VELMETIA

What it is

VELMETIA is a registered Australian medicine containing sitagliptin and metformin hydrochloride. Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose, and does not stimulate insulin secretion and therefore does not cause hypoglycaemia.

Approved indications

— Type 2 diabetes mellitus in adults, children from 10 years of age and adolescents, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycaemic control.

Dosing overview

Tablets should be taken in divided doses with meals. Initially 500 mg should be taken once or twice a day and if necessary increased over a few weeks up to 1 g three times per day, with the dose titrated with gradual dose increments until the desired effect is obtained; 500 mg three times a day is often sufficient to obtain diabetic control, and if necessary the dose can be increased to 1 g three times daily, which is the maximum recommended daily dose. In children from 10 years of age and adolescents, the usual starting dose is one tablet of 500 mg or 850 mg once daily given during meals or after meals, with a maximum recommended dose of metformin of 2 g daily, taken as two or three divided doses.

Key safety warnings

Life threatening lactic acidosis can occur due to accumulation of metformin, with risk factors including renal impairment, old age and the use of high doses of metformin above 2 g per day. Lactic acidosis is a rare but serious metabolic complication that can occur due to metformin accumulation, and reported cases in patients on metformin have occurred primarily in diabetic patients with significant renal failure. The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders such as abdominal pain and severe asthenia, and lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Metformin induces a reduction in thyrotropin levels in patients with treated or untreated hypothyroidism, and regular monitoring of TSH levels is recommended in patients with hypothyroidism. In patients with known mitochondrial diseases such as Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-like episodes syndrome and Maternal inherited diabetes and deafness, metformin is not recommended due to the risk of lactic acidosis exacerbation and neurologic complications which may lead to worsening of the disease. Gastrointestinal disorders such as diarrhoea, nausea, vomiting, abdominal pain and loss of appetite are very common, occur most frequently during initiation of therapy and resolve spontaneously in most cases; to prevent them metformin should be taken in 2 or 3 daily doses during or after meals, and a slow increase of the dose may improve gastrointestinal tolerability. It is recommended that vitamin B12 serum levels are monitored annually, and the risk of low vitamin B12 levels increases with increasing metformin dose, treatment duration, and/or in patients with risk factors known to cause vitamin B12 deficiency.

Contraindications

Metformin is contraindicated in juvenile diabetes mellitus that is uncomplicated and well regulated on insulin, diabetes mellitus regulated by diet alone, during or immediately following surgery where insulin is essential, any type of metabolic acidosis such as lactic acidosis and diabetic ketoacidosis, hypersensitivity to metformin hydrochloride or to any of the excipients, diabetic pre-coma, renal failure or renal dysfunction with creatinine clearance below 60 mL/min, acute conditions with the potential to alter renal function such as dehydration, severe infection and shock, intravascular administration of iodinated contrast materials, acute or chronic disease which may cause tissue hypoxia such as cardiac failure, recent myocardial infarction, respiratory failure, pulmonary embolism, shock, acute significant blood loss, sepsis, gangrene and pancreatitis, elective major surgery, severe hepatic insufficiency, acute alcohol intoxication and alcoholism. Metformin is also contraindicated during lactation.

Regulatory history

VELMETIA was first listed on the ARTG on 19 November 2014.