ACTOS

What it is

ACTOS contains pioglitazone hydrochloride and is available in tablet strengths of 15 mg, 30 mg or 45 mg. 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.

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

ACTOS should be taken once daily with or without food. Dosing varies according to treatment approach.

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

Key safety warnings

Pioglitazone can cause or exacerbate congestive heart failure in some patients. In post-marketing experience with pioglitazone, congestive heart failure has been reported in patients both with and without pre-existing cardiac disease. After initiation of pioglitazone and after dose increases, patients should be observed carefully for signs and symptoms of heart failure including excessive, rapid weight gain, dyspnoea and/or oedema. 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. Patients should be advised to promptly seek the attention of their physician if macroscopic haematuria or other symptoms such as urinary urgency develop during treatment. An increased incidence in bone fractures in women was seen in a pooled analysis of adverse event reports from randomised, controlled, double-blind clinical trials. Fractures were observed in 2.6% of women taking pioglitazone compared to 1.7% of women treated with a comparator.

Contraindications

ACTOS 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. ACTOS should not be used in type 1 diabetes or for the treatment of diabetic ketoacidosis.

PBS listing

ACTOS is listed on the PBS in strengths of 15 mg, 30 mg and 45 mg (as hydrochloride) in packs of 30 tablets with restricted authority required status. The ex-manufacturer prices are A$6.62 for 15 mg, A$10.19 for 30 mg, and A$13.25 for 45 mg.

Regulatory history

ACTOS pioglitazone hydrochloride tablets in strengths of 15 mg, 30 mg and 45 mg were first registered on the ARTG on 2001-02-06.