What is the maximum recommended dose of ramipril (angiotensin-converting enzyme inhibitor) for treating hypertension and heart failure?

Maximum Dose of Ramipril

The maximum recommended dose of ramipril is 10 mg twice daily (20 mg total daily dose) for heart failure post-myocardial infarction, and 20 mg daily for hypertension. 1, 2

Dosing by Indication

Hypertension

• Maximum dose: 20 mg per day (administered as a single dose or in two equally divided doses) 2
• Starting dose: 2.5 mg once daily 2
• Usual maintenance range: 2.5-20 mg daily 2
• If antihypertensive effect diminishes toward the end of the dosing interval with once-daily dosing, consider increasing the dose or switching to twice-daily administration 2

Heart Failure Post-Myocardial Infarction

• Target maximum dose: 5 mg twice daily (10 mg total daily dose) 1, 2
• Starting dose: 2.5 mg twice daily (or 1.25 mg twice daily if hypotensive) 1, 2
• Titrate upward over approximately 3-week intervals after tolerating the starting dose for one week 2
• This target dose of 5 mg twice daily was used in the AIRE trial and demonstrated mortality benefit 1

Chronic Heart Failure (European Guidelines)

• Maintenance dose range: 2.5-5 mg twice daily 1
• Starting dose: 1.25-2.5 mg daily 1
• The European Society of Cardiology guidelines recommend titrating to 5 mg twice daily as the target maintenance dose 1

Dose Adjustments for Special Populations

Renal Impairment

• Creatinine clearance >40 mL/min: Use usual dosing regimens 2
• Creatinine clearance ≤40 mL/min: 2
  • For hypertension: Initial dose 1.25 mg once daily; maximum 5 mg daily 2
  • For heart failure: Initial dose 1.25 mg once daily; may increase to 1.25 mg twice daily, up to maximum 2.5 mg twice daily 2
• In severe renal impairment, 25% of the usual dose produces full therapeutic levels of the active metabolite ramiprilat 2

Volume Depletion or Renal Artery Stenosis

• Start at 1.25 mg once daily regardless of indication 2
• Titrate according to blood pressure response 2

Clinical Context

The maximum doses are based on evidence from major clinical trials demonstrating mortality and morbidity benefits. The AIRE trial used ramipril 5 mg twice daily in post-MI patients with heart failure and showed significant survival benefit 1. For hypertension, doses up to 20 mg daily have been studied and shown to be effective and well-tolerated 3, 4, 5, 6.

Important monitoring: After initial dosing, observe patients for at least 2 hours and until blood pressure stabilizes for an additional hour 2. Check serum potassium and creatinine after 5-7 days of initiation or dose changes 1.