VEXAZONE

What it is

VEXAZONE (pioglitazone hydrochloride) is an uncoated tablet containing 15 mg, 30 mg or 45 mg of pioglitazone as the active ingredient. Pioglitazone is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its unique mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARγ), which are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.

Approved indications

— Type 2 diabetes mellitus inadequately controlled by diet and exercise as monotherapy. — Type 2 diabetes mellitus inadequately controlled by diet and exercise as dual therapy in combination with metformin or sulfonylurea. — Type 2 diabetes mellitus inadequately controlled by diet and exercise as dual therapy in combination with insulin. — Type 2 diabetes mellitus inadequately controlled by diet and exercise as triple therapy in combination with metformin and sulfonylurea.

Dosing overview

VEXAZONE should be taken once daily with or without food. Dosing varies by therapy type.

The dose of VEXAZONE should not exceed 45 mg/day since doses higher than 45 mg/day have not been studied in clinical trials. In female patients, dosage should start at 15 mg and be increased cautiously, paying attention to the development of oedema. In patients with hepatic impairment, dosage should start at 15 mg and be increased cautiously.

Key safety warnings

Pioglitazone can cause or exacerbate congestive heart failure (CHF) in some patients. In post-marketing experience with pioglitazone, CHF has been reported in patients both with and without pre-existing cardiac disease. After initiation of pioglitazone and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnoea and/or oedema). Pioglitazone should not be prescribed to lower the risk of cardiovascular disease such as myocardial infarction and stroke or to lower cardiovascular mortality. As thiazolidinediones can cause fluid retention, pioglitazone should be used with caution in patients with oedema. In placebo-controlled clinical trials oedema was reported more frequently in patients treated with pioglitazone than in placebo-treated patients. Dose related weight gain was seen with pioglitazone alone and in combination with other hypoglycaemic agents. The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation. Pioglitazone should not be used in patients with bladder cancer or a history of bladder cancer. The risk of bladder cancer should be considered in the care of all patients treated with pioglitazone. Some epidemiological studies suggested a small increased risk of bladder cancer in diabetic patients treated with pioglitazone, although other large, long-term observational studies did not. An increased incidence of bladder cancer was observed in subjects receiving pioglitazone in the PROactive study. In the pioglitazone arm there were 14 cases (0.5%) and in the placebo arm there were 5 cases (0.2%); the point estimate for the hazard ratio was 2.7 (95% confidence interval 0.99–7.6). An increased incidence in bone fractures in women was seen in a pooled analysis of adverse event reports of bone fracture from randomised, controlled, double-blind clinical trials in over 8,100 pioglitazone and 7,400 comparator treated patients, on treatment for up to 3.5 years. Fractures were observed in 2.6% of women taking pioglitazone compared to 1.7% of women treated with a comparator. Patients receiving pioglitazone in combination with insulin or oral hypoglycaemic agents may be at risk of hypoglycaemia. A reduction in the dose of the concomitant agent may be necessary.

Contraindications

VEXAZONE is contraindicated in patients with known hypersensitivity or allergy to pioglitazone or any of the excipients. Initiation of pioglitazone is contraindicated in patients with New York Heart Association (NYHA) Class II, III or IV heart failure. VEXAZONE should not be used in type 1 diabetes or for the treatment of diabetic ketoacidosis. VEXAZONE therapy should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 times the upper limit of normal).

Regulatory history

VEXAZONE was first registered on the ARTG on 2 February 2011 across three strengths: 15 mg, 30 mg and 45 mg tablet blister packs. In May 2025, PBAC recommended VEXAZONE for the treatment of type 2 diabetes mellitus, with a new pack size and increased maximum quantity.