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

Lisinopril Side Effects

Lisinopril commonly causes side effects including cough, dizziness, headache, hypotension, and hyperkalemia, with certain serious adverse reactions requiring immediate discontinuation. 1

Common Side Effects

• Headache (3.8% higher than placebo), dizziness (3.5% higher than placebo), and cough (2.5% higher than placebo) are the most frequently reported side effects in hypertension trials 1
• Gastrointestinal effects include pancreatitis, constipation, flatulence, dry mouth, and diarrhea 1
• Fatigue and asthenia (weakness) are commonly reported systemic effects 1, 2
• Hypotension is particularly common in heart failure patients (3.8% higher than placebo) and in patients with acute myocardial infarction (5.3% higher than placebo) 1

Cardiovascular Effects

• Unlike beta-blockers or certain calcium channel blockers, lisinopril does not directly lower heart rate as it doesn't affect the sinoatrial node or cardiac conduction system 3
• Orthostatic effects (blood pressure drop when standing) can occur, particularly with the first dose 1, 4
• Chest pain was reported in heart failure patients (2.1% higher than placebo) 1

Renal and Electrolyte Abnormalities

• Hyperkalemia (serum potassium >5.7 mEq/L) occurs in 2.2% of hypertensive patients and 4.8% of heart failure patients 1
• Renal dysfunction is more common in patients with acute myocardial infarction (1.3% higher than those not taking lisinopril) 1
• Minor increases in blood urea nitrogen and serum creatinine occur in about 2% of hypertensive patients, more commonly in those on concomitant diuretics or with renal artery stenosis 1
• Inappropriate antidiuretic hormone secretion has been reported 1

Hematologic Effects

• Small decreases in hemoglobin and hematocrit are common 1
• Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia, and thrombocytopenia have been reported 1

Dermatologic and Hypersensitivity Reactions

• Angioedema is a serious, potentially life-threatening reaction that requires immediate discontinuation of the medication 5
• Other skin reactions include urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, and pruritus 1
• Severe reactions like toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported 1

Special Senses Effects

• Visual disturbances including visual loss, diplopia, and blurred vision 1
• Tinnitus, photophobia, taste disturbances, and olfactory disturbance have been reported 1

Metabolic Effects

• Gout has been reported 1
• Unlike thiazide diuretics, lisinopril does not produce hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia 6

Important Precautions and Contraindications

• Lisinopril should not be prescribed to patients with a history of angioedema with previous ACE inhibitor use 5
• Patients should not be given lisinopril if they have experienced life-threatening adverse reactions (angioedema or anuric renal failure) during previous exposure to the drug or if they are pregnant 5
• Caution is advised in patients with very low systemic blood pressures (systolic blood pressure less than 80 mm Hg), markedly increased serum creatinine (greater than 3 mg per dL), bilateral renal artery stenosis, or elevated levels of serum potassium (greater than 5.5 mmol per liter) 5
• Treatment should not be initiated in hypotensive patients at immediate risk of cardiogenic shock 5

Monitoring Recommendations

• Renal function and serum potassium should be assessed within 1-2 weeks of initiation of therapy and periodically thereafter, especially in patients with pre-existing hypotension, hyponatremia, diabetes mellitus, or azotemia, or in those taking potassium supplements 5
• Fluid status should be carefully monitored as fluid retention can blunt therapeutic effects and fluid depletion can potentiate adverse effects 5

Dosing Considerations

• Treatment should be initiated at low doses, followed by gradual increments if lower doses have been well tolerated 5
• Dose adjustment is necessary when creatinine clearance is less than 30 mL/min due to potential accumulation 2

Human experience indicates that lisinopril is generally well tolerated with a good safety profile when used appropriately and with proper monitoring 6.