Clin. Cardio\. 14 (Supp\. IV), IV-33- 37 (1991)
Safety Profile of Benazepril in Essential Hypertension MALCOLM MA CNAB . M. D .. Ph .D .. *t SUSAN MALLOwS t
*Departments of Medici ne and Pharmacology , Medical College of Pennsy lvania , Phil adelphia , Pennsylvania; t Department of Cardiovascular Drug Development , CIBA-GEIGY Corporation, Summit, New Jersey , USA
Summary: Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril -treated patients and in 18 % of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizzines ,and fatigue. The incidence of side effects was not affected by the degree of hypertension , age, gender, race , dosage, or the degree of renal impairment . Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension , which occurred at a relatively low rate with benazepril , and hyperkalemia and elevation of serum creatinine, which occun'ed to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor ide effect is unknown ; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertenive patients treated with benazepril has not been reported. Overall , benazepril is generally well tolerated by hyperten ive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.
Key words: benazepril, angiotensin-converting enzyme inhibitors , hyperten sion safety profile
Addre s for reprints : Malcolm MacNab, M.D., Ph .D. ardiovascu lar Drug Development elBA-GEIGY Phamluceutica ls 556 Morris Avenue Summit, NJ 0790 I, USA
Introduction As a class, the angiotensin-converting enzyme (ACE) inhibitor drugs used in the treatment of hypertension are characterized by a favorable safety profile. Several new compounds are under development , including benazepril, a prodrug that is hydrolyzed following oral admini tration to benazeprilat , a highly active ACE inhibitor. Preliminary investigations with this drug have shown that the safety profile of benazepril i similar to that of other ACE inhibitors . To date, approximately 100 clinical trials have been conducted , involving nearly 6 ,000 subjects or patients with hypertension or congestive heart failure. Of these, approximately 700 patient have been followed for I year and a slightly smaller number for 2 years . The studies have included double-blind placebo-controll ed and active-controlled trials, double-blind trials with other ACE inhibitors , and open-label trials . The afety data de cribed in this report are derived primarily from the controlled trials submitted in the Benazepril New Drug Application (NDA) for hypertension.
Overall Safety and Tolerability of Benazepril As of November 1988 , the total number of hypertensive patients included in the analysis of the controlled tri als was 1693 patients receiving benazepril and 458 receiving placebo . Patients in the e trial s had mild to moderate hypertension . The overall incidence of ide effects considered to be treatment related wa 20% in the benazepriltreated group and 18 % in the placebo group (Table I). Discontinuation of therapy because of adverse experiences :-vas required !n 4 % of patient treated with benazepril and In 3 % of patrents who received placebo. The incidence of each specific adverse experience also wa approximately equal in the benazepri l and placebo group . Headache dizziness, and fatigue were the mo t commonly reported side effects with benazepril .
Safety in Special Populations The comparative incidence of ide effect b tween the benazepril and placebo groups remained con i tCnt in sub-
Clin. Cardiol. Vol. 14 (Suppl. IV), August 1991
IV-34
group analyses according to degree of hypertension, age, race, gender, dosage, and ptesence of renal impairment. The lack of an increase in side effects in patients 65 years of age and older is a distinguishing feature of the toLerability of benazepril. The incidence of side effects in this age group was actually lower than in younger patients (Table II).
TABLE I Most frequent drug-related adverse experiences reported in controlled trials of benazepril Percent of patients Benazepril (n= 1693)
Placebo (n=458)
20 5 3 3 2 2
18 5 3 3
Total Headache Dizziness Fatigue Increased cough Nausea Postural dizziness Somnolence Vertigo
Safety Profile of Benazepril in Essential Hypertension MALCOLM MA CNAB . M. D .. Ph .D .. *t SUSAN MALLOwS t
*Departments of Medici ne and Pharmacology , Medical College of Pennsy lvania , Phil adelphia , Pennsylvania; t Department of Cardiovascular Drug Development , CIBA-GEIGY Corporation, Summit, New Jersey , USA
Summary: Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril -treated patients and in 18 % of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizzines ,and fatigue. The incidence of side effects was not affected by the degree of hypertension , age, gender, race , dosage, or the degree of renal impairment . Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension , which occurred at a relatively low rate with benazepril , and hyperkalemia and elevation of serum creatinine, which occun'ed to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor ide effect is unknown ; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertenive patients treated with benazepril has not been reported. Overall , benazepril is generally well tolerated by hyperten ive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.
Key words: benazepril, angiotensin-converting enzyme inhibitors , hyperten sion safety profile
Addre s for reprints : Malcolm MacNab, M.D., Ph .D. ardiovascu lar Drug Development elBA-GEIGY Phamluceutica ls 556 Morris Avenue Summit, NJ 0790 I, USA
Introduction As a class, the angiotensin-converting enzyme (ACE) inhibitor drugs used in the treatment of hypertension are characterized by a favorable safety profile. Several new compounds are under development , including benazepril, a prodrug that is hydrolyzed following oral admini tration to benazeprilat , a highly active ACE inhibitor. Preliminary investigations with this drug have shown that the safety profile of benazepril i similar to that of other ACE inhibitors . To date, approximately 100 clinical trials have been conducted , involving nearly 6 ,000 subjects or patients with hypertension or congestive heart failure. Of these, approximately 700 patient have been followed for I year and a slightly smaller number for 2 years . The studies have included double-blind placebo-controll ed and active-controlled trials, double-blind trials with other ACE inhibitors , and open-label trials . The afety data de cribed in this report are derived primarily from the controlled trials submitted in the Benazepril New Drug Application (NDA) for hypertension.
Overall Safety and Tolerability of Benazepril As of November 1988 , the total number of hypertensive patients included in the analysis of the controlled tri als was 1693 patients receiving benazepril and 458 receiving placebo . Patients in the e trial s had mild to moderate hypertension . The overall incidence of ide effects considered to be treatment related wa 20% in the benazepriltreated group and 18 % in the placebo group (Table I). Discontinuation of therapy because of adverse experiences :-vas required !n 4 % of patient treated with benazepril and In 3 % of patrents who received placebo. The incidence of each specific adverse experience also wa approximately equal in the benazepri l and placebo group . Headache dizziness, and fatigue were the mo t commonly reported side effects with benazepril .
Safety in Special Populations The comparative incidence of ide effect b tween the benazepril and placebo groups remained con i tCnt in sub-
Clin. Cardiol. Vol. 14 (Suppl. IV), August 1991
IV-34
group analyses according to degree of hypertension, age, race, gender, dosage, and ptesence of renal impairment. The lack of an increase in side effects in patients 65 years of age and older is a distinguishing feature of the toLerability of benazepril. The incidence of side effects in this age group was actually lower than in younger patients (Table II).
TABLE I Most frequent drug-related adverse experiences reported in controlled trials of benazepril Percent of patients Benazepril (n= 1693)
Placebo (n=458)
20 5 3 3 2 2
18 5 3 3
Total Headache Dizziness Fatigue Increased cough Nausea Postural dizziness Somnolence Vertigo
