What is the recommended dose of Captopril (Angiotensin-Converting Enzyme inhibitor) for adults with hypertension or heart failure?

Captopril Dosing for Hypertension and Heart Failure

For hypertension, start captopril at 25 mg twice or three times daily and titrate to 50 mg three times daily; for heart failure, initiate at 6.25 mg three times daily and target 50 mg three times daily. 1

Hypertension Dosing

Initial dose: Start with 25 mg twice or three times daily 1. The FDA label explicitly states this as the standard starting dose for most hypertensive patients, though lower doses (12.5 mg three times daily) have proven effective in clinical trials 2.

Titration schedule:

• If blood pressure is not adequately controlled after 1-2 weeks, increase to 50 mg twice or three times daily 1
• The usual effective dose range is 25-150 mg divided into 2-3 daily doses 1
• Maximum daily dose should not exceed 450 mg 1

Key considerations for hypertension:

• Captopril demonstrates a flat dose-response curve, meaning doses above 150 mg/day rarely provide additional benefit 3
• Adding a thiazide diuretic (e.g., hydrochlorothiazide 25 mg daily) significantly enhances antihypertensive response if monotherapy at 50 mg three times daily is insufficient 1, 2
• Take captopril one hour before meals to optimize absorption 1

Heart Failure Dosing

Initial dose: Start with 6.25 mg three times daily in patients with heart failure, particularly those on vigorous diuretic therapy or with potential volume depletion 1, 4.

Titration protocol:

• Increase to 12.5 mg three times daily after tolerating initial dose 1
• Progress to 25 mg three times daily over the next several days 1
• Target maintenance dose: 50 mg three times daily (150 mg total daily) 1, 4
• The SAVE trial demonstrated mortality benefit with captopril 50 mg three times daily (mean daily dose 127 mg) in post-MI patients with left ventricular dysfunction 4

Titration timing:

• Double the dose at intervals of not less than 2 weeks 4
• After reaching 50 mg three times daily, delay further increases for at least 2 weeks to assess response 1
• Maximum daily dose: 450 mg 1

Critical Safety Considerations

Before initiating therapy:

• Check baseline renal function (creatinine), potassium, and blood pressure 4
• Consider reducing or withholding diuretics for 24 hours before first dose if patient is volume depleted 4
• Seek specialist advice if creatinine >2.5 mg/dL (>221 μmol/L), potassium >5.0 mmol/L, or systolic BP <90 mmHg 4

Monitoring schedule:

• Check potassium and creatinine after 5-7 days, then after each dose increase 4
• Recheck every 5-7 days until values stabilize 4
• Long-term monitoring at 3 months, then every 6 months 4

Acceptable changes:

• Creatinine increases up to 50% above baseline (or up to 3 mg/dL, whichever is greater) are acceptable 5
• Small increases in blood urea nitrogen and creatinine are expected and do not require discontinuation unless substantial 4

Special Populations and Situations

Severe hypertension (accelerated/malignant):

• May initiate at 25 mg twice or three times daily under close supervision 1
• Can increase dose every 24 hours if clinically necessary 1
• Continue diuretic but stop other antihypertensives 1

Post-myocardial infarction:

• Initiate as early as 3 days post-MI 1
• Start with single 6.25 mg dose, then 12.5 mg three times daily 1
• Target 50 mg three times daily over several weeks 1, 4

Diabetic nephropathy:

• Recommended dose: 25 mg three times daily for long-term use 1

Common Pitfalls to Avoid

First-dose hypotension: The most critical adverse effect, particularly in heart failure patients. Mitigate by:

• Starting with 6.25 mg (or even 1 mg in extremely sensitive patients) 6
• Avoiding excessive diuresis before initiation 4, 1
• Administering first dose in evening when supine (though evidence is limited) 4

Inadequate dosing: Many patients receive subtherapeutic doses. Remember:

• Target the evidence-based doses from major trials (50 mg three times daily for heart failure) 4
• "Some ACE inhibitor is better than no ACE inhibitor," but aim for target doses 4
• Higher doses (up to 150 mg daily) in ATLAS trial showed better outcomes than lower doses 4

Premature discontinuation for cough: ACE inhibitor-induced cough rarely requires discontinuation 4. First exclude pulmonary edema as the cause before attributing cough to the medication 4.