Benazepril hydrochloride and hydrochlorothiazide has been evaluated for safety in over 2500 patients with hypertension; over 500 of these patients were treated for at least 6 months, and over 200 were treated for more than 1 year. The reported side effects were generally mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects was required in approximately 7% of U.S. patients treated with benazepril hydrochloride and hydrochlorothiazide and in 4% of patients treated with placebo.
The most common reasons for discontinuation of therapy with benazepril hydrochloride and hydrochlorothiazide in U.S. studies were cough (1.0%; see PRECAUTIONS ), “dizziness” (1.0%), headache (0.6%), and fatigue (0.6%). 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 and hydrochlorothiazide are shown in the table below.
Reactions Possibly or Probably Drug Related Patients in U.S. Placebo-Controlled Studies Benazepril Hydrochloride and Hydrochlorothiazide N=665 Placebo N=235 N % N % “Dizziness” 41 6.3 8
0.4 Other side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in 0.3% to 1.0% of patients treated with benazepril hydrochloride and hydrochlorothiazide were the following: Cardiovascular Palpitations, flushing. Gastrointestinal Vomiting, diarrhea, dyspepsia, anorexia, and constipation. Neurologic and Psychiatric Insomnia, nervousness, paresthesia, libido decrease, dry mouth, taste perversion, and tinnitus.
Dermatologic Rash and sweating. Other Urinary frequency, arthralgia, myalgia, asthenia, and pain (including chest pain and abdominal pain). Other adverse experiences reported in 0.3% or more of benazepril hydrochloride and hydrochlorothiazide patients in U.S. controlled clinical trials, and rarer events seen in post-marketing experience, were the following; asterisked entries occurred in more than 1% of patients (in some, a causal relationship to benazepril hydrochloride and hydrochlorothiazide is uncertain): Cardiovascular Syncope, peripheral vascular disorder, and tachycardia.
Body as a Whole Infection, back pain*, flu syndrome*, fever, chills, and neck pain. Dermatologic Photosensitivity and pruritus. Gastrointestinal Gastroenteritis, flatulence, and tooth disorder. Neurologic and Psychiatric Hypesthesia, abnormal vision, abnormal dreams, and retinal disorder. Respiratory Upper respiratory infection*, epistaxis, bronchitis, rhinitis*, sinusitis*, and voice alteration. Other Conjunctivitis, arthritis, urinary tract infection, alopecia, and urinary frequency*.
Post-Marketing Experience The following adverse reactions have been identified during post-approval use of either benazepril or hydrochlorothiazide. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure: Non-melanoma Skin Cancer Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer.
In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.
Benazepril Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphigus, and thrombocytopenia, eosinophilic pneumonitis. Hydrochlorothiazide Digestive Pancreatitis, small bowel angioedema, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia. Neurologic Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.
Musculoskeletal Muscle spasm. Hematologic Aplastic anemia, agranulocytosis, leukopenia, neutropenia and thrombocytopenia. Metabolic Hyperglycemia, glycosuria, and hyperuricemia, pyrexia, asthenia, parathyroid gland changes with hypercalcemia and hypophosphatemia. Hypersensitivity Anaphylactoid reactions, necrotizing angiitis, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity.
Skin Erythema multiforme including Stevens-Johnson syndrome, and exfoliative dermatitis including toxic epidermal necrolysis. Clinical Laboratory Test Findings Serum Electrolytes See PRECAUTIONS . Creatinine and BUN Minor reversible increases in serum creatinine and BUN were observed in patients with essential hypertension treated with benazepril hydrochloride and hydrochlorothiazide. Such increases occurred most frequently in patients with renal artery stenosis (see PRECAUTIONS ).
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
