What are the side effects of lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor)?

Side Effects of Lisinopril

The most common side effects of lisinopril include cough, hypotension, renal insufficiency, hyperkalemia, syncope, and angioedema, with cough being particularly frequent (occurring in up to 20% of patients). 1, 2

Common Side Effects

Lisinopril, an ACE inhibitor commonly used for hypertension and heart failure, is associated with several side effects:

• Respiratory system:

  • Persistent dry cough (occurs in up to 20% of patients) 1
  • This is a class effect of ACE inhibitors due to increased bradykinin levels

• Cardiovascular system:

  • Hypotension (especially first-dose hypotension)
  • Syncope (fainting)
  • Orthostatic effects 2

• Renal system:

  • Increased serum creatinine (small increases up to 50% above baseline are generally acceptable) 3
  • Renal insufficiency (more common in patients with pre-existing renal disease, bilateral renal artery stenosis, or those taking concomitant diuretics) 1

• Metabolic effects:

  • Hyperkalemia (serum potassium >5.7 mEq/L occurs in 2.2% of hypertensive patients and 4.8% of heart failure patients) 2
  • Inappropriate antidiuretic hormone secretion 2

Less Common but Serious Side Effects

• Angioedema (swelling of face, lips, tongue, throat)

  • Can be life-threatening and requires immediate medical attention
  • Occurs in <1% of patients but more frequently in Black patients and women 1, 4
  • Contraindicated in patients with previous ACE inhibitor-induced angioedema 1

• Hematologic abnormalities (rare):

  • Bone marrow depression
  • Hemolytic anemia
  • Leukopenia/neutropenia
  • Thrombocytopenia 2

• Dermatologic reactions:

  • Rash
  • Urticaria
  • Photosensitivity
  • Rare but severe: Stevens-Johnson syndrome and toxic epidermal necrolysis 2

Gastrointestinal Side Effects

• Pancreatitis
• Constipation
• Flatulence
• Dry mouth
• Diarrhea 2

Neurological and Sensory Side Effects

• Headache (reported in 3.8% more patients than placebo)
• Dizziness (reported in 3.5% more patients than placebo)
• Visual disturbances (visual loss, diplopia, blurred vision)
• Tinnitus
• Taste disturbances 2

Special Considerations

Renal Function

• Regular monitoring of renal function is recommended:
  1. Before starting treatment
  2. 1-2 weeks after each dose increment
  3. At 3-6 month intervals
  4. When adding other medications that may affect renal function
  5. More frequent monitoring in patients with renal dysfunction 1

Contraindications

• Bilateral renal artery stenosis
• Previous angioedema with ACE inhibitor therapy
• Pregnancy (can cause fetal harm) 1

Drug Interactions

• Potassium-sparing diuretics may increase risk of hyperkalemia
• NSAIDs may reduce antihypertensive effect and increase risk of renal dysfunction
• Diuretics may enhance hypotensive effect (especially first dose) 1, 3

Monitoring Recommendations

• Blood pressure: Monitor for hypotension, especially after first dose
• Renal function: Check serum creatinine and BUN before starting, 1-2 weeks after initiation, and periodically thereafter
• Electrolytes: Monitor potassium levels, especially in patients with renal impairment or those taking potassium supplements or potassium-sparing diuretics
• Symptoms: Assess for development of cough, angioedema, or other side effects 1, 3

Dosing Considerations

• Start with low doses (2.5-5 mg daily) and titrate gradually
• Lower initial doses recommended for patients with:
  • Heart failure
  • Renal impairment (especially when creatinine clearance <30 mL/min)
  • Elderly patients
  • Those receiving diuretics 1, 3

Common Pitfalls

• Premature discontinuation due to small increases in creatinine or asymptomatic hypotension
• Failure to recognize angioedema early
• Not adjusting dose in patients with renal impairment
• Inadequate monitoring of potassium levels when combining with potassium-sparing diuretics 3

Remember that despite these potential side effects, ACE inhibitors like lisinopril provide significant benefits in reducing morbidity and mortality in patients with hypertension, heart failure, and post-myocardial infarction.