What are the side effects of lisinopril (angiotensin-converting enzyme inhibitor)?

Lisinopril Side Effects

Lisinopril's most serious side effect is angioedema, which requires immediate discontinuation; common side effects include headache, dizziness, cough, hypotension, and hyperkalemia, with careful monitoring of renal function and potassium levels essential during therapy. 1, 2

Serious and Life-Threatening Reactions

Angioedema

• Angioedema is a potentially life-threatening hypersensitivity reaction that mandates immediate discontinuation of lisinopril. 1
• The American College of Cardiology explicitly contraindicates lisinopril in patients with any history of angioedema from previous ACE inhibitor use. 1

Hypotension

• Hypotension occurs significantly more frequently in certain populations, particularly in heart failure patients (3.8% more than placebo) and acute MI patients (5.3% more than controls). 2
• First-dose hypotensive episodes are uncommon in hypertensive patients with normal renal function (0.6%), but increase to 6.7% in those with impaired renal function. 3

Renal Dysfunction

• Renal dysfunction manifests as increases in blood urea nitrogen and serum creatinine, occurring in approximately 2% of hypertensive patients and 11.6% of heart failure patients on concomitant diuretics. 2
• Acute MI patients treated with lisinopril show higher incidence of renal dysfunction (2.4% versus 1.1% in placebo), defined as creatinine concentration exceeding 3 mg/dL or doubling of baseline. 2
• The American College of Cardiology recommends particular caution in patients with bilateral renal artery stenosis, as these patients are at markedly increased risk. 1

Common Side Effects

Cardiovascular and Hemodynamic

• Unlike beta-blockers or non-dihydropyridine calcium channel blockers, lisinopril does not directly lower heart rate because it doesn't affect the sinoatrial node or cardiac conduction system. 1
• Chest pain occurs 2.1% more frequently than placebo in heart failure patients. 2

Respiratory

• Cough is a class-related adverse effect occurring 2.5% more frequently than placebo in hypertensive patients. 2
• This dry, persistent cough results from ACE inhibition and bradykinin accumulation. 4

Neurological

• Headache occurs 3.8% more frequently than placebo. 2
• Dizziness occurs 3.5% more frequently than placebo in hypertensive patients. 2

Gastrointestinal

• Diarrhea, constipation, flatulence, dry mouth, and pancreatitis have been reported at rates ≥1%. 2

Metabolic and Laboratory Abnormalities

Hyperkalemia

• Hyperkalemia (serum potassium >5.7 mEq/L) occurs in 2.2% of hypertensive patients and 4.8% of heart failure patients. 2
• The American College of Cardiology mandates assessment of serum potassium within 1-2 weeks of therapy initiation and periodically thereafter, especially in high-risk patients taking potassium supplements, those with diabetes, or those with pre-existing azotemia. 1

Hematologic Effects

• Small decreases in hemoglobin and hematocrit occur (mean decreases approximately 0.4 g% and 1% respectively). 2
• Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia, and thrombocytopenia have been reported. 2

Dermatologic Reactions

• Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, and pruritus occur at rates ≥1%. 2
• Severe reactions including toxic epidermal necrolysis, Stevens-Johnson syndrome, and cutaneous pseudolymphoma are rare but documented. 2

Other Notable Side Effects

• Fatigue and asthenia occur at rates ≥1%. 2
• Visual disturbances including visual loss, diplopia, blurred vision, and photophobia have been reported. 2
• Taste and olfactory disturbances occur. 2
• Impotence has been reported. 2
• A symptom complex resembling autoimmune disease (positive ANA, elevated ESR, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia) may occur. 2

Critical Monitoring Requirements

Initial and Ongoing Assessment

• Renal function and serum potassium must be assessed within 1-2 weeks of starting therapy and monitored periodically, with heightened vigilance in patients with pre-existing hypotension, hyponatremia, diabetes mellitus, or azotemia. 1
• Fluid status requires careful monitoring as fluid retention blunts therapeutic effects while fluid depletion potentiates adverse effects. 1

Dosing Strategy to Minimize Adverse Effects

• The American College of Cardiology recommends initiating treatment at low doses with gradual increments only after lower doses are well tolerated. 1
• This titration strategy reduces the risk of hypotension and other dose-related adverse effects. 1

Discontinuation Rates

• In hypertensive patients, 5.7% discontinued therapy due to adverse reactions, with cough and dizziness being the most common reasons. 2, 3
• In heart failure patients, 11% discontinued over up to four years of treatment, though 12-week controlled trials showed similar discontinuation rates between lisinopril (8.1%) and placebo (7.7%). 2