Benazepril - Drug Monograph

Introduction

Benazepril is an angiotensin-converting enzyme (ACE) inhibitor used primarily in the management of hypertension and heart failure. As a prodrug, it requires hepatic conversion to its active metabolite, benazeprilat, to exert its pharmacological effects. Benazepril represents an important therapeutic option in the renin-angiotensin-aldosterone system (RAAS) inhibition class of cardiovascular medications.

Mechanism of Action

Benazepril competitively inhibits angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This inhibition results in:

• Decreased systemic vascular resistance
• Reduced aldosterone secretion
• Increased bradykinin levels (contributing to some side effects)
• Diminished sodium and water retention

The net effect is reduced afterload and preload, leading to decreased blood pressure and improved cardiac output in heart failure patients.

Indications

FDA-approved indications:

• Hypertension (monotherapy or combination therapy)
• Heart failure (as adjunctive therapy)

Off-label uses (with supporting evidence):

• Diabetic nephropathy
• Post-myocardial infarction left ventricular dysfunction
• Chronic kidney disease progression delay

Dosage and Administration

• Initial dose: 5-10 mg once daily
• Maintenance dose: 20-40 mg daily (single or divided doses)
• Maximum dose: 80 mg daily

• Initial dose: 2.5-5 mg once daily
• Target dose: 20-40 mg daily

• Renal impairment: CrCl <30 mL/min: Start with 5 mg daily
• Hepatic impairment: No specific adjustment needed
• Geriatric: Start with lower doses (2.5-5 mg daily)
• Pediatric: Not recommended under 6 years; 6+ years: 0.2 mg/kg daily

Pharmacokinetics

Contraindications

• History of angioedema related to previous ACE inhibitor therapy
• Hereditary or idiopathic angioedema
• Concomitant use with aliskiren in patients with diabetes
• Hypersensitivity to benazepril or any ACE inhibitor
• Pregnancy (second and third trimesters)

Warnings and Precautions

• Fetal toxicity: Can cause injury and death to developing fetus
• Discontinue when pregnancy is detected

• Angioedema: Monitor for swelling of face, lips, tongue, or larynx
• Hypotension: Risk increased in volume-depleted patients
• Renal impairment: Monitor renal function; risk of acute kidney injury
• Hyperkalemia: Particularly in renal impairment, diabetes, or with potassium-sparing diuretics
• Cough: Persistent dry cough may develop
• Neutropenia/agranulocytosis: Rare but serious; monitor CBC in at-risk patients
• Surgery/anesthesia: May potentiate hypotension effects

Drug Interactions

• Diuretics: Enhanced hypotensive effect
• Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
• Lithium: Increased lithium levels and toxicity
• NSAIDs: Reduced antihypertensive effect; increased renal impairment risk
• Aliskiren: Increased hyperkalemia, hypotension, and renal impairment risk
• Gold injections: Nitritoid reactions reported

• Antidiabetic agents: Enhanced hypoglycemic effects
• Sympathomimetics: Reduced antihypertensive effect
• mTOR inhibitors: Increased angioedema risk

Adverse Effects

• Cough (5-10%)
• Headache (3-6%)
• Dizziness (3-4%)
• Fatigue (2-3%)
• Nausea (1-2%)

• Angioedema (0.1-0.5%)
• Acute renal failure
• Severe hypotension
• Hyperkalemia
• Neutropenia/agranulocytosis
• Hepatic failure (rare)
• Pancreatitis (rare)

Monitoring Parameters

• Blood pressure
• Renal function (BUN, creatinine, electrolytes)
• Potassium levels
• Pregnancy test in women of childbearing potential

• Blood pressure at each visit
• Renal function and electrolytes within 2-4 weeks of initiation/dose change, then periodically
• Potassium levels, especially in at-risk patients
• Monitor for cough and angioedema symptoms
• CBC if symptoms suggest infection

• Regular blood pressure checks
• Awareness of angioedema symptoms
• Weight monitoring in heart failure patients

Patient Education

• Take medication at the same time each day
• Report any swelling of face, lips, tongue, or throat immediately
• Persistent dry cough may develop
• Rise slowly from sitting/lying position to prevent dizziness
• Avoid potassium supplements unless prescribed
• Maintain adequate hydration
• Regular blood pressure monitoring
• Use effective contraception; report suspected pregnancy immediately
• Inform all healthcare providers about benazepril use
• Do not stop medication without consulting prescriber

• Sodium restriction
• Regular exercise
• Weight management
• Alcohol moderation
• Smoking cessation

References

1. FDA Prescribing Information: Lotensin (benazepril hydrochloride) 2. Chobanian AV, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252. 3. Mann JF, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. Lancet. 2008;372(9638):547-553. 4. McMurray JJ, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2012;33(14):1787-1847. 5. Drug Interaction Facts: Facts & Comparisons. Wolters Kluwer Health. 6. Micromedex Solutions. Truven Health Analytics. 7. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248.