Impairment
pharmacokinetics, Sitagliptin may be administered with or without food. Plasma AUC of Sitagliptin No dose adjustment is required for mild to moderate hepatic impairment (Child Pugh score 5-9). There
increases in a dose-proportional manner. is no clinical experience in patients with severe hepatic impairment (Child Pugh score greater than 9).
Distribution Method of administration
The mean volume of distribution at steady state following a single 100 mg intravenous dose of Sitagliptin should be swallowed whole and tablets should not be split, crushed, or chewed before
Sitagliptin is approximately 198 liters. The fraction of Sitagliptin reversibly bound to plasma proteins swallowing. Co administration of a high-fat meal with Sitagliptin had no effect on the pharmacokinet-
is low (38%). ics; Sitagliptin may be administered with or without food.
Metabolism CONTRAINDICATIONS
Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Approximately 79 % of sitagliptin is excreted unchanged in the urine. Hypersensitivity to Sitagliptin
Following a sitagliptin oral dose, approximately 16 % of the radioactivity was excreted as metabolites WARNINGS AND PRECAUTIONS
of sitagliptin. Six metabolites were detected at trace levels and are not expected to contribute to the
plasma DPP-4 inhibitory activity of sitagliptin. In vitro studies indicated that the primary enzyme Pancreatitis
responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8. There have been post-marketing reports of acute pancreatitis. After initiation of Sitagliptin, patients
should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected,
Excretion Sitagliptin should promptly be discontinued and appropriate management should be initiated. It is
Following administration of an oral sitagliptin dose to healthy subjects, approximately 100 % of the unknown whether patients with a history of pancreatitis are at increased risk for the development of
administered radioactivity was eliminated in faeces (13 %) or urine (87 %) within one week of dosing.
 99mm 99mm

pancreatitis while using Sitagliptin.

Nursing mothers
Severe and Disabling Arthralgia It is not known whether Sitagliptin is excreted in human milk. Caution should be exercised when
Severe and disabling arthralgia (joint pain) has been reported in patients taking DPP-4 inhibitors. administering Sitagliptin to nursing mothers.
Consider as a possible cause for severe joint pain and discontinue drug, if appropriate.
Pediatrics
Hypoglycemia The safety and efficacy of sitagliptin in children and adolescents under 18 years of age have not been
When Sitagliptin is used in combination with a sulfonylurea or with insulin, there is an increased risk established.
of hypoglycemia. Therefore a lower dose of sulfonylurea or insulin may be required.
Elderly
Renal Impairment No dose adjustment is necessary based on age.
Sitagliptin has NOT been found to be nephrotoxic in clinical trials. However, there have been post
marketing reports of worsening renal function, including acute renal failure sometimes requiring Renal impairment
dialysis. Assessment of renal function is recommended prior to initiating Sitagliptin and periodically Patients with mild renal impairment did not have a clinically meaningful increase in the plasma
thereafter. Dosage adjustment is recommended in patients with moderate or severe renal insufficiency concentration of Sitagliptin. The plasma AUC of Sitagliptin increases approximately 2-fold in patients
and in patients with ESRD - End Stage Renal Disease. with moderate renal impairment, and an approximately 4-fold in patients with severe renal impairment
and in patients with End Stage Renal Disease (ESRD) on hemodialysis.
Allergic and Hypersensitivity Reactions Dosage adjustment is required which is based upon renal function, assessment of renal function is
There have been post-marketing reports of serious allergic and hypersensitivity reactions in patients recommended prior to initiation of sitagliptin and periodically thereafter (See DOSAGE & ADMINIS-
treated with Sitagliptin such as anaphylaxis, angioedema, and exfoliative skin conditions including TRATION and WARNINGS & PRECAUTIONS)
Stevens-Johnson syndrome. In such cases, discontinuation of the drug should be considered.
Hepatic impairment
Effects on ability to drive and use machines In patients with moderate hepatic insufficiency (Child-Pugh score 7-9), no clinically meaningful
Sitagliptin has no or negligible influence on the ability to drive and use machines. However, when alternations in pharmacokinetics were noted.
driving or using machines, it should be taken into account that dizziness and somnolence has been
reported. There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score > 9).
In addition, patients should be alerted to the risk of hypoglycemia when Sitagliptin is used in However, because Sitagliptin is primarily eliminated renally, severe hepatic impairment is not expected
combination with a sulphonylurea or with insulin. Hypoglycemia symptoms such as weakness, to affect the pharmacokinetics of Sitagliptin.
confusion, loss of consciousness may impair the ability of patients to drive or use machines.
No dose adjustment is necessary for patients with mild to moderate hepatic impairment. (See
ADVERSE REACTIONS DOSAGE& ADMINISTRATION)

Immune System disorders OVER DOSAGE

Unknown frequency: Hypersensitivity reactions including anaphylactic responses
Metabolic & Nutrition disorders In the event of an overdose with INOSITA (Sitagliptin), employ the usual supportive measures, e.g.,
Common: Hypoglycemia remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including
Nervous System disorders obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical
Common: Headache status. Sitagliptin is modestly dialyzable. Approximately 13.5% of the dose can be removed over a 3 to
Uncommon: Dizziness 4 hour hemodialysis session starting 4 hours post-dose. Prolonged hemodialysis may be considered if
Respiratory, Thoracic & Mediastinal disorders clinically appropriate. It is not known if Sitagliptin is dialyzable by peritoneal dialysis.
Unknown frequency: Interstitial lung disease
Gastrointestinal disorders PRESENTATION
Uncommon: Constipation
Unknown frequency: Vomiting, Acute Pancreatitis, Fatal & non-fatal Hemorrhagic and Necrotizing Inosita 25mg : Pack of 10 Tablets.
Pancreatitis Inosita 50mg : Pack of 28 Tablets.
Skin and subcutaneous tissue disorders Inosita 100mg : Pack of 28 Tablets.
Uncommon: Pruritus
Unknown frequency: Angioedema, Rash, Urticaria, Cutaneous Vasculitis, Exfoliative skin conditions INSTRUCTIONS
including Stevens - Johnson syndrome, Bullous pemphigoid
Musculoskeletal and connective tissue disorders Use as advised by the physician.
Unknown frequency: Arthralgia, Myalgia, Back pain, Arthropathy Keep all medicines out of the reach of children.
To be sold on the prescription of a registered medical practitioner only.
Renal & Urinary disorders: Protect from light, heat and moisture.
Unknown frequency: Impaired renal function, acute renal failure Store below 30°C.
For suspected adverse drug reaction, email us at :
Some adverse reactions were reported more commonly in studies of combination use of Sitagliptin reports@[Link]
reports@[Link]
with other anti-diabetic drugs than in studies of Sitagliptin monotherapy. These include:
For more information on our products
call PharmAssist helpline 0800-82222
Hypoglycemia (frequency very common with the combination of sulphonylurea and metformin), Monday to Friday 9:00 am to 6:00 pm
Influenza (common with insulin (with or without metformin), or email us at : pharmassist@[Link]
Nausea and Vomiting (common with metformin),
Flatulence (common with metformin or pioglitazone),
Constipation (common with the combination of sulphonylurea and metformin), pharmassist@[Link]
Peripheral edema (common with pioglitazone or the combination of pioglitazone and metformin),
Somnolence and diarrhea (uncommon with metformin),

DI:INOA 04 04/2019
Dry mouth (uncommon with insulin (with or without metformin)

DRUG INTERACTIONS

Digoxin
Sitagliptin has a small effect on plasma digoxin concentrations. No dosage adjustment of digoxin or
Sitagliptin is recommended. However, patients should be monitored for digoxin toxicity when
Sitagliptin and digoxin are administered concomitantly.

USE IN SPECIAL POPULATIONS

Pregnancy
US FDA Pregnancy category B. The safety of Sitagliptin in pregnant women is not known. Sitagliptin
should be avoided in pregnancy, unless clearly needed.