XIGDUO XR TABLETS 10MG/1000MG

4.1 Therapeutic indications

XIGDUO XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both dapagliflozin and metformin is appropriate.

For study results with respect to combination of therapies, effects on glycemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Limitations of Use

XIGDUO XR is not indicated for use in patients with type 1 diabetes.

XIGDUO XR should not be used for the treatment of diabetic ketoacidosis.

4.3 Contraindications

XIGDUO XR is contraindicated in patients with:

• Hypersensitivity to the active substances or to any of the excipients;
• Diabetic ketoacidosis, diabetic pre-coma;
• Severe renal impairment (eGFR < 30 mL/min/1.73 m2);
• Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock, or intravascular administration of iodinated contrast agents (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information);
• Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, pulmonary embolism, recent myocardial infarction, shock, acute significant blood loss, sepsis, gangrene, pancreatitis;
• During or immediately following surgery where insulin is essential, elective major surgery;
• Hepatic impairment;
• Acute alcohol intoxication, alcoholism;
• Lactation.

4.2 Posology and method of administration

4.2.1 Dapagliflozin/metformin HCL extended-release tablets

XIGDUO XR should be taken orally, once daily with the evening meal. The recommended dose of dapagliflozin is 10 mg once daily. The recommended starting dose of metformin is 500 mg once daily, which can be titrated to 2000 mg once daily, with gradual dose escalation to reduce the gastrointestinal side effects due to metformin. The maximum dose of XIGDUO XR is dapagliflozin 10 mg/metformin extended-release 2000 mg taken as two 5 mg/1000 mg tablets once daily.

In patients treated with metformin, the dose of XIGDUO XR should provide metformin at the dose already being taken, or the nearest therapeutically appropriate dose.

If no adequate strength of XIGDUO XR is available, individual mono-components should be used instead of the fixed dose combination.

Patients should be informed that XIGDUO XR tablets must be swallowed whole and never crushed, cut, or chewed. Occasionally, the inactive ingredients of XIGDUO XR will be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet.

4.2.2 Special populations

Patients with renal impairment

Assess renal function prior to initiation of XIGDUO XR and periodically thereafter (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Mild renal impairment

No dose adjustment of XIGDUO XR is required for patients with mild renal impairment (eGFR 60–89 mL/min/1.73 m2 by Modified Diet in Renal Disease [MDRD] eGFR equation).

Moderate renal impairment

XIGDUO XR is not recommended for the treatment of diabetes in patients with eGFR persistently below 45 mL/min/1.73 m2 (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). No dose adjustment is required for patients with eGFR ≥ 45 mL/min/1.73 m2.

Severe renal impairment

Due to the metformin component, XIGDUO XR is contraindicated in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) (see section 4.3).

Patients with hepatic impairment

Since impaired hepatic function has been associated with some cases of lactic acidosis in patients taking metformin, XIGDUO XR should generally be avoided in patients with clinical or laboratory evidence of hepatic impairment (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Pediatric and adolescent patients

Safety and effectiveness of XIGDUO XR in pediatric and adolescent patients have not been established.

Elderly patients

Because metformin is eliminated by the kidney, and because elderly patients are more likely to have decreased renal function, XIGDUO XR should be used with caution as age increases. The renal function recommendations provided for all patients also apply to elderly patients.

Patients at risk for volume depletion

For patients at risk for volume depletion due to co-existing conditions, a 5 mg starting dose of dapagliflozin may be appropriate.