50 mg: Sitagliptin (as phosphate monohydrate) 50 mg Film Coated Tablet, a light pink, circular, bi-convex film coated tablet, engraved 'ACME' on one face and a break line on the other.
Each film-coated tablet contains: Sitagliptin Phosphate Monohydrate 64.25 mg equivalent to Sitagliptin 50 mg.
100 mg: Sitagliptin (as phosphate monohydrate) 100 mg Film Coated Tablet, a golden yellow, circular, bi-convex film coated tablet, engraved with 'ACME' on one face and the other side being plain.
Each film-coated tablet contains: Sitagliptin Phosphate Monohydrate 128.50 mg equivalent to Sitagliptin 100 mg.
Blood Glucose Lowering Drug (Dipeptidyl Peptidase 4 Inhibitor).
Pharmacology: Pharmacodynamics: Mechanism of action: Sitagliptin phosphate is an orally active, potent, and highly selective inhibitor of the dipeptidyl peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes. The DPP-4 inhibitors are a class of agents that act as incretion enhancers. By inhibiting the DPP-4 enzyme, sitagliptin increases the levels of two known active incretion hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase selective inhibitors of the enzyme DPP-4 and do not inhibit the closely related enzymes DPP-8 or DPP-9 at therapeutic concentrations. Sitagliptin differs in chemical structure and pharmacological action from GLP-1 analogs, insulin, sulfonylureas or meglitinides, biguanides, peroxisome proliferator-activated receptor gamma (PPAR) agonists, alpha-glucosidase inhibitors, and amylin analogs. In a two-day study in healthy subjects, sitagliptin alone increases active GLP-1 concentrations, whereas metformin alone increases active and total GLP-1 concentrations to similar extents. Co-administration of sitagliptin and metformin had an additive effect on active GLP-1 concentrations. Sitagliptin, but no metformin, increases active GIP concentrations.
Clinical efficacy and safety Overall: Sitagliptin improved glycemic control when used as monotherapy or in combination treatment in adult patients with type 2 diabetes. In clinical trials, sitagliptin as monotherapy improved glycemic control with significant reductions in hemoglobin A1c (HbA1c) and fasting and post-prandial glucose. Reduction in fasting plasma glucose (FPG) was observed at 3 weeks, the first time point at which FPG was measured. The observed incidence of hypoglycemia in patients treated with sitagliptin was similar to placebo. Body weight did not increase from baseline with sitagliptin therapy. Improvements in surrogate markers of beta cell function, including HOMA-β (Homeostasis Model Assessment-β), proinsulin to insulin ratio, and measures of beta cell responsiveness from the frequently sampled meal tolerance test were observed.
Pharmacokinetics: Absorption: Following oral administration of a 100-mg dose to healthy subjects, sitagliptin was rapidly absorbed, with peak plasma concentrations (median Tmax) occurring 1 to 4 hours post-dose, the mean plasma AUC of sitagliptin is 8.52 μm/h, Cmax is 950 nm. The absolute bioavailability of sitagliptin is approximately 87%. Since co-administration of a high-fat meal with sitagliptin did not affect the pharmacokinetics, it may be administered with or without food. Plasma AUC of sitagliptin increased in a dose-proportional manner. Dose-proportionality was not established for Cmax and C24hr (Cmax increased in a greater-than-dose-proportional manner and C24hr increased in a less-than-dose-proportional manner).
Distribution: The mean volume of distribution at steady state following a single 100-mg intravenous of sitagliptin to healthy subjects is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Biotransformation: Sitagliptin is primarily eliminated unchanged in the urine, and metabolism is a minor pathway. Approximately 79% of sitagliptin is excreted unchanged in the urine. Following a [14C] sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites 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 responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
In vitro, data showed that sitagliptin is not an inhibitor of CYP isozymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19, or 2B6 and is not an inducer of CYP3A4 and CYP1A2.
Elimination: Following administration of an oral [14C] sitagliptin dose to healthy subjects, approximately 100% of the administered radioactivity was eliminated in feces (13%) or urine (87%) within one week of dosing. The apparent terminal t1/2 following a 100-mg oral dose of sitagliptin was approximately 12.4 hours. Sitagliptin accumulates only minimally with multiple doses. The renal clearance was approximately 350 mL/min.
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), which may be involved in the renal elimination of sitagliptin. The clinical relevance of hOAT-3 in sitagliptin transport has not been established. Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin. However, ciclosporin, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin. Sitagliptin is not a substrate for OCR2, OAT1, or PEP1/2 transporters. In vitro, sitagliptin did not inhibit OAT3 (IC50=160 μM) or P-glycoprotein (up to 250 μM) mediated transport at therapeutically relevant plasma concentrations. In a clinical study, sitagliptin had a small effect on plasma digoxin concentration indicating that sitagliptin may be a mild inhibitor of p-glycoprotein.
Characteristics in patients: The pharmacokinetics of sitagliptin were generally similar in healthy subjects and in patients with type 2 diabetes.
Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is also indicated for use in combination with Metformin, Sulfonylurea, or Thiazolidinediones when diet and exercise plus the single agent do not provide adequate glycemic control.
The usual oral dose is the equivalent of 100 mg of Sitagliptin once daily as monotherapy or in combination. When given with metformin in a combination preparation, Sitagliptin may be given in 2 divided doses. The dose of sulfonylurea may need to be lowered when used with sitagliptin. Sitagliptin may be taken with or without food.
Or as directed by the physician.
In Phase I multiple-dose studies, as observed with Sitagliptin there were no dose-related clinical adverse reactions with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for periods of up to 28 days.
In the event of an overdose, the following supportive measures should be: Removal of unabsorbed material from the gastrointestinal tract; Clinical monitoring (including obtaining an electrocardiogram); Institute supportive therapy if required.
In clinical studies, Sitagliptin is modestly dialyzable, over a 3 to 4-hour hemodialysis session approximately 13.5% of it will be removed. If clinically relevant, prolonged hemodialysis sessions may be considered. Peritoneal dialysis is unidentified for Sitagliptin.
History of a serious hypersensitivity reaction to Sitagliptin, such as anaphylaxis or angioedema and exfoliative skin conditions including Stevens-Johnson syndrome.
If pancreatitis is suspected, Sitagliptin should promptly be discontinued and appropriate management should be initiated. Dosage adjustment should be recommended in patients with moderate or severe renal insufficiency and patients with ESRD. Assessment of renal function should be recommended before initiating Sitagliptin. When Sitagliptin is used in combination with sulfonylurea or with insulin, medications are known to cause hypoglycemia. If bullous pemphigoid is suspected, sitagliptin should be discontinued. If a hypersensitivity reaction is suspected, the use of Sitagliptin should be discontinued.
Pregnancy: Pregnancy Category B: The safety of Sitagliptin in pregnant women has not been established. Sitagliptin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing mother: It is not known whether Sitagliptin is excreted in human milk because many drugs are excreted in human milk. Caution should be exercised when Sitagliptin is administered to a nursing woman.
Adverse effects include upper respiratory tract infections, headaches, and nasopharyngitis. Hypersensitivity reactions including anaphylaxis, angioedema, urticaria, rash, and Stevens-Johnson syndrome have also been reported.
Co-administration of Digoxin and Sitagliptin for ten days may slightly increase the mean peak drug concentration of Digoxin. No dosage adjustment of Digoxin or Sitagliptin is recommended.
Special Precautions for Handling and Disposal: Any unused medicine should be disposed of properly. Consult the pharmacist or local waste management center for more details about how to safely discard expired or unused medicines.
Store at temperatures not exceeding 30°C.
A10BH01 - sitagliptin ; Belongs to the class of dipeptidyl peptidase 4 (DPP-4) inhibitors. Used in the treatment of diabetes.
Glipzeal FC tab 100 mg
30's
Glipzeal FC tab 50 mg
30's
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