Benazepril side effects

Benazepril hydrochloride tablets have been evaluated for safety in over 6000 patients with hypertension; over 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was comparable in Benazepril hydrochloride tablets and placebo patients.

The reported side effects were generally mild and transient, and there was no relation between side effects and age, duration of therapy, or total dosage within the range of 2 to 80 mg. Discontinuation of therapy because of a side effect was required in approximately 5% of U.S. patients treated with Benazepril hydrochloride tablets and in 3% of patients treated with placebo.

The most common reasons for discontinuation were headache (0.6%) and cough (0.5%).

The side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Benazepril hydrochloride tablets are shown below;

List of side effects
Cardiovascular Renal Fetal/Neonatal Morbidity and Mortality Angioedema Dermatologic Gastrointestinal Hematologic Neurologic and Psychiatric Other Pediatric Patients Clinical Laboratory Test Findings

Cardiovascular
Symptomatic hypotension was seen in 0.3% of patients, postural hypotension in 0.4%, and syncope in 0.1%; these reactions led to discontinuation of therapy in 4 patients who had received Benazepril monotherapy and in 9 patients who had received Benazepril with hydrochlorothiazide. Other reports included angina pectoris, palpitations, and peripheral edema.

Return to top

Renal
Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving Benazepril hydrochloride tablets, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine.

Return to top

Fetal/Neonatal Morbidity and Mortality
ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.

The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE inhibitor exposure.

These adverse effects do not appear to have resulted from intrauterine ACE inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of Benazepril as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.

If oligohydramnios is observed, Benazepril should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a nonstress test (NST), or biophysical profiling ( BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. Benazepril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means; there are occasional reports of benefit from these maneuvers with another ACE inhibitor, but experience is limited.

No teratogenic effects of Benazepril hydrochloride were seen in studies of pregnant rats, mice, and rabbits. On a mg/m2 basis, the doses used in these studies were 60 times (in rats), 9 times (in mice), and more than 0.8 times (in rabbits) the maximum recommended human dose (assuming a 50-kg woman). On a mg/kg basis these multiples are 300 times (in rats), 90 times (in mice), and more than 3 times (in rabbits) the maximum recommended human dose.

Return to top

Angioedema
Angioedema has been reported in patients receiving ACE inhibitors. During clinical trials in hypertensive patients with Benazepril, 0.5% of patients experienced edema of the lips or face without other manifestations of angioedema. Angioedema associated with laryngeal edema and/or shock may be fatal. If angioedema of the face, extremities, lips, tongue, or glottis and/or larynx occurs, treatment with Benazepril hydrochloride tablets should be discontinued and appropriate therapy instituted immediately.

Return to top

Dermatologic
Stevens-Johnson syndrome, pemphigus, apparent hypersensitivity reactions (manifested by dermatitis, pruritus, or rash), photosensitivity, and flushing.

Return to top

Gastrointestinal
Pancreatitis, constipation, gastritis, vomiting, and melena.

Return to top

Hematologic
Thrombocytopenia and hemolytic anemia.

Return to top

Neurologic and Psychiatric
Anxiety, decreased libido, hypertonia, insomnia, nervousness, and paresthesia.

Return to top

Other
Asthma, bronchitis, dyspnea, sinusitis, urinary tract infection, infection, arthritis, impotence, alopecia, arthralgia, myalgia, asthenia and sweating.

Another potentially important adverse experience, eosinophilic pneumonitis, has been attributed to other ACE inhibitors.

Return to top

Pediatric Patients
The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients. Infants below the age of 1 year should not be given ACE inhibitors due to concerns over possible effects on kidney development.

The long-term effects of Benazepril on growth and development have not been studied.

Return to top

Creatinine and Blood Urea Nitrogen
Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving Benazepril hydrochloride tablets, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine. None of these increases required discontinuation of treatment. Increases in these laboratory values are more likely to occur in patients with renal insufficiency or those pretreated with a diuretic and, based on experience with other ACE inhibitors, would be expected to be especially likely in patients with renal artery stenosis.

Return to top

Potassium
Since Benazepril decreases aldosterone secretion, elevation of serum potassium can occur. Potassium supplements and potassium-sparing diuretics should be given with caution, and the patient's serum potassium should be monitored frequently

Return to top

Hemoglobin
Decreases in hemoglobin (a low value and a decrease of 5 g/dL) were rare, occurring in only 1 of 2014 patients receiving Benazepril hydrochloride tablets alone and in 1 of 1357 patients receiving Benazepril hydrochloride tablets plus a diuretic. No U.S. patients discontinued treatment because of decreases in hemoglobin.

Return to top

Other (causal relationships unknown)
Clinically important changes in standard laboratory tests were rarely associated with Benazepril hydrochloride administration.

Elevations of uric acid, blood glucose, serum bilirubin, and liver enzymes have been reported, as have scattered incidents of hyponatremia, electrocardiographic changes, leukopenia, eosinophilia, and proteinuria. In U.S. trials, less than 0.5% of patients discontinued treatment because of laboratory abnormalities.

Return to top