Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors.

OBJECTIVE

To examine the safety profile and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II type 1 (AT1) receptor.

METHODS

Approximately 2000 hypertensive patients were treated in double-blind clinical trials with losartan, placebo or other antihypertensive drug classes.

RESULTS

Headache (14.1%), upper respiratory infection (6.5%), dizziness (4.1%), asthenia/fatigue (3.8%) and coughing (3.1%) were the most commonly reported clinical adverse experiences in patients treated with losartan. These adverse experiences were also commonly reported in patients treated with a placebo: 17.2, 5.6, 2.4, 3.9 and 2.6%, respectively. A dry cough was reported by 8.8% of patients treated with angiotensin converting enzyme (ACE) inhibitors, statistically greater than that reported in patients treated with losartan and placebo, 3.1 and 2.6%, respectively (P < 0.001, losartan versus ACE inhibitors). Only dizziness was more often considered drug-related in losartan-treated patients (2.4%) than in patients who received placebo (1.3%). In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. The rate of withdrawal due to clinical adverse experiences in patients treated with losartan was 2.3% compared to 3.7% in patients treated with a placebo. No adverse laboratory results were unexpected or of clinical importance. First-dose hypotension occurred rarely with losartan, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles for the demographic subgroups of age, sex or race.

CONCLUSIONS

In controlled clinical trials losartan has demonstrated an excellent tolerability profile.