Sitavia

Sitavia 50: Brownish-orange, round, biconvex, film-coated tablet with "50" on one side and break line on the other.
Each tablet contains Sitagliptin phosphate 64.25 mg eq. to Sitagliptin 50 mg.
Sitavia 100: Brownish-orange, round, biconvex, film-coated tablet with "100" on one side and break line on the other.
Each tablet contains Sitagliptin phosphate 128.5 mg eq. to Sitagliptin 100 mg.

Pharmacology: Pharmacodynamics: Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4), an enzyme that inactivates glucagon-like peptide (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), which are incretin hormones. The drug inhibits DPP-4 selectively with no effect on DPP-8 or DDP-9 in vitro at concentrations approximating those from therapeutic dosage. Sitagliptin increases circulating concentrations of GIP and GLP-1 in a glucose-dependent manner.
GIP and GLP-1 stimulate insulin synthesis and release from pancreatic B-cells in a glucose-dependent manner. GLP-1 also decreases glucagon secretion from pancreatic alpha-cells in a glucose-dependent manner, leading to reduced hepatic glucose production.
Sitagliptin lowers fasting plasma glucose concentrations and reduces glucose excursions following glucose load or meal in patients with type 2 diabetes mellitus.
Pharmacokinetics: Peak plasma sitagliptin concentration is achieved within 3 hours following oral administration. Absolute bioavailability is approximately 87%. Administration of sitagliptin with a high-fat meal had no effect on the pharmacokinetics of the drug. Sitagliptin is metabolized to a limited extent by CYP isoenzymes 3A4 and 2C8 to active metabolites. Terminal half-life of sitagliptin is 12.4 hours following oral administration of a 100 mg oral dose. Following administration of a single radiolabeled dose, 87% of the dose was excreted in the urine (mainly as unchanged drug) and 13% was excreted in the feces.

Monotherapy: SITAVIA is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Combination with Metformin: SITAVIA 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: SITAVIA 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: SITAVIA 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: SITAVIA 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: SITAVIA is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a PPARγ agonist (i.e., thiazolidinediones) when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with Insulin: SITAVIA 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).

Recommended Dose: The recommended dose of SITAVIA is 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.
When SITAVIA 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.
Patients with Renal Impairment: Because there is a dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of SITAVIA and periodically thereafter.
For patients with mild renal impairment (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m² to <90 mL/min/1.73 m²), no dosage adjustment for SITAVIA is required.
For patients with moderate renal impairment (eGFR ≥45 mL/min/1.73 m² to <60 mL/min/1.73 m²), no dosage adjustment for SITAVIA is required.
For patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m² to <45 mL/min/1.73 m²), the dose of SITAVIA is 50 mg once daily.
For patients with severe renal impairment (eGFR ≥15 mL/min/1.73 m² to <30 mL/min/1.73 m²) or with end-stage renal disease (ESRD) (eGFR <15 mL/min/1.73 m²), including those requiring hemodialysis or peritoneal dialysis, the dose of SITAVIA is 25 mg once daily.
SITAVIA may be administered without regard to the timing of dialysis.
Mode of Administration: Can be taken with or without food.

There is no experience with doses above 800 mg in clinical studies. 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 modestly dialyzable. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Contraindicated in patients who are hypersensitive to any components of this product.

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

Sitagliptin should not be used in type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis (DKA).
The dose of sitagliptin should be reduced in moderate and severe renal impairment.
Severe and disabling arthralgia has been reported with dipeptidyl peptidase-4 (DPP-4) inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of the therapy.
After bariatric surgery, closely monitor patients for signs and symptoms of pancreatitis.

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 distributed into milk in rats; it is known whether the drug is distributed into human milk, use with caution in lactation.

Adverse effects reported in at least 5% of patients receiving sitagliptin as monotherapy or add-on therapy with metformin and/or a thiazolidinedione or glimepiride and more commonly than with placebo include nasopharyngitis, upper respiratory tract infection, peripheral edema, and headache.
Adverse effects reported in at least 5% of patients receiving sitagliptin in combination with metformin and sulfonylurea (glimepiride) and more commonly than with placebo include hypoglycemia and headache.
Adverse effects reported in at least 5% of patients receiving sitagliptin in combination with insulin and more commonly than with placebo include hypoglycemia.

Drugs Metabolized by Hepatic Microsomal Enzymes: Sitagliptin is metabolized to a limited extent by cytochrome P-450 (CYP) isoenzymes 3A4 and 2C8 to inactive metabolites. Sitagliptin does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro or induce CYP3A4. Pharmacokinetic interactions with drugs metabolized by these isoenzymes are unlikely.
Drug Secreted by Renal Tubular Cationic Transport: Sitagliptin is a substrate of the organic anion transport system; pharmacokinetic interactions are unlikely with substrates of the organic cationic transport system.
Inhibitors of P-glycoprotein Transport System: Sitagliptin is a substrate of the P-glycoprotein transport system. There is a potential pharmacokinetic interaction (increased absorption and renal clearance of sitagliptin) with P-glycoprotein inhibitors.
Protein-bound Drugs: Pharmacokinetic interactions between sitagliptin and protein-bound drugs are unlikely.
Cyclosporine: Concomitant administration of cyclosporine and sitagliptin may increase absorption and plasma concentrations of sitagliptin. However, this interaction is not considered clinically important.
Digoxin: Concomitant administration of sitagliptin (100 mg daily for 10 days) with digoxin resulted in a slight increase in plasma concentrations and area under the concentration-time curve (AUC) of digoxin (18 and 11%, respectively). While these increases are not considered clinically important, patients receiving digoxin should be monitored appropriately; however, no digoxin or sitagliptin dosage adjustment is needed.
Hormonal Contraceptives, Oral: Sitagliptin has no clinically important effect on the pharmacokinetics of norethindrone or ethinyl estradiol.
Metformin: Sitagliptin and metformin have a potential additive effect on active glucagon-like peptide (GLP-1) concentrations. Pharmacokinetic interactions are unlikely.
The relevance of these effects to glycemic control in patients with type 2 diabetes mellitus is unclear.
Simvastatin: Pharmacokinetic interactions between sitagliptin and simvastatin are unlikely.
Sulfonylureas or Insulin: Clinically important pharmacokinetic interactions between sitagliptin and sulfonylureas (e.g. glimepiride, glipizide, glyburide, tolbutamide) are unlikely.
Thiazolidinediones: Pharmacokinetic interactions between sitagliptin and thiazolidinediones are unlikely.
Warfarin: Pharmacokinetic interactions between sitagliptin and warfarin are unlikely.

Store below 30°C, protect from moisture and light.

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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