XIGDUO XR

What it is

XIGDUO XR contains two oral antihyperglycaemic drugs used in the management of type 2 diabetes: dapagliflozin propanediol monohydrate and metformin hydrochloride. XIGDUO XR is available as modified release tablets in three strengths: 10 mg dapagliflozin with 500 mg metformin hydrochloride, 10 mg dapagliflozin with 1000 mg metformin hydrochloride, and 5 mg dapagliflozin with 1000 mg metformin hydrochloride.

Approved indications

— Glycaemic control in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control when treatment with both dapagliflozin and metformin is appropriate. — Prevention of hospitalisation for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease or risk factors for cardiovascular disease to reduce the risk of hospitalisation for heart failure.

Dosing overview

The dosage of antihyperglycaemic therapy with XIGDUO XR should be individualised on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended dose of dapagliflozin 10 mg and metformin extended-release 2000 mg. XIGDUO XR should generally be administered once daily with the evening meal. The recommended dose of dapagliflozin is 10 mg once daily. The recommended starting dose of metformin extended-release is 500 mg once daily, which can be titrated to 2000 mg once daily.

Key safety warnings

Life-threatening lactic acidosis can occur due to accumulation of metformin, with the main risk factor being renal impairment and other risk factors including old age associated with reduced renal function and high doses of metformin above 2 g per day. Lactic acidosis is a very rare but serious and potentially fatal metabolic complication that can occur due to metformin accumulation, with reported cases primarily occurring in patients with diabetes with significant renal failure. There have been reports of ketoacidosis, including diabetic ketoacidosis, a serious life-threatening condition requiring urgent hospitalisation in patients taking dapagliflozin and other SGLT2 inhibitors, and fatal cases of ketoacidosis have been reported in patients taking dapagliflozin. Patients treated with XIGDUO XR who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath, should be assessed for ketoacidosis, even if blood glucose levels are below 14 mmol/L. There have been postmarketing reports of acute kidney injury, some requiring hospitalisation and dialysis, in patients receiving SGLT2 inhibitors, including dapagliflozin; some reports involved patients younger than 65 years of age. There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalisation in patients receiving sodium-glucose cotransporter 2 inhibitors, including dapagliflozin. Postmarketing cases of necrotising fasciitis of the perineum (also known as Fournier's gangrene), a rare but serious and potentially life-threatening necrotising infection, have been reported in female and male patients with diabetes mellitus treated with SGLT2 inhibitors, including dapagliflozin, with serious outcomes including hospitalisation, multiple surgeries, and death. The diuretic effect of dapagliflozin is a potential concern for volume depleted patients, as dapagliflozin induces osmotic diuresis which may lead to modest decrease in blood pressure.

Contraindications

XIGDUO XR is contraindicated in patients with a history of serious hypersensitivity reaction to the active substance or to any of the excipients, metabolic acidosis (acute or chronic, including lactic acidosis or diabetic ketoacidosis, with or without coma), diabetic pre-coma, eGFR persistently less than 45 mL/min/1.73m², acute conditions with the potential to alter renal function such as dehydration, severe infection, shock, or intravascular administration of iodinated contrast agents, 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, or pancreatitis, during or immediately following surgery where insulin is essential or elective major surgery, hepatic impairment, acute alcohol intoxication, or alcoholism, and lactation.

PBS listing

No source document contains information about the PBS listing for XIGDUO XR.

Regulatory history

XIGDUO XR was first listed on the ARTG on 2014-07-18 in three strengths: 5/1000, 10/1000, and 10/500 mg tablets. The TGA approved the registration of Xigduo XR tablets on 2014-07-11 for the treatment of type 2 diabetes mellitus.