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.
4 mg, 8 mg and 16 mg tablets
Approved indication: hypertension
AMH Section 6.4.5
Two AT1 receptor antagonists (losartan and irbesartan) are already available in Australia.1 Candesartan adds to the choices for treating mild to moderate hypertension.
The tablets contain a prodrug which is rapidly converted to active candesartan during absorption. Peak serum concentrations are reached within 4 hours. Food increases the rate of absorption, but does not affect the bioavailability which is approximately 14%. Most of a dose is excreted in the urine, so a lower starting dose is recommended for the elderly and patients with severe renal impairment. The terminal half-life is approximately 9 hours. Although the effect on blood pressure peaks a few hours after a dose, its duration permits once daily dosing.
Candesartan reduces blood pressure more than placebo. The maximum effect on blood pressure is reached within one month. This effect is comparable to the effects of hydrochlorothiazide, amlodipine or enalapril. A dose of 16 mg candesartan may cause a greater reduction in diastolic blood pressure than 50 mg losartan. In common with other AT1 receptor antagonists, few patients (2.4%)had to withdraw from clinical trials because of adverse effects. A study of candesartan in heart failure was halted because of concerns about increased mortality. While the significance of this observation is unclear, the drug is not recommended for patients with heart failure. It should not be used inpatients with renal artery stenosis and should be used with caution in patients who are salt or volume depleted.