What is the maximum recommended dose of lisinopril (angiotensin-converting enzyme inhibitor)?

Maximum Dose of Lisinopril

The maximum recommended dose of lisinopril is 40 mg once daily for heart failure and hypertension, though doses up to 80 mg have been studied in hypertension without demonstrating greater efficacy. 1

FDA-Approved Maximum Dosing

The FDA label establishes clear maximum dosing parameters:

• Standard maximum dose: 40 mg once daily for all indications (hypertension, heart failure, and acute myocardial infarction) 1
• Doses up to 80 mg have been used in hypertension but do not appear to provide greater blood pressure reduction beyond 40 mg 1
• The usual dosage range for hypertension is 20-40 mg per day administered as a single daily dose 1

Heart Failure-Specific Dosing

For patients with heart failure, the evidence strongly supports targeting higher doses:

• Target dose: 20-40 mg once daily when used with diuretics and digitalis for systolic heart failure 1, 2
• Start at 5 mg once daily (or 2.5 mg if serum sodium <130 mEq/L), then titrate upward as tolerated to the maximum of 40 mg once daily 1
• Higher doses (30-35 mg daily) provide superior outcomes compared to lower doses (2.5-5 mg daily), including 12% lower risk of death or hospitalization and 24% fewer heart failure hospitalizations 3
• European guidelines recommend aiming for 30-35 mg once daily as the target dose in heart failure 4

Pediatric Maximum Dosing

For children ≥6 years with hypertension:

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

Renal Impairment Adjustments

Maximum doses must be reduced in renal dysfunction:

• CrCl >30 mL/min: No adjustment needed; maximum remains 40 mg daily 1
• CrCl 10-30 mL/min: Start at 5 mg (hypertension) or 2.5 mg (heart failure); titrate to maximum of 40 mg daily as tolerated 1
• CrCl <10 mL/min or hemodialysis: Start at 2.5 mg once daily; maximum 40 mg daily 1

Clinical Context for Dosing Decisions

The ATLAS trial demonstrated that higher doses are clinically superior in heart failure:

• High-dose lisinopril (32.5-35 mg daily) reduced major clinical events by 12% compared to low-dose (2.5-5 mg daily) over 39-58 months of treatment 3
• Aim for at least 50% of target dose (≥10 mg daily) to ensure clinical benefit in heart failure patients 2
• Titrate doses at intervals of not less than 2 weeks, monitoring blood pressure, renal function (creatinine, BUN), and potassium 4, 2

Important Caveats

• An increase in creatinine up to 50% above baseline is acceptable when initiating or uptitrating therapy 4, 2
• Asymptomatic hypotension does not require dose reduction 4
• If symptomatic hypotension occurs, consider reducing diuretic dose before lowering lisinopril dose 4
• Some ACE inhibitor is better than no ACE inhibitor—use the highest tolerated dose even if target cannot be reached 4