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.
Karvea (Sanofi Winthrop)
Avapro ( Bristol-Myers Squibb)
75 mg, 150 mg and 300 mg tablets
Indication: hypertension
Irbesartan is the second angiotensin II receptor antagonist to be registered. (Losartan is already available in Australia.) Blocking the AT1 receptor stops the vasoconstrictive effects of angiotensin.
The usual dose of irbesartan is 150 mg daily. This is reduced if the patient is volume- or salt-depleted e.g. after treatment with diuretics. The tablets have a bioavailability of 60-80% which is unaffected by food. Most of the drug is metabolised by the liver. It has a half-life of 11-15 hours with the metabolites being excreted in faeces and urine.
Clinical trials have compared irbesartan with placebo and found it to have a greater antihypertensive effect. This effect appears within two weeks of starting treatment and peaks within 6 weeks. The mean decreases in systolic/diastolic blood pressure after 6-12 weeks' treatment with 150 mg irbesartan are approximately 7.5-10/4.5-6 mmHg. When the response is inadequate, the dose can be increased to 300 mg once daily. If the blood pressure is still not controlled by this dose, then hydrochlorothiazide can be added.
In clinical trials, 3.3% of the patients taking irbesartan withdrew because of adverse events. More patients withdrew from the placebo group. While headaches, fatigue and muscle pain may be reported, their frequency is not significantly greater than placebo. Cough occurred in 2.8% of the patients taking irbesartan and 2.7% of the placebo group. As sudden deaths have been reported, extra caution is needed when prescribing irbesartan for hypertensive patients who also have heart failure or a history of arrhythmia. Patients with heart failure or impaired renal function should have their serum potassium measured during treatment with irbesartan.
Irbesartan is probably as effective as an ACE inhibitor at lowering the blood pressure; however, there are no data on its long-term effects. Until more data are available, irbesartan will probably be reserved for use in patients who cannot take an ACE inhibitor.
