Lisinopril - Drug Monograph

Introduction

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in cardiovascular medicine. As a long-acting, once-daily medication, it represents a cornerstone therapy for hypertension, heart failure, and post-myocardial infarction management. First approved by the FDA in 1987, lisinopril remains one of the most prescribed antihypertensive agents worldwide due to its proven efficacy, favorable safety profile, and cardiovascular protective effects.

Mechanism of Action

Lisinopril competitively inhibits angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II—a potent vasoconstrictor. By reducing angiotensin II levels, lisinopril produces:

• Peripheral vasodilation
• Reduced aldosterone secretion
• Decreased sodium and water retention
• Inhibition of bradykinin degradation (contributing to vasodilation but also causing cough)

This results in decreased systemic vascular resistance, lowered blood pressure, reduced cardiac afterload, and improved cardiac output without reflex tachycardia.

Indications

FDA-approved indications:

• Hypertension (monotherapy or combination therapy)
• Heart failure (as adjunctive therapy)
• Acute myocardial infarction (within 24 hours in hemodynamically stable patients)
• Diabetic nephropathy in patients with type 2 diabetes and hypertension

Off-label uses include:

• Prevention of progressive renal dysfunction in non-diabetic nephropathies
• Migraine prophylaxis
• Scleroderma renal crisis prevention

Dosage and Administration

• Initial dose: 10 mg once daily
• Maintenance: 20-40 mg once daily
• Maximum dose: 80 mg daily

• Initial: 2.5-5 mg once daily
• Titrate to target dose of 20-40 mg daily

• 5 mg within 24 hours, then 5 mg after 24 hours, then 10 mg daily

• Renal impairment: Reduce dose for CrCl <30 mL/min
• Elderly: Start with lower doses (2.5-5 mg daily)
• Volume-depleted patients: Start with 2.5-5 mg daily

Pharmacokinetics

Contraindications

• History of angioedema related to previous ACE inhibitor treatment
• Hereditary or idiopathic angioedema
• Hypersensitivity to lisinopril or any component
• Concomitant use with aliskiren in patients with diabetes
• Second and third trimester of pregnancy (Category D)

Warnings and Precautions

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

• Angioedema: Can occur at any time during treatment
• Hypotension: Especially in volume-depleted patients
• Hyperkalemia: Risk increased with renal impairment, diabetes, or concomitant potassium-sparing agents
• Renal impairment: Monitor renal function, especially in patients with renal artery stenosis
• Neutropenia/agranulocytosis: Rare but serious
• Cough: Dry, persistent cough may develop

Drug Interactions

• Diuretics: Enhanced hypotensive effect
• Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
• NSAIDs: Reduced antihypertensive effect, increased renal impairment risk
• Lithium: Increased lithium levels
• Aliskiren: Increased hyperkalemia, hypotension, and renal impairment risk
• Angiotensin receptor blockers: Additive effects and adverse events

Adverse Effects

• Cough (up to 35%)
• Dizziness (12%)
• Headache (6-12%)
• Fatigue (3-10%)

• Angioedema
• Acute renal failure
• Hyperkalemia
• Hypotension
• Neutropenia/agranulocytosis
• Hepatic failure
• Pancreatitis

Monitoring Parameters

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

• Blood pressure at 2-4 week intervals until controlled
• Renal function and electrolytes within 2-4 weeks of initiation/dose change
• Potassium levels regularly, especially in high-risk patients
• Monitor for signs of angioedema, cough, or infection

Patient Education

• Take medication at the same time each day, with or without food
• Report any swelling of face, lips, tongue, or difficulty breathing immediately
• Persistent dry cough may occur and should be reported
• Rise slowly from sitting/lying position to avoid dizziness
• Avoid potassium supplements or salt substitutes without medical advice
• Report pregnancy or planning pregnancy immediately
• Maintain regular follow-up appointments for monitoring
• Do not stop medication abruptly without medical guidance

References

1. FDA Prescribing Information: Prinivil® (lisinopril) tablets 2. Chobanian AV, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252 3. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 1987;316:1429-1435 4. GISSI-3 Investigators. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343:1115-1122 5. Lewis EJ, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462 6. Micromedex® Healthcare Series. IBM Watson Health