XIGDUO Film-coated tablet Ref.[50780] Active ingredients: Dapagliflozin Metformin Metformin and Dapagliflozin

Posology

Adults with normal renal function (glomerular filtration rate [GFR] ≥90 mL/min)

The recommended dose is one tablet twice daily. Each tablet contains a fixed dose of dapagliflozin and metformin (see section 2).

For patients insufficiently controlled on metformin monotherapy or metformin in combination with other medicinal products for the treatment of diabetes

Patients insufficiently controlled on metformin alone or in combination with other medicinal products for the treatment of diabetes should receive a total daily dose of Xigduo equivalent to dapagliflozin 10 mg, plus the total daily dose of metformin, or the nearest therapeutically appropriate dose, already being taken. When Xigduo is used in combination with insulin or an insulin secretagogue such as sulphonylurea, a lower dose of insulin or sulphonylurea may be considered to reduce the risk of hypoglycaemia (see sections 4.5 and 4.8).

For patients switching from separate tablets of dapagliflozin and metformin

Patients switching from separate tablets of dapagliflozin (10 mg total daily dose) and metformin to Xigduo should receive the same daily dose of dapagliflozin and metformin already being taken or the nearest therapeutically appropriate dose of metformin.

Special populations

Renal impairment

A GFR should be assessed before initiation of treatment with metformin containing medicinal 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 Xigduo is available, individual mono-components 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, 4.4 and 5.2).

Elderly (≥65 years)

Because metformin is eliminated in part by the kidney, and because elderly patients are more likely to have decreased renal function, this medicinal product 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 elderly patients (see sections 4.3 and 4.4). Risk of volume depletion with dapagliflozin should also be taken into account (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Xigduo in children and adolescents aged 0 to <18 years have not yet been established. No data are available.

Method of administration

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

Removal of dapagliflozin by haemodialysis has not been studied. The most effective method to remove metformin and lactate is haemodialysis.

Dapagliflozin

Dapagliflozin did not show any toxicity in healthy subjects at single oral doses up to 500 mg (50 times the maximum recommended human dose). These subjects had detectable glucose in the urine for a dose-related period of time (at least 5 days for the 500 mg dose), with no reports of dehydration, hypotension or electrolyte imbalance, and with no clinically meaningful effect on QTc interval. The incidence of hypoglycaemia was similar to placebo. In clinical studies where once daily doses of up to 100 mg (10 times the maximum recommended human dose) were administered for 2 weeks in healthy subjects and type 2 diabetes subjects, the incidence of hypoglycaemia was slightly higher than placebo and was not dose-related. Rates of adverse events including dehydration or hypotension were similar to placebo, and there were no clinically meaningful dose-related changes in laboratory parameters, including serum electrolytes and biomarkers of renal function.

In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status.

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.

3 years.

This medicinal product does not require any special storage conditions.

PVC/PCTFE/Alu blister.

Pack sizes:

14, 28, 56 and 60 film-coated tablets in non-perforated blisters.

60 × 1 film-coated tablets in perforated unit dose blisters.

Multipack containing 196 (2 packs of 98) film-coated tablets in non-perforated blisters.

Not all pack sizes may be marketed.

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