What is the maximum dose of ramipril (Angiotensin-Converting Enzyme inhibitor)?

Maximum Dose of Ramipril

The maximum dose of ramipril is 20 mg per day for hypertension, and 10 mg per day (5 mg twice daily) for heart failure post-myocardial infarction. 1

Dosing Guidelines by Indication

Hypertension

• Initial dose: 2.5 mg once daily for patients not receiving a diuretic 1
• Maintenance dose range: 2.5 mg to 20 mg per day, administered as a single dose or in two equally divided doses 1
• If blood pressure control diminishes toward the end of the dosing interval, consider twice daily administration 1
• If blood pressure is not adequately controlled with ramipril alone, a diuretic can be added 1
• In clinical trials, 41% of patients required only 2.5 mg daily and 81% required ≤5 mg daily for blood pressure control 2

Heart Failure Post-Myocardial Infarction

• Initial dose: 2.5 mg twice daily (5 mg total daily) 1
• If hypotension occurs at this dose, may reduce to 1.25 mg twice daily 1
• Target dose: 5 mg twice daily (10 mg total daily), with dosage increases approximately 3 weeks apart 1
• In the AIRE study, ramipril was used at doses of 2.5 mg twice daily up to 5 mg twice daily 3

Dosing in Special Populations

Renal Impairment

• For patients with creatinine clearance >40 mL/min: follow usual regimens 1
• For patients with creatinine clearance ≤40 mL/min: 25% of the usual dose is expected to produce full therapeutic levels 1
• For hypertension with renal impairment: initial dose 1.25 mg once daily, maximum 5 mg total daily 1
• For heart failure with renal impairment: initial dose 1.25 mg once daily, maximum 2.5 mg twice daily 1

Volume Depletion or Renal Artery Stenosis

• Initial dose: 1.25 mg once daily 1
• Adjust dosage according to blood pressure response 1

Efficacy and Clinical Evidence

• Ramipril is a long-acting ACE inhibitor that is hydrolyzed after absorption to form the active metabolite ramiprilat 4
• In hypertensive patients, daily doses of 2.5 to 20 mg are usually effective in reducing high blood pressure 4
• The 2020 ACC/AHA guidelines identify 10 mg once daily as the target dose for ramipril in heart failure with reduced ejection fraction (HFrEF) 3
• Studies show that achieving target doses of ACE inhibitors in heart failure patients results in better clinical outcomes 3

Administration Considerations

• Ramipril capsules can be swallowed whole or opened and contents sprinkled on applesauce or mixed in water/apple juice 1
• Such mixtures can be pre-prepared and stored for up to 24 hours at room temperature or up to 48 hours under refrigeration 1
• Concomitant administration with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases in serum potassium 1

Monitoring Recommendations

• Monitor blood pressure response regularly to guide dose adjustments 1
• After initial dose, observe patient under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour 1
• Monitor renal function and electrolytes within 1-2 weeks after initiating therapy or changing doses 5

Common Pitfalls and Caveats

• Hypotension may occur after the initial dose, particularly in patients on diuretic therapy, with volume depletion, or with heart failure 1
• If possible, reduce the dose of any concomitant diuretic to diminish the likelihood of hypotension 1
• The appearance of hypotension after the initial dose does not preclude subsequent careful dose titration 1
• Never combine two ACE inhibitors as this increases the risk of adverse effects without providing additional benefits 5
• Avoid combination of ACE inhibitors with ARBs or aldosterone antagonists due to high risk of hyperkalemia 5