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.
Cozaar (Merck Sharp & Dohme)
50 mg tablets
The renin-angiotensin system (RAS) is involved in the control of blood pressure. In patients with hypertension, ACE inhibitors block the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. Losartan also affects the RAS, but reduces blood pressure by antagonising angiotensin II at its receptor.
The drug is well absorbed, but the bioavailability is only33% as it undergoes first pass metabolism. While the peak plasma concentration of losartan is reached after one hour, the active metabolite peaks at 4 hours. The drug has a half-life of two hours and the metabolite has a half-life of6-9 hours. Only 4% of a dose is excreted unchanged in the urine.
The usual starting dose is 50 mg once a day. Although symptomatic hypotension can occur early, particularly in volume-depleted patients, the maximal antihypertensive effect occurs up to 6 weeks after starting treatment. If 50 mg a day does not control the blood pressure, the manufacturers suggest giving 25 mg twice a day before increasing the dose. Increasing the dose may not produce much change in blood pressure and the maximum dose should not exceed100 mg a day.
The company claims that the drug has a similar efficacy to daily doses of enalapril 20 mg, atenolol 50 mg and felodipine 5 mg. The long-term effectiveness of losartan is unknown.
Like ACE inhibitors, losartan is contraindicated in pregnancy. As the clinical studies of losartan have been relatively short, there are no data on how safe the drug will be if it is taken for several years. In the clinical trials, dizziness was the only symptom that occurred much more frequently with losartan than with placebo (4.1% vs. 2.4%). Hyperkalaemia can occur and serum concentrations of uric acid are reduced.
Losartan is not more effective than ACE inhibitors, but it causes less cough. As mild to moderate hypertension usually requires long-term treatment, this drug will have a limited role until more data become available.