Sitagliptin, metformin hydrochloride.
SITA-Met Tablet 50/500 mg: Each film coated tablet contains: Sitagliptin phosphate monohydrate equivalent to Sitagliptin 50 mg, Metformin HCl B.P. 500 mg.
SITA-Met Tablet 50/1000 mg: Each film coated tablet contains: Sitagliptin phosphate monohydrate equivalent to Sitagliptin 50 mg, Metformin HCl B.P. 1000 mg.
Sita-Met (sitagliptin/metformin HCl) tablets contain two oral antihyperglycemic drugs used in the management of type 2 diabetes: sitagliptin and metformin hydrochloride.
Sitagliptin: Sitagliptin is an orally-active inhibitor of dipeptidyl peptidase-4 (DPP-4) enzyme. Sitagliptin is present in Sita-Met tablets in the form of sitagliptin phosphate monohydrate. Slows the inactivation of incretin hormones.
Metformin hydrochloride: Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents.
Pharmacology: Pharmacokinetics: Absorption: Sitagliptin: The absolute bioavailability of Sitagliptin is approximately 87%. Co-administration of a high-fat meal with Sitagliptin had no effect on the pharmacokinetics of Sitagliptin.
Metformin hydrochloride: The absolute bioavailability of Metformin hydrochloride 500-mg tablet given under fasting conditions is approximately 50-60%. Studies indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Food decreases the extent and slightly delays the absorption of Metformin. The clinical relevance of these decreases is unknown.
Distribution: Sitagliptin: The mean volume of distribution at steady state following a single 100-mg intravenous dose of Sitagliptin to healthy subjects is approximately 198 liters. The fraction of Sitagliptin reversibly bound to plasma proteins is low (38%).
Metformin hydrochloride: The apparent volume of distribution (V/F) of Metformin following single oral doses of Metformin hydrochloride tablets 850 mg averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound. Metformin partitions to erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of Metformin hydrochloride tablets, steady-state plasma concentrations of Metformin are reached within 24-48 hours and are generally <1 mcg/mL. During controlled clinical trials of metformin, maximum Metformin plasma levels did not exceed 5 mcg/mL, even at maximum doses.
Metabolism: Sitagliptin: Approximately 79% of Sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination.
Metformin hydrochloride: Metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans), nor biliary excretion.
Excretion: Sitagliptin: Sitagliptin is excreted through feces (13%) or urine (87%) within one week of dosing.
Elimination of Sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Metformin hydrochloride: Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of Metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.
Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes when treatment with both sitagliptin and metformin is appropriate.
Base dosage selection of sitagliptin/metformin on the patient's current dose of these agents (max, sitagliptin 100 mg/metformin 2,000 mg daily).
Patients Inadequately Controlled on Metformin Monotherapy: Adults: Start with sitagliptin 50 mg twice daily plus the current dose of metformin. For patients taking metformin 850 mg twice daily, the recommended starting dosage is sitagliptin 50 mg/metformin 1,000 mg twice daily.
Patients Inadequately Controlled on Sitagliptin Monotherapy: Adults: Start with sitagliptin 50 mg/metformin 500 mg twice daily. Titrate patient up to 50 mg/metformin 1,000 mg twice daily. Patients taking sitagliptin monotherapy whose dose has been adjusted for renal function impairment should not be switched to sitagliptin plus metformin.
Patients Inadequately Controlled on Dual Combination Therapy With Any 2 of the Following: Antihyperglycemic Agents: Sitagliptin, Metformin, or a Sulfonylurea: Adults: The usual starting dosage should provide sitagliptin dosed as 50 mg twice daily. In determining the starting dose of metformin, the patient's level of glycemic control and current dose, if any, of metformin should be considered. Gradual dose escalation to reduce the Gastro Intestinal adverse reactions associated with metformin should be considered. Patients currently receiving or initiating a sulfonylurea may require lower sulfonylurea doses to reduce the risk of hypoglycemia.
Patients Inadequately Controlled With Diet and Exercise Alone: Adults: Start with sitagliptin 50 mg/metformin 500 mg twice daily. Patients with inadequate glycemic control on this dosage can be titrated up to sitagliptin 50 mg/metformin 1,000 mg twice daily.
Patients Switching From Sitagliptin Coadministered with Metformin: Adults: Initiate therapy with dose of sitagliptin and metformin already being taken.
General Advice: In general, administer twice daily with meals.
Symptoms: Sitagliptin: Increased QTc intervals in sec (not considered clinically important).
Metformin: Hypoglycemia, lactic acidosis.
Renal disease or renal function impairment (eg, serum creatinine levels at least 1.5 mg/dL [males] and at least 1.4 mg/dL [females]); acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma; history of a serious hypersensitivity reaction, such as anaphylaxis or angioedema, to any component of the product.
Lactic acidosis, which is fatal in about 50% of cases, can occur. The risk increases with conditions such as acute CHF, dehydration, excess alcohol intake, hepatic and renal function impairment and sepsis. Symptoms include increasing somnolence, malaise, myalgia, non specific abdominal distress, and respiratory distress. Abnormal laboratory findings include elevated blood lactate, increased anionic gap, and low pH. If acidosis is suspected, discontinue drug and hospitalize the patient immediately.
Monitor: Measure blood glucose and glycosated hemoglobin (HbA1c) levels periodically; monitor hematologic parameters and renal function initially and at least annually thereafter.
Special Populations: Hypersensitivity: There have been reports of serious hypersensitivity reactions in patients treated with sitagliptin. Reactions include anaphylaxis, angioedema, and exfoliative skin conditions, including Steven-Johnson syndrome.
Renal Function: Contraindicated in patients with renal dysfunction. Metformin accumulation and lactic acidosis risk increases with the degree of renal function impairment.
Hepatic Function: Avoid metformin in patients with clinical or laboratory evidence of hepatic disease.
Special Risk Patients: Debilitated, malnourished, or elderly patients and patients with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in elderly patients, and in people who are taking beta-blocking agents.
Changes in clinical status: Promptly evaluate patients with previously well-controlled type 2 diabetes who develop laboratory abnormalities or clinical illness for ketoacidosis or lactic acidosis.
Hypoxic states: Immediately discontinue therapy in any condition characterized by hypoxemia (eg, acute HF, MI).
Loss of blood glucose control: Patients exposed to stress (e.g., fever, infection, surgery, trauma) may experience a loss in glycemic control. It may be necessary to withhold sitagliptin/metformin and temporarily administer insulin until an acute episode has been resolved.
Pancreatitis: If pancreatitis is suspected, promptly discontinue sitagliptin/metformin and initiate appropriate management.
Surgical patients: Temporarily suspend treatment for any surgical procedure, except in procedures not associated with restricted intake of food and fluids and do not restart treatment until oral intake has resumed and renal function has been evaluated as healthy.
Vitamin B12 levels: Metformin may decrease vitamin B12 levels.
Use in Pregnancy: Category B.
Use in Lactation: Metformin is excreted, but is considered compatible with breast-feeding; undetermined for sitagliptin.
Use in Children: Safety and efficacy not established.
Use in Elderly: Use with caution because of possible age-related reduction in renal function.
Pregnancy: Category B.
Lactation: Metformin is excreted, but is considered compatible with breast-feeding; undetermined for sitagliptin.
The following adverse reactions were reported with sitagliptin/metformin combination therapy.
Diarrhea, nausea, abdominal pain, vomiting, acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis.
Angioedema, cutaneous vasculitis, exfoliative skin conditions (including Stevens-Johnson syndrome), hypersensitivity (including anaphylaxis, rash, urticaria) (postmarketing).
Upper respiratory tract infection.
Hepatic enzyme elevations.
Alcohol: Hypoglycemic effects and the effects of metformin on lactic acidosis may be potentiated. Warn patients against excessive alcohol intake, acute or chronic, while receiving sitagliptin/metformin.
Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin): May compete with metformin for renal tubular transport. Although such interactions remain theoretical, careful patient monitoring and dose adjustment of sitagliptin/metformin and/or interfering drug is recommended in patients who are taking cationic medications excreted via the proximal renal tubular secretory system.
Cimetidine: Metformin plasma levels may be increased. Metformin pharmacologic effects and risk of adverse reactions may be increased. Monitor renal function closely. Dosage reduction may be needed during coadministration of cimetidine.
Cyclosporine: Co-administration of a single oral dose of sitagliptin 100 mg and cyclosporine 600 mg increased the AUC and Cmax of sitagliptin, AUC and Cmax may be increased. However, the magnitude of the change is not expected to be clinically important.
Digoxin: AUC and Cmax may be slightly increased. These increases are not likely to be clinically important.
Drugs that produce hyperglycemia (eg, calcium channel blockers, corticosteroids, diuretics [eg, thiazides], estrogens, hormonal contraceptives, isoniazid, nicotinic acid, phenothiazines, phenytoin, sympathomimetics, thyroid products): Closely monitor patient to maintain adequate glycemic control.
Food: Food may decrease the extent and slightly delay the absorption of metformin, as shown by a decrease in Cmax and AUC, and a prolongation of Tmax. Sitagliptin/metformin should be taken with food.
Furosemide: Metformin AUC and Cmax may be increased, while the AUC and Cmax of furosemide may be decreased. The renal clearance of furosemide and metformin are not changed.
Glyburide: Glyburide AUC and Cmax may be decreased. The clinical importance of this interaction is uncertain. Monitor blood glucose and, if an interaction is suspected, adjust the glyburide dose as needed.
Meglitinides (eg, nateglinide, repaglinide): May increase risk of hypoglycemia. A lower dose of the meglitinide may be needed to reduce the risk of hypoglycemia.
Nifedipine: Metformin AUC and Cmax may be increased.
NSAIDs (eg, indomethacin, rofecoxib): NSAIDs may decrease glomerular filtration, increasing metformin concentrations and the risk of lactic acidosis. Use with caution. Closely monitor renal function and for lactic acidosis. Lactic acidosis is a medical emergency that must be treated in a hospital setting. If an interaction is suspected, consider discontinuing the NSAID.
Parenteral iodinated contrast media: Risk of metformin-induced lactic acidosis may be increased. Temporarily discontinue metformin at the time of or prior to the procedure and withhold for 48 h subsequent to the procedure; reinstitute only after renal function has been reevaluated and found to be healthy.
Sulfonylureas: May increase risk of hypoglycemia. A lower dose of sulfonylurea may be needed to reduce the risk of hypoglycemia.
Store below 30°C.
Protect from heat, sunlight & moisture.
A10BD07 - metformin and sitagliptin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.
50/500 mg FC tab x 2 x 7's. 50/1,000 mg FC tab x 2 x 7's.