For patients switching from co-administration of sitagliptin and metformin, Janumet should be initiated at the dose of sitagliptin and metformin already being taken.

For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a sulphonylurea

The dose of Janumet should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken. When Janumet is used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be required to reduce the risk of hypoglycaemia (see section 4.4).

For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a PPARγ agonist

The dose of Janumet should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken.

For patients inadequately controlled on dual combination therapy with insulin and the maximal tolerated dose of metformin

The dose of Janumet should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken. When Janumet is used in combination with insulin, a lower dose of insulin may be required to reduce the risk of hypoglycaemia (see section 4.4).

For the different doses on metformin, Janumet is available in strengths of 50 mg sitagliptin and 850 mg metformin hydrochloride or 1,000 mg metformin hydrochloride.

All patients should continue their diet with an adequate distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.

Special populations

Renal impairment

Janumet should not be used in patients with moderate or severe renal impairment (creatinine clearance < 60 ml/min) (see sections 4.3 and 4.4).

Hepatic impairment

Janumet should not be used in patients with hepatic impairment (see sections 4.3 and 5.2).

Elderly

As metformin and sitagliptin are excreted by the kidney, Janumet should be used with caution as age increases. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly (see sections 4.3 and 4.4). Limited safety data on sitagliptin is available in patients > 75 years of age and care should be exercised.

Paediatric population

Janumet is not recommended for use in children below 18 years of age due to a lack of data on its safety and efficacy in this population.

Method of administration

Janumet should be given twice daily with meals to reduce the gastrointestinal undesirable effects associated with metformin.

4.3 Contraindications

 Janumet is contraindicated in patients with:

- hypersensitivity to the active substances or to any of the excipients (see sections 4.4 and 4.8);

- diabetic ketoacidosis, diabetic pre-coma;

- moderate and severe renal impairment (creatinine clearance < 60 ml/min) (see section 4.4);

- acute conditions with the potential to alter renal function such as:

      - dehydration,

      - severe infection,

      - shock,

      - int