Regulatory Class: ℞

Generic Name: Sitagliptin, Metformin HCl

Content: Per 50 mg/500 mg FC tab Sitagliptin phosphate monohydrate 64.25 mg (equiv to sitagliptin 50 mg as free base), metformin HCl 500 mg. Per 50 mg/1 g FC tab Sitagliptin phosphate monohydrate 64.25 mg (equiv to sitagliptin 50 mg as free base), metformin HCl 1 g

Indications or Uses Initial therapy in Type 2 DM to improve glycemic control when diet & exercise alone do not provide adequate glycemic control, or inadequately controlled w/ metformin or sitagliptin alone or in patients being treated w/ combination of metformin & sitagliptin. As part of triple combination therapy w/ a sulfonylurea as an adjunct to diet & exercise in patients w/ type 2 DM inadequately controlled w/ any 2 of the 3 agents: metformin, sitagliptin, or a sulfonylurea. As part of triple combination therapy w/ PPAR-γ agonist as an adjunct to diet & exercise in patients w/ type 2 DM inadequately controlled w/ any 2 of the 3 agents: metformin, sitagliptin, or a PPAR-γ agonist. Type 2 DM as an adjunct to diet & exercise to improve glycemic control in combination w/ insulin.

Dosage/Direction for Use: Individualized dosing. Initial therapy:For Patient with type 2 diabetes mellitus starting dose 50 mg/500 mg bid. May be titrated up to 50 mg/1 g twice daily. Patient inadequately controlled on metformin monotherapy Sitagliptin 50 mg twice daily +dose of metformin already taken. Patient inadequately controlled on sitagliptin monotherapy , usual starting dose of 50 mg/500 mg tab twice daily. May be titrated up to 50 mg/1 g tab bid. Patient inadequately controlled on dual combination therapy w/ any 2 of the following 3 antihyperglycemic agents: Sitagliptin, metformin or a PPAR-γ agonist (ie thiazolidinediones) Sitagliptin 50 mg bid (100 mg total daily dose). In determining the starter dose of the metformin component, the patient's level of glycemic control & current dose (if any) of metformin should be considered. Gradual dose escalation to reduce GI effects associated w/ metformin should be considered. Patient switching from sitagliptin co-administered w/ metformin Initiate w/ dose of sitagliptin & metformin already being taken. Patient inadequately controlled on dual combination therapy w/ any 2 of the following 3 antihyperglycemic agents: Sitagliptin, metformin or sulfonylurea Sitagliptin 50 mg twice daily (100 mg total daily dose) + metformin dose based on glycemic control level. Patients currently on or initiating sulfonylurea may require lower doses of sulfonylurea doses to reduce the risk of sulfonylurea-induced hypoglycemia. Gradual dose escalation to reduce GI effects associated w/ metformin should be considered. Patient inadequately controlled on dual combination therapy w/ any 2 of the following 3 antihyperglycemic agents: Sitagliptin, metformin or insulin Sitagliptin dose at 50 mg twice daily + metformin dose based on glycemic control level & current dose (if any) of metformin. Gradual dose escalation to reduce GI effects associated w/ metformin should be considered. Patients currently on or initiating insulin therapy may require lower doses of insulin to reduce the risk of hypoglycemia.

Administration: To take with food;

Contraindication:  Hypersensitivity to sitagliptin phosphate, metformin hydrochloride or any other component of SITAGLIPTIN + METFORMIN HCl. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Discontinue in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function. Severe renal impairment, (eGFR < 30 mL/min/1.73 m2). Pregnancy and lactation.

Special Precaution: Do not use in type 1 diabetes or treatment of diabetic ketoacidosis. Inform patients of the characteristic symptom of acute pancreatitis. Assess renal function before initiation of therapy & at least annually thereafter. Hypoglycemia in combination w/ sulfonylurea or insulin. Temporarily discontinue therapy at the time or prior the procedure & w/held 48 hr in patients who will be administered w/ intra-arterial iodinated contrast, w/ an eGFR ≥30-60 mL/min/1.73 m2, history of hepatic impairment,alcoholism, heart failure. Hypoxic states. Suspend therapy prior to surgical procedure until resumption of oral intake. Avoid excessive alcohol intake. Impaired hepatic function. Monitor vit B12 levels. Change in clinical status of patients w/ previously controlled type 2 diabetes. Loss of glycemic control may occur. Sitagliptin: Hypersensitivity. Discontinue if bullous pemphigoid is suspected. Metformin: Lactic acidosis. W/held in any condition associated w/ hypoxemia, dehydration or sepsis. Hypoglycemic effects in elderly, debilitated or malnourished patients, & those w/ adrenal or pituitary insufficiency or alcohol intoxication. Concomitant use of medications that may affect renal function. Children less than 18 yr. Elderly.

Adverse Reaction: Combination therapy w/ sitagliptin & metformin: Diarrhea, nausea, dyspepsia, flatulence, vomiting, headache, hypoglycemia; abdominal pain. Sitagliptin in combination w/ metformin & a sulfonylurea: Hypoglycemia & constipation. Sitagliptin in combination w/ metformin & a PPARγ agonist: Headache, diarrhea, nausea, hypoglycemia, vomiting; upper resp tract infection, cough, fungal skin infection, peripheral edema, vomiting. Sitagliptin in combination w/ metformin & insulin: hypoglycemia, vomiting.

Interactions: May lead to loss of glycemic control with drugs tend to produce hyperglycemia example thiazides and other diuretics, cortecosteroids,phenothiazines, thyroid products,estrogens, oral costercortiroids, phenytoin, nicotinic acid, sympathomimetics, Ca channel blocking drugs and Isoniazid. Sitagliptin: Increased AUC & Cmax w/ cyclosporine (a potent probe inhibitor of p-glycoprotein). Metformin HCl: Increased plasma & blood Cmax & blood AUC w/ furosemide. Increased plasma Cmax & AUC & increased amount excreted in the urine w/ nifedipine. Increased systemic exposure & risk for lactic acidosis w/ concomitant use of drugs that interfere w/ common renal tubular transport system (eg, organic cationic transporter-2 [OCT2]/multidrug & toxin extrusion [MATE] inhibitors eg, ranolazine, vandetanib, dolutegravir & cimetidine).

Presentation/Packaging: 50 mg/500 mg FC tab 28's & 50 mg/1 g FC tab 28's .

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