Benazepril Hydrochloride (Page 4 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was found when benazepril was administered to rats and mice for up to two years at doses of up to 150 mg/kg/day. When compared on the basis of body weights, this dose is 110 times the maximum recommended human dose. When compared on the basis of body surface areas, this dose is 18 and 9 times (rats and mice, respectively) the maximum recommended human dose (calculations assume a patient weight of 60 kg). No mutagenic activity was detected in the Ames test in bacteria (with or without metabolic activation), in an in vitro test for forward mutations in cultured mammalian cells, or in a nucleus anomaly test. In doses of 50 to 500 mg/kg/day (6 to 60 times the maximum recommended human dose based on mg/m2 comparison and 37 to 375 times the maximum recommended human dose based on a mg/kg comparison), benazepril had no adverse effect on the reproductive performance of male and female rats.

14 CLINICAL STUDIES

Hypertension

Adult Patients

In single-dose studies, benazepril lowered blood pressure within 1 hour, with peak reductions achieved between 2 and 4 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. In multiple-dose studies, once-daily doses of between 20 mg and 80 mg decreased seated pressure 24 hours after dosing by about 6 to 12 mm Hg systolic and 4 to 7 mm Hg diastolic. The trough values represent reductions of about 50% of that seen at peak.

Four dose-response studies using once-daily dosing were conducted in 470 mild-to-moderate hypertensive patients not using diuretics. The minimal effective once-daily dose of benazepril was 10 mg; but further falls in blood pressure, especially at morning trough, were seen with higher doses in the studied dosing range (10 to 80 mg). In studies comparing the same daily dose of benazepril given as a single morning dose or as a twice-daily dose, blood pressure reductions at the time of morning trough blood levels were greater with the divided regimen.

The antihypertensive effects of benazepril were not appreciably different in patients receiving high- or low-sodium diets.

In normal human volunteers, single doses of benazepril caused an increase in renal blood flow but had no effect on glomerular filtration rate.

Use of benazepril in combination with thiazide diuretics gives a blood-pressure-lowering effect greater than that seen with either agent alone. By blocking the renin-angiotensin-aldosterone axis, administration of benazepril tends to reduce the potassium loss associated with the diuretic.

Pediatric Patients

In a clinical study of 107 pediatric patients, 7 to 16 years of age, with either systolic or diastolic pressure above the 95th percentile, patients were given 0.1 or 0.2 mg/kg then titrated up to 0.3 or 0.6 mg/kg with a maximum dose of 40 mg once daily. After four weeks of treatment, the 85 patients whose blood pressure was reduced on therapy were then randomized to either placebo or benazepril and were followed up for an additional two weeks. At the end of two weeks, blood pressure (both systolic and diastolic) in children withdrawn to placebo rose by 4 to 6 mm Hg more than in children on benazepril. No dose-response was observed.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 50090-5751

NDC: 50090-5751-0 30 TABLET, FILM COATED in a BOTTLE

NDC: 50090-5751-2 90 TABLET, FILM COATED in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Pregnancy: Tell female patients of childbearing age about the consequences of exposure to benazepril during pregnancy. Discuss treatment options with women planning to become pregnant. Instruct patients to report pregnancies to their physicians as soon as possible.

Angioedema: Angioedema, including laryngeal edema, can occur at any time with treatment with ACE inhibitors. Tell patients to report immediately any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to take no more drugs until they have consulted with the prescribing physician.

Symptomatic Hypotension: Tell patients to report light-headedness especially during the first few days of therapy. If actual syncope occurs, tell the patients to discontinue the drug until they have consulted with the prescribing physician.

Tell patients that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of a reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; advise patients accordingly.

Hyperkalemia: Tell patients not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.

Hypoglycemia: Tell diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor to monitor for hypoglycemia closely, especially during the first month of combined use.

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 038, India Revised: 02/2019

BENAZEPRIL HYDROCHLORIDE

Label ImageLabel Image
BENAZEPRIL HYDROCHLORIDE benazepril hydrochloride tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-5751(NDC:65862-116)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BENAZEPRIL HYDROCHLORIDE (BENAZEPRILAT) BENAZEPRIL HYDROCHLORIDE 10 mg
Inactive Ingredients
Ingredient Name Strength
MICROCRYSTALLINE CELLULOSE
LACTOSE MONOHYDRATE
STARCH, CORN
CROSPOVIDONE (15 MPA.S AT 5%)
SILICON DIOXIDE
MAGNESIUM STEARATE
HYPROMELLOSE 2910 (3 MPA.S)
HYPROMELLOSE 2910 (6 MPA.S)
TITANIUM DIOXIDE
POLYETHYLENE GLYCOL 400
POLYSORBATE 80
FERRIC OXIDE YELLOW
Product Characteristics
Color YELLOW (Dark Yellow) Score no score
Shape ROUND (Biconvex, Beveled Edge) Size 8mm
Flavor Imprint Code E;15
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:50090-5751-0 30 TABLET, FILM COATED in 1 BOTTLE None
2 NDC:50090-5751-2 90 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078212 05/22/2008
Labeler — A-S Medication Solutions (830016429)
Establishment
Name Address ID/FEI Operations
A-S Medication Solutions 830016429 RELABEL (50090-5751), REPACK (50090-5751)

Revised: 10/2021 A-S Medication Solutions

Page 4 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.