PMS-SITAGLIPTIN-METFORMIN

1 Dosing Considerations  The dosage of pms-SITAGLIPTIN-METFORMIN should be individualized on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin and 2000 mg metformin hydrochloride.

Dose escalation should be gradual to reduce the gastrointestinal side effects associated with metformin use. Factors that may increase the risk of lactic acidosis should be reviewed before considering initiation of metformin-containing products in patients with renal impairment.

73 m2 is 50 mg and 1000 mg, respectively. , sulfonylurea), a lower dose of insulin or the insulin secretagogue may be considered to reduce the risk of hypoglycemia (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).  Concomitant Use with Medication(s) that May Decrease Renal Function Caution should be exercised when using concomitant medication(s) that may decrease renal function (like diuretics, particularly loop diuretics) or may interfere with the disposition of metformin, such as cationic drugs, that are eliminated by renal tubular secretion, due to the increased risk of developing lactic acidosis during co-administration (see 9 DRUG INTERACTIONS).

2 Recommended Dose and Dosage Adjustment pms-SITAGLIPTIN-METFORMIN is available in the following dosage strengths:  50 mg sitagliptin/500 mg metformin hydrochloride  50 mg sitagliptin/1000 mg metformin hydrochloride One pms-SITAGLIPTIN-METFORMIN tablet should be taken orally twice a day with meals to reduce the risk of gastrointestinal side effects associated with metformin use.

Tablets are to be swallowed whole. In patients on metformin (alone or in combination with a sulfonylurea, pioglitazone, or insulin), the recommended total daily dose of pms-SITAGLIPTIN-METFORMIN is 100 mg sitagliptin and the nearest therapeutically appropriate dose of metformin already being taken.

In patients already treated with sitagliptin and metformin, switching to pms-SITAGLIPTIN-METFORMIN may be initiated at the dose of sitagliptin and metformin already being taken.

Renal Impairment:

Renal function must be assessed prior to initiation of pms-SITAGLIPTIN-METFORMIN and periodically thereafter because there is a dosage adjustment based upon renal function. 73 m2 (see 7 WARNINGS AND PRECAUTIONS, Monitoring and Laboratory Tests).

57 pms-SITAGLIPTIN-METFORMIN (sitagliptin and metformin hydrochloride) Page 4 of 63 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS  pms-SITAGLIPTIN-METFORMIN (sitagliptin/metformin hydrochloride) is indicated for use as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin or in patients already being treated with the combination of sitagliptin and metformin.

 Add-on combination: pms-SITAGLIPTIN-METFORMIN is indicated for use as a triple combination therapy in adult patients with type 2 diabetes mellitus to improve glycemic control, in combination with: o sulfonylurea, o premixed or long/intermediate acting insulin o pioglitazone when the existing dual therapy with metformin, along with diet and exercise, does not provide adequate glycemic control (see 14 CLINICAL TRIALS).

1 Pediatrics  Pediatrics (<18 years of age): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of sitagliptin/metformin hydrochloride in pediatric patients has not been established; therefore, Health Canada has not authorized an indication for pediatric use.

2 Geriatrics  Geriatrics (≥65 years of age): pms-SITAGLIPTIN-METFORMIN should be used with caution in geriatric patients. Sitagliptin and metformin are substantially excreted by the kidney. Because aging can be associated with reduced renal function, care should be taken in dose selection and should be based on careful and regular monitoring of renal function (see 4 DOSING and ADMINISTRATION, 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism, and Special Populations).

2 CONTRAINDICATIONS  Unstable and/or insulin-dependent (type 1) diabetes mellitus.  Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma.  In patients with a history of lactic acidosis, irrespective of precipitating factors (see 7 WARNINGS AND PRECAUTIONS).

, Endocrine and Metabolism, and Special Populations). 2 CONTRAINDICATIONS  Unstable and/or insulin-dependent (type 1) diabetes mellitus.  Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma.

 In patients with a history of lactic acidosis, irrespective of precipitating factors (see 7 WARNINGS AND PRECAUTIONS). 73 m2)], end-stage renal disease, in patients on dialysis or when renal function is not known (see 7 WARNINGS AND PRECAUTIONS).

pms-SITAGLIPTIN-METFORMIN (sitagliptin and metformin hydrochloride) Page 5 of 63  In excessive alcohol intake, acute or chronic.  In patients suffering from severe hepatic dysfunction, since severe hepatic dysfunction has been associated with some cases of lactic acidosis, pms-SITAGLIPTIN-METFORMIN should not be used in patients with clinical or laboratory evidence of hepatic disease.

 In cases of cardiovascular collapse and in disease states associated with hypoxemia such as cardiorespiratory insufficiency, which are often associated with hyperlactacidemia.  During stress conditions, such as severe infections, trauma or surgery and the recovery phase thereafter.

 In patients suffering from severe dehydration or shock.  Known hypersensitivity to sitagliptin, metformin or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container (see 7 WARNINGS AND PRECAUTIONS and

 Unstable and/or insulin-dependent (type 1) diabetes mellitus.  Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma, history of ketoacidosis with or without coma.  In patients with a history of lactic acidosis, irrespective of precipitating factors (see 7 WARNINGS AND PRECAUTIONS).

73 m2)], end-stage renal disease, in patients on dialysis or when renal function is not known (see 7 WARNINGS AND PRECAUTIONS). pms-SITAGLIPTIN-METFORMIN (sitagliptin and metformin hydrochloride) Page 5 of 63  In excessive alcohol intake, acute or chronic.

 In patients suffering from severe hepatic dysfunction, since severe hepatic dysfunction has been associated with some cases of lactic acidosis, pms-SITAGLIPTIN-METFORMIN should not be used in patients with clinical or laboratory evidence of hepatic disease.

 In cases of cardiovascular collapse and in disease states associated with hypoxemia such as cardiorespiratory insufficiency, which are often associated with hyperlactacidemia.  During stress conditions, such as severe infections, trauma or surgery and the recovery phase thereafter.

 In patients suffering from severe dehydration or shock.  Known hypersensitivity to sitagliptin, metformin or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container (see 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section.  During pregnancy and breastfeeding (see 7 WARNINGS AND PRECAUTIONS, Special populations).  During period around administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function (see 7 WARNINGS AND PRECAUTIONS).