Trevia

Sitagliptin (Trevia) 50 mg tablet is available as peach orange colored, round shaped biconvex film coated tablet, plain on both sides.
Sitagliptin (Trevia) 100 mg tablet is available as peach orange colored, round shaped biconvex film coated tablet, bisect line on side and plain on other side.
Sitagliptin (Trevia) is available for oral administration as: Each film-coated tablet contains: Sitagliptin (as phosphate), USP 50 mg and 100 mg.

Anti-Diabetic [Dipeptidyl Peptidase 4 (DPP-4) Inhibitor].
Pharmacology: Pharmacodynamics: Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones, including 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 insulin synthesis and release 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. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner.
Pharmacokinetics: Absorption: Following oral administration of a 100 mg dose, sitagliptin absorbs rapidly with peak plasma concentration (median T_max) occurring 1 to 4 hours post-dose, mean plasma AUC of sitagliptin is 8.52 μm·hr, with C_max 950 nM. The absolute bioavailability of sitagliptin is approximately 87%. Plasma AUC of sitagliptin increased in a dose-proportional manner and increased approximately 14% following 100 mg doses at steady-state compared to the first dose.
Distribution: The mean volume of distribution at steady state following a single 100 mg intravenous dose of sitagliptin is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Metabolism: Sitagliptin is primarily eliminated unchanged in urine (approximately 79%), and metabolism is a minor pathway. 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.
Excretion: Following administration of an oral [¹⁴C] sitagliptin dose, approximately 100% of the administered radioactivity eliminate in feces (13%) or urine (87%) within one week of dosing. The apparent terminal t_1/2 following a 100 mg oral dose of sitagliptin is approximately 12.4 hours and renal clearance is 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 (P-gp), which may also be involved in mediating the renal elimination of sitagliptin. However, cyclosporine, a P-gp inhibitor, did not reduce the renal clearance of sitagliptin.
Special Populations: Renal Insufficiency: Patients with mild renal insufficiency did not have a clinically meaningful increase in the plasma concentration of sitagliptin. The plasma AUC of sitagliptin increases approximately 2-fold in patients with moderate renal insufficiency, and an approximately 4-fold in patients with severe renal insufficiency and in patients with ESRD on hemodialysis. Sitagliptin was modestly removed by hemodialysis (13.5% over a 3 to 4 hour hemodialysis session starting 4 hours post dose). To achieve plasma concentration of sitagliptin similar to those in patients with normal renal function, lower dosages are recommended in patients with eGFR <45 mL/min/1.73 m².
Hepatic Insufficiency: There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score >9). However, because sitagliptin is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of sitagliptin.
Elderly: Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.
Type 2 diabetes: The pharmacokinetics of sitagliptin was generally similar in healthy subjects and in patients with type 2 diabetes.

Sitagliptin (Trevia) is indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control as: Monotherapy.
Dual Therapy: In combination with metformin HCl or with a sulphonylurea or with a PPARγ agonist (i.e., thiazolidinediones) when the treatment with the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Triple Therapy: In combination with metformin HCl and a sulphonylurea or with metformin HCl and a PPARγ (i.e., thiazolidinediones) when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with Insulin.

The recommended dose of Sitagliptin (Trevia) is 100 mg once daily as monotherapy or as combination therapy with metformin HCl, a sulphonylurea, insulin (with or without metformin HCl), a PPARγ agonist (i.e., thiazolidinediones), metformin HCl plus a sulphonylurea, or metformin HCl plus a PPARγ agonist (i.e., thiazolidinediones).
When Sitagliptin (Trevia) is used in combination with a sulphonylurea or with insulin, a lower dose of sulphonylurea or insulin may be considered to reduce the risk of sulphonylurea or insulin-induced hypoglycemia.
Co-administration of a high-fat meal with Sitagliptin (Trevia) had no effect on the pharmacokinetics, Sitagliptin (Trevia) maybe administered with or without food.
If a dose of Sitagliptin (Trevia) is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day or as prescribed by the physician.
Special Populations: Renal Insufficiency: For patients with mild renal insufficiency (creatinine clearance [Cl_Cr] >50 mL/min, approximately corresponding to serum creatinine levels of <1.7 mg/dL in men and <1.5 mg/dL in women), no dosage adjustment for sitagliptin is required. For patients with moderate renal insufficiency (Cl_Cr >30 to <50 mL/min, approximately corresponding to serum creatinine levels of >1.7 to <3.0 mg/dL in men and >1.5 to <2.5 mg/dL in women), the dose of sitagliptin is 50 mg once daily. For patients with severe renal insufficiency (Cl_Cr <30 mL/min, approximately corresponding to serum creatinine levels of >3.0 mg/dL in men and >2.5 mg/dL in women) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dose of sitagliptin is 25 mg once daily. Sitagliptin may be administered without regard to the timing of hemodialysis.
Elderly: No dose adjustment is required based on age.

Single dose of up to 800 mg of sitagliptin are generally well tolerated. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status.
Sitagliptin is modestly dialyzable. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Sitagliptin is contraindicated in: Patients with known hypersensitivity to sitagliptin or any of the components of the product; patients with type 1 diabetes or for the treatment of diabetic ketoacidosis; children below 18 years of age.

Pancreatitis: After initiation of sitagliptin, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, sitagliptin should promptly be discontinued and appropriate management should be initiated.
Hypoglycemia in combination with a sulfonylurea or with insulin: Sitagliptin as monotherapy and as part of combination therapy with agents not known to cause hypoglycaemia (i.e. metformin and/or a PPARγ agonist), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo. As is typical with other anti-hyperglycemic agents, hypoglycemia has been observed when sitagliptin was used in combination with insulin or a sulfonylurea. Therefore, to reduce the risk of sulfonylurea-or-insulin induced hypoglycemia, a lower dose of sulfonyl urea or insulin may be considered.

Pregnancy: The safety of sitagliptin in pregnant women is not known. Sitagliptin, like other oral antihyperglycemic agents, is not recommended for use in pregnancy.
Nursing Mother: It is not known whether sitagliptin is excreted in human milk. Because many drugs are excreted in human milk, sitagliptin should not be administered during nursing.

Headache, hypoglycemia, upper respiratory tract infection, nasopharyngitis, constipation, pruritus, pain in extremities, hypersensitivity reactions including anaphylactic responses, interstitial lung disease, vomiting, acute pancreatitis, fatal and non-fatal haemorrhagic, necrotizing pancreatitis, angioedema, rash, urticarial, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome, bullous pemphigoid, arthralgia, myalgia, back pain, arthropathy, worsening renal function including acute renal failure (sometimes requiring dialysis).
Discontinue if symptoms of acute pancreatitis occur such as persistent, severe abdominal pain.

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

Store at temperatures not exceeding 30°C.
Protect from sunlight and moisture.

Antidiabetic Agents

A10BH01 - sitagliptin ; Belongs to the class of dipeptidyl peptidase 4 (DPP-4) inhibitors. Used in the treatment of diabetes.

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