The Safety and Tolerability of Lisinopril in Clinical Trials

The safety and tolerability of lisinopril were assessed in 1,476 patients [1,165 hypertensives and 311 patients with congestive heart failure (CHF)| and 211 normal volunteers. The duration of lisinopril therapy ranged from 1 day to 16 months, with a mean duration of 105 days. In the hypertensive population, the most frequent clinical adverse experiences on lisinopril alone were headache, dizziness, cough, and diarrhea. Not all of these adverse experiences were thought to be drug related. Five percent of patients were discontinued because of adverse clinical experiences; cough and dizziness were the most common reasons for discontinuation. Two of 1.165 (0.179f) hypertensive patients treated with lisinopril died, compared to 0.419f of hypertensive patients on other therapies. Neither case was considered to be drug related. In patients with CHF, the most frequent clinical adverse experiences were dizziness, diarrhea, hypotension. fatigue, headache, and rash. Not all of these adverse experiences were thought to be drug related. The percent of CHF patients discontinuing because of an adverse clinical experience was 7.4%; the most frequent causes for discontinuation were hypotension, dizziness, or renal impairment. Twelve deaths occurred in 311 CHF patients treated with lisinopril (3.9%) compared to 4/104 (3.8%) of CHF patients treated with placebo and 2/65 (3.1%) treated with captopril. Hypotension, orthostatic effects, or dizziness following the initial lisinopril dose occurred infrequently in patients treated with lisinopril. In hypertensive patients with normal renal function, including those treated previously or concomitantly with diuretic therapy, a first-dose hypotensive episode was reported in six of 955, or 0.6%. The incidence was higher (6.7%) in hypertensive patients with impaired renal function. Eleven (4%) of 248 CHF patients with normal renal function reported first-dose hypotension or symptoms suggesting hypotension; all of these patients were receiving one or more diuretics concomitantly. In CHF patients with renal impairment, no instances of first-dose hypotension were reported, although experience in this patient population is limited. Changes in laboratory values in lisinopril-treated patients were generally minor and seldom resulted in discontinuation of therapy. In conclusion, lisinopril was generally well tolerated. Adverse experiences were usually of mild to moderate intensity and usually did not require discontinuation of therapy.