Overview
11 DESCRIPTION Benazepril hydrochloride, USP is a white to off-white crystalline powder, soluble (> 100 mg/mL) in water, in ethanol, and in methanol. Its chemical name is benazepril 3-[[1-(ethoxy-carbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine-1-acetic acid monohydrochloride; its structural formula is Its empirical formula is C 24 H 28 N 2 O 5 •HCl and its...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Benazepril and benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. Benazeprilat has much greater ACE inhibitory activity than does benazepril. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.
Indications
- 1 INDICATIONS AND USAGE Benazepril hydrochloride tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs.
Common Doses
- 10 mg
- 5 mg
- 40 mg
- 30 mL
Dosage
2 DOSAGE AND ADMINISTRATION • Adult Patients: Initiate with 10 mg once daily (or 5 mg if patient is on diuretic). Titrate to 40 mg daily based on blood pressure response. ( 2.1 ) • Pediatric patients age 6 years and above with glomerular filtration rate (GFR) >30 mL/min/1.73 m 2 : Initiate with 0.2 mg/kg once daily. Maximum dose is 0.6 mg/kg once daily. • Renal Impairment: Initiate with 5 mg once daily in patients with GFR 3 mg/dL) ( 2 .2) 2.1 Recommended Dosage ADULTS The recommended initial dose for patients not receiving a diuretic is 10 mg once a day.
Black Box Warning
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue benazepril hydrochloride tablets as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions ( 5.1 )]. WARNING-FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue benazepril hydrochloride tablets as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )
Contraindications
- 4 CONTRAINDICATIONS Benazepril hydrochloride tablets are contraindicated in patients: • who are hypersensitive to benazepril or to any other ACE inhibitor • with a history of angioedema with or without previous ACE inhibitor treatment Benazepril hydrochloride tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer benazepril hydrochloride tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions (5.2)].
Side Effects
- 6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Benazepril hydrochloride has 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 similar in benazepril hydrochloride and placebo patients.
Interactions
- 7 DRUG INTERACTIONS • Diuretics: Excessive drop in blood pressure ( 7.1 ) • Antidiabetics: Increased risk of hypoglycaemia ( 7.2 ) • NSAIDS: Increased risk of renal impairment and loss of antihypertensive efficacy ( 7.3 ) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension and hyperkalemia ( 7.4 ) • Lithium: Symptoms of lithium toxicity ( 7.6 ) • Neprilysin Inhibitor: Increased risk of angioedema ( Error! Hyperlink reference not valid. ) • Gold: Nitritoid reactions ( 7.8 ) 7.