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/m 2 comparison and 37 to 375 times the maximum recommended human dose based on a mg/kg comparison), benazepril hydrochloride had no adverse effect on the reproductive performance of male and female rats.

14 CLINICAL STUDIES

Hypertension

Adult Patients

In single-dose studies, benazepril hydrochloride 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 mmHg systolic and 4 to 7 mmHg 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 hydrochloride 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 hydrochloride 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 hydrochloride were not appreciably different in patients receiving high- or low-sodium diets.

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

Use of benazepril hydrochloride 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 hydrochloride 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 95 th 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 mmHg more than in children on benazepril. No dose-response was observed.

16 HOW SUPPLIED/STORAGE AND HANDLING

Benazepril Hydrochloride Tablets USP, 5 mg are available as light orange, round, film-coated tablets debossed “696” on one side and plain on the other side containing 5 mg benazepril hydrochloride, packaged in bottles of 90 tablets, NDC 62135-719-90.

Benazepril Hydrochloride Tablets USP, 10 mg are available as orange, round, film-coated tablets debossed “697” on one side and plain on the other side containing 10 mg benazepril hydrochloride, packaged in bottles of 90 tablets, NDC 62135-720-90.

Benazepril Hydrochloride Tablets USP, 20 mg are available as peach, round, film-coated tablets debossed “698” on one side and plain on the other side containing 20 mg benazepril hydrochloride, packaged in bottles of 90 tablets, NDC 62135-721-90.

Benazepril Hydrochloride Tablets USP, 40 mg are available as orange-red, round, film-coated tablets debossed “699” on one side and plain on the other side containing 40 mg benazepril hydrochloride, packaged in bottles of 90 tablets, NDC 62135-722-90.

Dispense in a tight container as defined in the USP. Use child-resistant closure (as required).

Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight, light-resistant container as defined in the USP.

17 PATIENT COUNSELING INFORMATION

Pregnancy: Tell female patients of childbearing age about the consequences of exposure to benazepril hydrochloride 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.

Manufactured for:
Chartwell RX, LLC. Congers, NY 10920

Revised: 07/2023

L71621

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Benazepril Hydrochloride Tablets USP, 5 mg NDC 62135-719-90 — 90’s Bottle

Benazepril Hydrochloride Tablets USP, 5 mg NDC 62135-719-90 -- 90's Bottle
(click image for full-size original)

Benazepril Hydrochloride Tablets USP, 10 mg NDC 62135-720-90 — 90’s Bottle

Benazepril Hydrochloride Tablets USP, 5 mg NDC 62135-719-90 -- 90's Bottle
(click image for full-size original)

Benazepril Hydrochloride Tablets USP, 20 mg NDC 62135-721-90 — 90’s Bottle

Benazepril Hydrochloride Tablets USP, 5 mg NDC 62135-719-90 -- 90's Bottle
(click image for full-size original)

Benazepril Hydrochloride Tablets USP, 40 mg NDC 62135-722-90 — 90’s Bottle

Benazepril Hydrochloride Tablets USP, 5 mg NDC 62135-719-90 -- 90's Bottle
(click image for full-size original)
BENAZEPRIL HYDROCHLORIDE benazepril hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:62135-719
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BENAZEPRIL HYDROCHLORIDE (BENAZEPRILAT) BENAZEPRIL HYDROCHLORIDE 5 mg
Inactive Ingredients
Ingredient Name Strength
CROSPOVIDONE
D&C YELLOW NO. 10 ALUMINUM LAKE
FD&C YELLOW NO. 6
HYPROMELLOSE 2910 (3 MPA.S)
HYPROMELLOSE 2910 (50 MPA.S)
HYPROMELLOSE 2910 (6 MPA.S)
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
POLYDEXTROSE
POLYETHYLENE GLYCOL 400
POLYETHYLENE GLYCOL 8000
SILICON DIOXIDE
STARCH, CORN
TITANIUM DIOXIDE
TRIACETIN
Product Characteristics
Color orange (Light Orange) Score no score
Shape ROUND Size 8mm
Flavor Imprint Code 696
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:62135-719-90 90 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA076267 08/20/2022
BENAZEPRIL HYDROCHLORIDE benazepril hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:62135-720
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
CROSPOVIDONE
D&C YELLOW NO. 10 ALUMINUM LAKE
FD&C YELLOW NO. 6
HYPROMELLOSE 2910 (3 MPA.S)
HYPROMELLOSE 2910 (6 MPA.S)
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
POLYDEXTROSE
POLYETHYLENE GLYCOL 400
POLYETHYLENE GLYCOL 8000
SILICON DIOXIDE
STARCH, CORN
TITANIUM DIOXIDE
TRIACETIN
Product Characteristics
Color orange Score no score
Shape ROUND Size 8mm
Flavor Imprint Code 697
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:62135-720-90 90 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA076267 08/20/2022
BENAZEPRIL HYDROCHLORIDE benazepril hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:62135-721
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BENAZEPRIL HYDROCHLORIDE (BENAZEPRILAT) BENAZEPRIL HYDROCHLORIDE 20 mg
Inactive Ingredients
Ingredient Name Strength
CROSPOVIDONE
FD&C RED NO. 40
FD&C YELLOW NO. 6
HYPROMELLOSE 2910 (3 MPA.S)
HYPROMELLOSE 2910 (50 MPA.S)
HYPROMELLOSE 2910 (6 MPA.S)
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
POLYDEXTROSE
POLYETHYLENE GLYCOL 400
POLYETHYLENE GLYCOL 8000
SILICON DIOXIDE
STARCH, CORN
TITANIUM DIOXIDE
TRIACETIN
Product Characteristics
Color orange (Peach) Score no score
Shape ROUND Size 8mm
Flavor Imprint Code 698
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:62135-721-90 90 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA076267 08/20/2022
BENAZEPRIL HYDROCHLORIDE benazepril hydrochloride tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:62135-722
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BENAZEPRIL HYDROCHLORIDE (BENAZEPRILAT) BENAZEPRIL HYDROCHLORIDE 40 mg
Inactive Ingredients
Ingredient Name Strength
CROSPOVIDONE
FD&C RED NO. 40
FD&C YELLOW NO. 6
HYPROMELLOSE 2910 (3 MPA.S)
HYPROMELLOSE 2910 (50 MPA.S)
HYPROMELLOSE 2910 (6 MPA.S)
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
POLYDEXTROSE
POLYETHYLENE GLYCOL 400
POLYETHYLENE GLYCOL 8000
SILICON DIOXIDE
STARCH, CORN
TITANIUM DIOXIDE
TRIACETIN
Product Characteristics
Color orange (Orange-Red) Score no score
Shape ROUND Size 8mm
Flavor Imprint Code 699
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:62135-722-90 90 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA076267 08/20/2022
Labeler — Chartwell RX, LLC (079394054)

Revised: 07/2023 Chartwell RX, LLC

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