Sitagliptin-Plus Sandoz

Initial therapy in patients w/ type 2 DM when diet & exercise do not provide adequate glycemic control. Adjunct to diet & exercise to improve glycemic control in patients w/ type 2 DM in combination w/ insulin; inadequately controlled on metformin or sitagliptin alone, or those already being treated w/ sitagliptin & metformin combination; as part of triple combination therapy w/ sulfonylurea or PPARγ agonist (eg, thiazolidinediones).

Individualized dosage. Max sitagliptin dose: 100 mg daily. Initial therapy: Sitagliptin 50 mg/metformin HCl 500 mg bid. May be titrated up to sitagliptin 50 mg/metformin HCl 1,000 mg bid. Patient inadequately controlled on metformin monotherapy Usual starting dose: Sitagliptin 50 mg bid + metformin dose already taken. Patient inadequately controlled on sitagliptin monotherapy Usual starting dose: Sitagliptin 50 mg/metformin HCl 500 mg bid. May be titrated up to sitagliptin 50 mg/metformin HCl 1,000 mg bid. Patient switching from co-administration of sitagliptin & metformin Initiate w/ dose of sitagliptin & metformin already being taken. Patient inadequately controlled on dual combination therapy w/ any 2 of the following: Sitagliptin, metformin or sulfonylurea/PPARγ agonist/insulin Usual starting dose: Sitagliptin 50 mg bid. Determine starting dose of metformin based on glycemic control level & current metformin dose. Patient w/ GFR 60-89 mL/min Max daily dose: Sitagliptin 100 mg/metformin 3,000 mg, 45-59 mL/min Max daily dose: Sitagliptin 100 mg/metformin 2,000 mg, 30-44 mL/min Max daily dose: Sitagliptin 50 mg/metformin 1,000 mg, <30 mL/min Max daily dose: Sitagliptin 25 mg.

Should be taken with food: Must not be split or divided before swallowing.

Hypersensitivity. Acute or chronic metabolic acidosis including lactic & diabetic ketoacidosis w/ or w/o coma. Diabetic pre-coma. Acute conditions w/ potential to alter renal function eg, dehydration, severe infection, shock. Intravascular administration of iodinated contrast materials (temporarily discontinue treatment) in patients undergoing radiologic studies. Acute or chronic disease which may cause tissue hypoxia eg, cardiac or resp failure, recent MI, shock. Acute alcohol intoxication, alcoholism. Severe renal failure (GFR <30 mL/min). Hepatic impairment. Lactation.

Discontinue use if hypersensitivity reaction; pacreatitis; lactic acidosis; bullous pemphigoid is suspected; at time of surgery under general, spinal or epidural anaesth; at the time of, or prior to, iodinated contrast imaging procedure in patients w/ eGFR ≥30 to <60 mL/min/1.73 m² & not restarted until at least 48 hr after; in patients w/ history of liver disease, alcoholism or heart failure; if ketoacidosis or lactic acidosis occurs. Temporarily discontinue metformin in case of dehydration (severe vomiting, diarrhoea, fever or reduced fluid intake); conditions w/ potential to alter renal function. Not to be used in type 1 diabetes & diabetic ketoacidosis; patients w/ GFR <30 mL/min. Not to restart treatment if acute pancreatitis is confirmed. Anaphylaxis, angioedema, & exfoliative skin conditions including SJS. Acute pancreatitis, persistent, severe abdominal pain; necrotising or haemorrhagic pancreatitis. Lactic acidosis at acute worsening of renal function or cardio-resp illness or sepsis; increased risk by metformin accumulation. Hypoglycaemia in combination w/ sulphonylurea or insulin. Dizziness & somnolence. Patients w/ history of pancreatitis. Metformin-treated patients w/ medicinal products that can acutely impair renal function eg, antihypertensives, diuretics & NSAIDs. Assess GFR before treatment initiation & at least annually thereafter & more frequently (every 3-6 mth) in patients at increased risk of renal impairment progression & in elderly. Promptly evaluate for evidence of ketoacidosis or lactic acidosis including serum electrolytes & ketones, blood glucose & pH, lactate, pyruvate, & metformin levels in patients w/ lab abnormalities or clinical illness. May affect ability to drive & use machines. Not recommended in patients w/ eGFR ≥30 & <45 mL/min/1.73 m². Not to be used in hepatic impairment. Not to be used during pregnancy & lactation. Not to be used in childn & adolescents 10-17 yr. Childn <10 yr. Elderly (monitor renal function).

Hypoglycemia. Monocomponents: Nausea, flatulence, vomiting. SJS. Sitagliptin: Headache, dizziness, URTI & nasopharyngitis. Metformin HCl: GI symptoms eg, diarrhoea, abdominal pain, loss of appetite. Metallic taste. Combination therapy: Constipation, peripheral oedema.

Increased risk of lactic acidosis w/ alcohol. Concomitant use w/ administration of iodinated contrast agents; local & systemic glucocorticoids, β2-agonists & diuretics. May decrease blood glucose levels w/ ACE inhibitors. Sitagliptin: Altered pharmacokinetics w/ potent CYP3A4 inhibitors ie, ketoconazole, itraconazole, ritonavir, clarithromycin in patients w/ severe renal impairment or ESRD. Increased plasma AUC & C_max of digoxin. Metformin HCl: May increase risk of lactic acidosis w/ NSAIDs including selective COX-II & ACE inhibitors, AIIA & diuretics (especially loop diuretics). Increased systemic exposure & risk of lactic acidosis w/ drugs that interfere w/ common renal tubular transport systems involved in renal elimination eg, organic cationic transporter-2 (OCT2)/multidrug & toxin extrusion (MATE) inhibitors eg, ranolazine, vandetanib, dolutegravir & cimetidine.

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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