Janumet XR

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

Individualized dosage. Max daily dose: Sitagliptin 100 mg/metformin HCl 2,000 mg. Patient inadequately controlled w/ diet & exercise alone Total daily starting dose: Sitagliptin 100 mg/metformin HCl 1,000 mg, may be titrated gradually up to max daily metformin dose of 2,000 mg. Patient inadequately controlled on metformin monotherapy Total daily starting dose: Sitagliptin 100 mg + previously prescribed metformin dose. Patient inadequately controlled on sitagliptin monotherapy Starting dose: Sitagliptin 100 mg/metformin HCl 1,000 mg, may be titrated as needed to achieve glycemic control. Patient switching from co-administration of sitagliptin & metformin May be initiated w/ previously prescribed dose of sitagliptin & metformin. Patient inadequately controlled on dual combination therapy w/ any 2 of the following 3 antihyperglycemic agents: Sitagliptin, metformin or sulfonylurea Total daily starting dose: Sitagliptin 100 mg + metformin dose based on glycemic control level. Gradual dose escalation to reduce GI effects associated w/ metformin. Patients currently on or initiating sulfonylurea may require lower sulfonylurea doses to reduce risk of hypoglycemia. Patient inadequately controlled on dual combination therapy w/ insulin & metformin Total daily starting dose: Sitagliptin 100 mg + metformin dose based on glycemic control level. Gradual dose escalation to reduce GI effects associated w/ metformin. Patients currently on or initiating insulin may require lower insulin doses to reduce risk of hypoglycemia. Renal impairment (eGFR <45 mL/min/1.73 m²) Max sitagliptin dose: 50 mg once daily.

Should be taken with food: Take w/ meals preferably in the evening. Do not split/break/crush/chew tab before swallowing.

Hypersensitivity. Acute or chronic metabolic acidosis including diabetic ketoacidosis w/ or w/o coma. Temporarily discontinue use in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials which may result in acute renal function alteration. Severe renal impairment (eGFR <30 mL/min/1.73 m²).

Discontinue use if hypersensitivity reaction (including anaphylaxis, angioedema & exfoliative skin conditions including SJS) is suspected, assess for other potential causes & institute alternative diabetes treatment. Not to be used in patients w/ type 1 diabetes or for the treatment of diabetic ketoacidosis. Rarely, lactic acidosis may occur; discontinue use if acidosis is suspected & immediately hospitalize patient. Possible acute pancreatitis including fatal & non-fatal hemorrhagic or necrotizing pancreatitis. Promptly discontinue use & initiate appropriate treatment if pancreatitis is suspected. Patient w/ history of pancreatitis. Assess renal function before therapy initiation & at least annually thereafter. Assess renal function more frequently in patients whom development of renal dysfunction is anticipated, particularly in the elderly patients & discontinue use if evidence of renal impairment is present. Possible hypoglycemia in combination w/ sulfonylurea or insulin. Discontinue use if bullous pemphigoid is suspected; development of blisters or erosions while on treatment should be reported by the patient. Not recommended in patients w/ eGFR ≥30 mL/min/1.73 m² & <45 mL/min/1.73 m². Increased risk of lactic acidosis in patients w/ CHF requiring pharmacologic management particularly those w/ unstable or acute CHF at risk of hypoperfusion & hypoxemia. Promptly w/hold in presence of any condition associated w/ hypoxemia, dehydration or sepsis. Excessive acute or chronic alcohol intake. Temporarily suspend therapy prior to surgical procedure until resumption of oral intake & acceptable renal function. Prompt hemodialysis is recommended to correct acidosis & remove accumulated metformin. Particular susceptibility to hypoglycemic effects in elderly, debilitated or malnourished patients & those w/ adrenal or pituitary insufficiency or alcohol intoxication. Concomitant medications affecting renal function of or may result in significant hemodynamic change or may interfere w/ metformin disposition eg, cationic drugs that are eliminated by renal tubular secretion. Temporarily discontinue at the time of or prior to the procedure in patients w/ eGFR ≥30 to <60 mL/min/1.73 m², history of hepatic impairment, alcoholism, or heart failure who will be administered w/ intra-arterial iodinated contrast, & w/hold for 48 hr subsequent to the procedure & reinstitute after renal function has been re-evaluated to be acceptable. Promptly discontinue in the event of CV collapse from whatever cause, acute CHF or MI & other conditions characterized by hypoxemia. Annually measure hematologic parameters in patients on Janumet XR. Measure vit B₁₂ levels at 2-3 yr intervals in patients predisposed to developing subnormal vit B₁₂ levels. Promptly evaluate patients previously controlled on Janumet XR who develop lab abnormalities or clinical illness for evidence of ketoacidosis or lactic acidosis. W/hold treatment & temporarily administer insulin when patient is exposed to stress eg, fever, trauma, infection, or surgery due to potential temporary loss of glycemic control. Possible severe & disabling arthralgia; consider discontinuation if appropriate. Avoid in patients w/ clinical or lab evidence of hepatic disease. Not recommended during pregnancy. Not to be used during lactation. Childn <18 yr. Elderly.

Diarrhea, URTI, headache, nausea, vomiting, abdominal pain; hypoglycemia. Sitagliptin: Nasopharyngitis. Metformin HCl: Flatulence, abdominal discomfort indigestion, asthenia.

Sitagliptin: May increase plasma AUC & C_max of digoxin. Metfomin HCl: Increased plasma & blood C_max & AUC w/ furosemide. Enhanced absorption w/ nifedipine. May increase systemic exposure of metformin & risk for lactic acidosis in concomitant use w/ drugs that interfere w/ common renal tubular transport systems involved in the renal elimination of metformin [eg, organic cationic transporter-2/multidrug & toxin extrusion inhibitors (eg, ranolazine, vandetanib, dolutegravir & cimetidine)]. May lead to loss of glycemic control w/ thiazides & other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, OCs, phenytoin, nicotinic acid, sympathomimetics, Ca channel blockers & INH.

Antidiabetic Agents

A10BD07 - metformin and sitagliptin ; Belongs to the class of combinations of oral blood glucose lowering drugs. Used in the treatment of diabetes.

POM