KOMBOGLYZE Film-coated tablet Ref.[10497] Active ingredients: Metformin Metformin and Saxagliptin Saxagliptin

Posology

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

For patients inadequately controlled on maximal tolerated dose of metformin monotherapy

Patients not adequately controlled on metformin alone should receive a dose of this medicinal product equivalent to the total daily dose of saxagliptin 5 mg, dosed as 2.5 mg twice daily, plus the dose of metformin already being taken.

For patients switching from separate tablets of saxagliptin and metformin

Patients switching from separate tablets of saxagliptin and metformin should receive the doses of saxagliptin and metformin already being taken.

For patients inadequately controlled on dual combination therapy of insulin and metformin, or for patients controlled on triple combination therapy of insulin, and metformin plus saxagliptin as separate tablets

The dose of this medicinal product should provide saxagliptin 2.5 mg twice daily (5 mg total daily dose) and a dose of metformin similar to the dose already being taken. When this medicinal product 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 patients inadequately controlled on dual combination therapy of a sulphonylurea and metformin, or for patients switching from triple combination therapy of saxagliptin, metformin and a sulphonylurea taken as separate tablets

The dose of this medicinal product should provide saxagliptin 2.5 mg twice daily (5 mg total daily dose), and a dose of metformin similar to the dose already being taken. When this medicinal product 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 of dapagliflozin and metformin, or for patients switching from triple combination therapy of saxagliptin, metformin and dapagliflozin taken as separate tablets

The dose of this medicinal product should provide saxagliptin 2.5 mg twice daily (5 mg total daily dose), and a dose of metformin similar to the dose already being taken.

Special populations

Renal impairment

No dose adjustment is recommended for patients with mild renal impairment (GFR 60-89 mL/min).

A GFR should be assessed before initiation of treatment with metformin containing 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 Komboglyze in patients with GFR <60 mL/min.

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

Table 1. Dosage in patients with renal impairment:

Hepatic impairment

This medicinal product must not be used in patients with hepatic impairment (see sections 4.3 and 4.5).

Elderly (≥65 years)

As metformin and saxagliptin are excreted by the kidney, this medicinal product should be used with caution in the elderly. Monitoring of renal function is necessary to prevent metformin-associated lactic acidosis, particularly in the elderly (see sections 4.3, 4.4 and 5.2).

Paediatric population

The safety and efficacy of this medicinal product in children and adolescents from birth to <18 years of age have not been established. No data are available.

Method of administration

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

No data are available with regard to overdose of Komboglyze.

Saxagliptin

Saxagliptin has been shown to be well-tolerated with no clinically meaningful effect on QTc interval or heart rate at oral doses up to 400 mg daily for 2 weeks (80 times the recommended dose). In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. Saxagliptin and its major metabolite can be removed by haemodialysis (23% of dose over 4 hours).

Metformin

High overdose or concomitant risks of metformin may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and metformin is haemodialysis.

3 years.

Store below 25°C.

Alu/Alu blister.

Pack sizes of 14, 28, 56 and 60 film-coated tablets in non-perforated blisters. Multipacks containing 112 (2 packs of 56) and 196 (7 packs of 28) film-coated tablets in non-perforated blisters.

60 × 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.