What is the maximum daily dose of lisinopril (angiotensin-converting enzyme inhibitor) for a patient with severe hypertension or heart failure, considering factors such as renal function and history of hyperkalemia?

Maximum Daily Dose of Lisinopril

The maximum daily dose of lisinopril is 40 mg once daily for all indications including hypertension, heart failure, and post-myocardial infarction. 1

FDA-Approved Maximum Dosing

The FDA label explicitly states that lisinopril should be titrated "as tolerated to a maximum of 40 mg once daily" across all approved indications. 1 This represents the regulatory ceiling for lisinopril dosing, and doses above 40 mg have not been studied in clinical trials and are not recommended. 1

Target Dosing by Indication

Heart Failure with Reduced Ejection Fraction

• Target dose: 20-35 mg once daily for optimal mortality benefit 2, 3
• The ATLAS trial demonstrated that high-dose lisinopril (32.5-35 mg daily) was superior to low-dose (2.5-5 mg daily), reducing death or hospitalization by 12% and heart failure hospitalizations by 24% 2, 4
• At minimum, achieve 50% of target dose (10 mg daily) for meaningful clinical benefit 3
• Start at 5 mg once daily (or 2.5 mg if hyponatremic with sodium <130 mEq/L), then titrate every 2 weeks as tolerated 1, 3

Hypertension

• Target dose: 20-40 mg once daily 1
• Start at 10 mg once daily (or 5 mg if on diuretics) 1
• If blood pressure remains uncontrolled at 40 mg daily, add hydrochlorothiazide 12.5-25 mg rather than exceeding the maximum lisinopril dose 1

Post-Myocardial Infarction

• Target dose: 10 mg once daily (after initial titration) 1
• Initiate at 5 mg within 24 hours of symptom onset, followed by 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg daily for at least 6 weeks 1
• Start at 2.5 mg if systolic BP is 100-120 mmHg 1

Dose Adjustments for Renal Impairment

Critical consideration: Renal function directly impacts lisinopril dosing since the drug is eliminated primarily by the kidneys without hepatic metabolism. 5, 6

• CrCl >30 mL/min: No dose adjustment needed; maximum 40 mg daily 1
• CrCl 10-30 mL/min: Start at half the usual dose (5 mg for hypertension, 2.5 mg for heart failure/MI), titrate to maximum 40 mg daily as tolerated 1
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily, titrate cautiously to maximum 40 mg daily 1

The elimination half-life of lisinopril (12.6 hours) is prolonged in renal impairment, necessitating these adjustments. 5

Monitoring Requirements During Titration

Essential monitoring parameters to safely reach maximum doses:

• Check blood pressure, serum creatinine, and potassium within 5-7 days after initiation or dose increases 2
• An increase in creatinine up to 50% above baseline is acceptable and does not require dose reduction 3
• Monitor potassium levels closely, especially with concomitant potassium-sparing diuretics or supplements 3, 1
• Continue monitoring at 3 months, then every 6 months during maintenance therapy 2

Special Populations

Elderly Patients

• No specific dose reduction required based on age alone 7
• Dosages of 2.5-40 mg/day are effective, with 68-89% of elderly patients responding to treatment 7
• More gradual titration may be prudent due to increased risk of hypotension 7

Pediatric Patients (≥6 years)

• Maximum dose: 0.61 mg/kg once daily (not to exceed 40 mg total) 1
• Start at 0.07 mg/kg once daily (up to 5 mg) 1
• Not recommended in children <6 years or with GFR <30 mL/min/1.73m² 1

Common Pitfalls to Avoid

Underdosing is widespread in clinical practice, with less than 25% of heart failure patients ever titrated to target doses. 8 This represents a missed opportunity for mortality reduction, as the dose-response relationship is clear: higher doses provide greater benefits than lower doses. 2, 4

Do not exceed 40 mg daily under any circumstances. If blood pressure or heart failure symptoms remain uncontrolled at maximum dose, add complementary agents (diuretics, beta-blockers) rather than exceeding the FDA-approved maximum. 1

Asymptomatic hypotension does not require dose reduction. Only symptomatic hypotension warrants intervention, and in such cases, consider reducing diuretic dose before lowering lisinopril. 3

Never combine lisinopril with other ACE inhibitors or ARBs in acute settings (e.g., post-MI), as this increases adverse effects without added benefit. 3