Velmetia

Initial therapy in patients w/ 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 patients w/ type 2 DM inadequately controlled on metformin or sitagliptin alone or in patients already being treated w/ combination of sitagliptin & metformin; patients w/ type 2 DM in combination w/ insulin. As part of triple combination therapy w/ sulfonylurea as adjunct to diet & exercise in patients w/ type 2 DM inadequately controlled w/ any 2 of the 3 agents: metformin, sitagliptin, or a sulfonylurea; w/ PPARγ agonist (ie, thiazolidinediones) as adjunct to diet & exercise in patients w/ type 2 DM inadequately controlled w/ any 2 of the 3 agents: metformin, sitagliptin, or a PPARγ agonist.

Dose should be individualized while not exceeding max daily sitagliptin dose of 100 mg. Patient w/ type 2 DM whose hyperglycemia is inadequately controlled w/ diet & exercise alone Starting dose: 50 mg sitagliptin/500 mg metformin HCl bid. Dose may be titrated gradually in patient w/ inadequate glycemic control on this dose up to max daily metformin dose of 2,000 mg. Patient inadequately controlled on metformin monotherapy Total daily starting dose: 50 mg sitagliptin bid (100 mg total daily dose) + previously prescribed dose of metformin. Patient inadequately controlled on sitagliptin monotherapy Starting dose: 50 mg sitagliptin/500 mg metformin HCl bid. Dose may be titrated up to 50 mg sitagliptin/1 g metformin HCl bid. Patient switching from co-administration of sitagliptin & metformin May be initiated at previously prescribed dose of sitagliptin & metformin. Patient inadequately controlled on dual combination therapy w/ any 2 of the 3 antihyperglycemics: sitagliptin, metformin or a sulfonylurea Usual starting dose should provide sitagliptin dosed as 50 mg bid (100 mg total daily dose). To determine starting dose of metformin, consider patient's level of glycemic control & current dose (if any) of metformin. Patient currently on or initiating a sulfonylurea may require lower sulfonylurea doses. Patient inadequately controlled on dual combination therapy w/ any 2 of the 3 antihyperglycemics: sitagliptin, metformin or a PPARγ agonist (ie, thiazolidinediones) Usual starting dose should provide sitagliptin dosed as 50 mg bid (100 mg total daily dose). To determine starting dose of metformin, consider patient's level of glycemic control & current dose (if any) of metformin. Patient inadequately controlled on dual combination therapy w/ any 2 of the 3 antihyperglycemics: sitagliptin, metformin or insulin Usual starting dose should provide sitagliptin dosed as 50 mg bid (100 mg total daily dose). To determine starting dose of metformin, consider patient's level of glycemic control & current dose (if any) of metformin. Patient currently on or initiating insulin therapy may require lower insulin doses.

Should be taken with food.

Hypersensitivity. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, w/ or w/o coma. Severe renal impairment (eGFR <30 mL/min/1.73 m²).

Discontinue use if hypersensitivity reaction, pancreatitis or bullous pemphigoid is suspected; when CV collapse (shock) from whatever cause, acute CHF, acute MI & other conditions characterized by hypoxemia occur. Discontinue treatment at the time of, or prior to, an intravascular iodinated contrast imaging procedure in patients w/ eGFR ≥30 to <60 mL/min/1.73 m², those w/ history of liver disease, alcoholism or heart failure, or those who will be administered intra-arterial iodinated contrast; re-evaluate eGFR 48 hr after imaging procedure; restart treatment if renal function is acceptable. Should not be used in patients w/ type 1 diabetes or for treatment of diabetic ketoacidosis. Assess renal function before initiation of therapy & at least annually thereafter; assess more frequently in patients in whom development of renal dysfunction is anticipated & discontinue if evidence of renal impairment is present. Temporarily suspend use for any surgery (except minor procedures not associated w/ restricted intake of food & fluids) & do not restart until oral intake has resumed & renal function has been acceptable. Evaluate promptly for evidence of ketoacidosis or lactic acidosis in patient w/ type 2 diabetes previously well controlled on Velmetia who develops lab abnormalities or clinical illness (especially vague & poorly defined illness). W/hold treatment & temporarily administer insulin when loss of glycemic control occurs in patient stabilized on any diabetic regimen who is exposed to stress eg, fever, trauma, infection, or surgery; reinstitute after acute episode is resolved. Caution against excessive (acute or chronic) alcohol intake during treatment. Consider lower dose of concomitant sulfonylurea or insulin to reduce sulfonylurea or insulin-induced hypoglycemia. Possible interference w/ vit B₁₂ absorption; measure haematological parameters annually; investigate & manage appropriately any apparent abnormalities. Avoid use in patients w/ clinical or lab evidence of hepatic disease. Not recommended in patients w/ eGFR ≥30 mL/min/1.73 m² & <45 mL/min/1.73 m². Not recommended in pregnancy. Should not be used by nursing women. Studies do not support use in ped patients 10-17 yr w/ type 2 diabetes. Use in ped patients <10 yr has not been studied. Use w/ caution in the elderly. Metformin HCl: Risk of lactic acidosis due to metformin accumulation during treatment; discontinue immediately in patient w/ lactic acidosis. Risk of hypoglycemia in deficient caloric intake, strenuous exercise not compensated by caloric supplementation, or during concomitant use w/ other glucose-lowering agents (eg, sulfonylureas & insulin) or ethanol; elderly, debilitated, or malnourished patients, & those w/ adrenal or pituitary insufficiency or alcohol intoxication. Caution in concomitant use w/ medication(s) that may affect renal function or result in significant hemodynamic change or may interfere w/ disposition of metformin eg, cationic drugs eliminated by renal tubular secretion.

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; URTI, cough, fungal skin infection, peripheral edema. Sitagliptin in combination w/ metformin & insulin: Hypoglycemia; vomiting.

Metformin HCl: Decreased AUC & C_max of glyburide. Increased plasma & blood C_max & blood AUC w/ furosemide. Decreased C_max & AUC, & terminal t_1/2 of furosemide. Increased plasma C_max & AUC, & amount excreted in urine w/ nifedipine. Systemic exposure to metformin may be increased & risk for lactic acidosis increased 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/ drugs that tend to produce hyperglycemia eg, 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.

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