Gliptin

GLIPTIN 50: Yellow-brown film-coated, convex faces, round shape tablet, inscribed PCL on one side and half score on the other side.
Each tablet of GLIPTIN 50 contains Sitagliptin phosphate monohydrate equivalent to Sitagliptin 50 mg.
GLIPTIN 100: Yellow-brown film-coated, convex faces, round shape tablet, inscribed PCL on one side and half score on the other side.
Each tablet of GLIPTIN 100 contains Sitagliptin phosphate monohydrate equivalent to Sitagliptin 100 mg.

Pharmacology: Pharmacodynamics: Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4) enzyme resulting in prolonged active incretin levels. Incretin hormones (e.g., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production.
Pharmacokinetics: Absorption: Sitagliptin was rapidly absorbed, with peak plasma concentrations occurring 1 to 4 hours post-dose. The absolute bioavailability of sitagliptin is approximately 87%.
Distribution: The mean volume of distribution at steady state is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma protein is low (38%).
Metabolism: Not extensively metabolized; minor metabolism via CYP3A4 and CYP2C8 to metabolites (inactive).
Excretion: Approximately 87% were eliminated in urine (79% as unchanged drug, 16% as metabolites) and 13% were eliminated in feces, respectively. Half-life elimination is 12.4 hours.

Monotherapy: Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Combination with Metformin: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin as initial therapy or when the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with a Sulfonylurea: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a sulfonylurea when treatment with the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with a PPARγ agonist: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a PPARγ agonist (i.e., thiazolidinediones) as initial therapy or when the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with Metformin and a Sulfonylurea: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a sulfonylurea when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with Metformin and a PPARγ agonist: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a PPAR agonist (i.e., thiazolidinediones) when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with Insulin: Sitagliptin is indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin (with or without metformin).

100 mg once daily as monotherapy or as combination therapy with metformin, a sulfonylurea, insulin (with or without metformin), a PPARγ agonist (e.g., thiazolidinediones), metformin plus a sulfonylurea, or metformin plus a PPARγ agonist. Sitagliptin can be taken with or without food.
When Sitagliptin is used in combination with a sulfonylurea or with insulin, a lower dose of sulfonylurea or insulin may be considered to reduce the risk of sulfonylurea-or insulin-induced hypoglycemia.
Renal impairment: eGFR ≥60 mL/minute/1.73 m² to <90 mL/minute/1.73 m²: No dosage adjustment necessary.
eGFR ≥45 mL/minute/1.73 m² to <60 mL/minute/1.73 m²: No dosage adjustment necessary.
eGFR ≥30 mL/minute/1.73 m² to <45 mL/minute/1.73 m²: 50 mg once daily.
eGFR ≥15 mL/minute/1.73 m² to <30 mL/minute/1.73 m² or ESRD (eGFR <15 mL/minute/1.73 m²) requiring hemodialysis or peritoneal dialysis: 25 mg once daily and may be administered without regard to the timing of dialysis.
Hepatic impairment: Mild to moderate impairment (Child-Pugh classes A and B): No dosage adjustment.
Severe impairment (Child-Pugh class C): No dosage adjustment.

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 if required.

Sitagliptin is contraindicated in patients with known serious hypersensitivity (e.g., anaphylaxis, angioedema) to Sitagliptin or to any ingredient in the formulation.

Do not use in patient with known hypersensitivity to this medicine.
Do not use in type 1 diabetes treatment, patients with ketoacidosis, severe infection or serious accident.
Avoid to use in pregnancy and lactation.
Should not use concomitantly with alcohol.
This drug may increase risk of severe joint pain.

Genaral: Sitagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic and necrotizing pancreatitis associated with sitagliptin use. Monitor for signs/symptoms of pancreatitis. Discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis.
Use in Patients with Renal Impairment: Use with caution in patients with moderate to severe renal dysfunction and end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, dosing adjustment required.
Hypoglycemia in combination with a Sulfonylurea or with insulin: When Sitagliptin was used in combination with a sulfonylurea or insulin, the incidence of hypoglycemia was greater than that in patients receiving placebo with a sulfonylurea or insulin. Patients receiving sitagliptin may require a lower dosage of a concomitant insulin secretagogue (e.g., Sulfonylurea) or insulin to reduce the risk of hypoglycemia.
Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin reactions, such as Stevens-Johnson syndrome, have been reported. Discontinue if signs/symptoms of hypersensitivity reactions occur. Use with caution if patient has experienced angioedema with other DPP-4 inhibitor use.
Bullous Pemphigoid: DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.

Pregnancy: Category B.
There are no adequate and well-controlled studies in pregnant women; therefore, the safety of sitagliptin in pregnant women is not known. Sitagliptin, like other oral antihyperglycemic agents, is not recommended for use in pregnancy.
Lactation: Sitagliptin is secreted in the milk of lactating rats. It is not known whether sitagliptin is secreted in human milk. Therefore, sitagliptin should not be used by a woman who is nursing.

Endocrine & metabolic: Hypoglycemia.
Gastrointestinal: Hypoglycemia.
Renal: Increased serum creatinine.
Respiratory: Nasopharyngitis.
Rare: Postmarketing, and/or case reports: Acute pancreatitis (including hemorrhagic or necrotizing forms), acute renal failure (possibly requiring dialysis), anaphylaxis, angioedema, arthralgia, back pain, bullous pemphigoid, constipation, exfoliative dermatitis, headache, hypersensitivity angiitis, hypersensitivity reaction, increased liver enzymes, limb pain, myalgia, oral mucosa ulcer, pain, pemphigoid, pruritus, renal insufficiency, rhabdomyolysis, severe arthralgia, skin rash (including macular), Stevens-Johnson syndrome, stomatitis, urticaria, vomiting.

In drug interaction studies, sitagliptin did not have clinically meaningful effects on the pharmacokinetics of the following: metformin, rosiglitazone, glyburide (glybenclamide), simvastatin, warfarin, and oral contraceptives. Based on these data, sitagliptin does not inhibit CYP isozymes CYP3A4, CYP2C8, or CYP2C9. Based on in vitro data, sitagliptin is also not expected to inhibit CYP2D6, CYP1A2, CYP2C19 or CYP2B6 or to induce CYP3A4.
Population pharmacokinetic analyses have been conducted in patients with type 2 diabetes. Concomitant medications did not have a clinically meaningful effect on the pharmacokinetics of sitagliptin. Medications assessed were those that are commonly administered to patients with type 2 diabetes including cholesterol-lowering agents (e.g., statins, fibrates, ezetimibe), anti-platelet agents (e.g., clopidogrel), antihypertensives (e.g., ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, hydrochlorothiazide), analgesics and non-steroidal anti-inflammatory agents (e.g., naproxen, diclofenac, celecoxib), anti-depressants (e.g., bupropion, fluoxetine, sertraline), antihistamines (e.g., cetirizine), proton-pump inhibitors (e.g., omeprazole, lansoprazole), and medications for erectile dysfunction (e.g., sildenafil).
Patients receiving digoxin should be monitored appropriately. No dosage adjustment of digoxin or Sitagliptin is recommended.
No dosage adjustment is recommended when co-administered with cyclosporine or other p-glycoprotein inhibitors (e.g., ketoconazole).

Do not store above 30°C in well-closed container.

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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