Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension.
This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered "drug-related" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. 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. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, 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 in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.
Goldberg
A I
AI
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Dunlay
M C
MC
Sweet
C S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D001262:Atenolol / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D003371:Cough / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D015736:Felodipine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012141:Respiratory Tract Infections / Q000139:chemically induced; D012449:Safety; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D010919:Placebos; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D001262:Atenolol; D019808:Losartan; D015736:Felodipine