Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Rezulin (Parke Davis)
200 mg and 400 mg tablets
Approved indication: type 2 diabetes
Australian Medicines Handbook Section 10.1
The drug treatment of non-insulin dependent diabetes aims at increasing insulin secretion or making the peripheral cells more sensitive to insulin.1 Although it has a different action to metformin, troglitazone also improves the cellular response to insulin.
In a placebo-controlled trial, six months treatment with troglitazone produced significant decreases in postprandial and fasting blood glucose concentrations.2 Adding troglitazone to treatment with a sulfonylurea, such as glibenclamide, can improve glycaemic control. Patients with type 2 diabetes who eventually require insulin may also benefit from the addition of troglitazone. In placebo-controlled studies, some patients taking troglitazone and insulin have been able to reduce their dose of insulin. There were improvements in the concentrations of blood glucose and HbA1c.
Troglitazone is taken once a day. Its absorption is increased by food so it should be taken with a meal. Troglitazone is completely metabolised with most of the metabolites being excreted in the faeces. An interaction with terfenadine and oral contraceptives suggests that troglitazone may induce CYP3A4. This raises the possibility of an interaction with other drugs metabolised by the enzyme e.g. triazolam, calcium channel blockers, HMG CoA reductase inhibitors and corticosteroids. There are no pharmacokinetic effects on digoxin or warfarin.
The drug is contraindicated in liver disease, but all patients should have their liver palpated and their liver function tests checked regularly. This is because severe idiosyncratic liver damage can occur. Although this is usually reversible, it has resulted in liver transplant or death on rare occasions. Concern about these hepatic adverse effects led to the withdrawal of troglitazone in the U.K. Troglitazone should therefore be used with extreme caution if prescribed with other drugs that can alter liver function e.g. HMG CoA reductase inhibitors.
Although troglitazone can be used in the U.S.A. with oral hypoglycaemic agents, its use in Australia will be more restricted. In Australia, the drug is only approved for patients with type 2 diabetes who require insulin. Troglitazone should only be considered if the patient's blood glucose is not controlled by insulin.
