JANUMET Film-coated tablet Ref.[10494] Active ingredients: Metformin Metformin and Sitagliptin Sitagliptin

Posology

The dose of antihyperglycaemic therapy with Janumet should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin.

Adults with normal renal function (GFR ≥90 mL/min)

For patients inadequately controlled on maximal tolerated dose of metformin monotherapy

For patients not adequately controlled on metformin alone, the usual starting dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken.

For patients switching from co-administration of sitagliptin and metformin

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 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 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 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 recommended diet with an adequate distribution of carbohydrate intake during the day.

Special populations

Renal impairment

No dose adjustment is needed for patients with mild renal impairment (glomerular filtration rate [GFR] ≥60 mL/min). A GFR should be assessed before initiation of treatment with metformincontaining products and at least annually thereafter. In patients at increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months.

The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. Factors that may increase the risk of lactic acidosis (see section 4.4) should be reviewed before considering initiation of metformin in patients with GFR <60 mL/min.

If no adequate strength of Janumet is available, individual monocomponents should be used instead of the fixed-dose combination.

Hepatic impairment

Janumet must not be used in patients with hepatic impairment (see section 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).

Paediatric population

Janumet should not be used in children and adolescents 10 to 17 years of age because of insufficient efficacy. Currently available data are described in sections 4.8, 5.1, and 5.2. Janumet has not been studied in paediatric patients under 10 years of age.

Method of administration

Janumet should be given twice daily with meals to reduce the gastrointestinal adverse reactions associated with metformin.

During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were administered. Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin. There is no experience with doses above 800 mg in clinical studies. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for periods of up to 28 days.

A large overdose of metformin (or co-existing risks of lactic acidosis) may lead to lactic acidosis which is a medical emergency and must be treated in hospital. The most effective method to remove lactate and metformin is haemodialysis.

In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour haemodialysis session. Prolonged haemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialysable by peritoneal dialysis.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required.

2 years.

Do not store above 30°C.

Opaque blisters (PVC/PE/PVDC and aluminium). Packs of 14, 28, 56, 60, 112, 168, 180, 196 film-coated tablets, multi-packs containing 196 (2 packs of 98) and 168 (2 packs of 84) film-coated tablets. Pack of 50 × 1 film-coated tablets in perforated unit dose blisters.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.