Maximum Recommended Dose of Ramipril
The maximum recommended 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
Hypertension Dosing
- For hypertension, ramipril dosing ranges from 2.5 mg to 20 mg per day, administered as a single dose or in two equally divided doses 1
- The initial dose is 2.5 mg once daily in patients not receiving a diuretic, with titration based on blood pressure response 1
- If the antihypertensive effect diminishes toward the end of the dosing interval with once-daily administration, consider increasing the dose or switching to twice-daily administration 1
- Clinical trials demonstrate that ramipril 2.5 to 20 mg daily effectively reduces and maintains blood pressure control during long-term treatment 2
- In real-world practice, 81% of hypertensive patients required ≤5 mg once daily for adequate blood pressure control 3
Heart Failure Post-Myocardial Infarction Dosing
- For heart failure post-MI, the target dose is 5 mg twice daily (10 mg total daily dose), with a starting dose of 2.5 mg twice daily 1
- Patients who become hypotensive may be switched to 1.25 mg twice daily initially 1
- Titrate upward toward the target dose over approximately 3-week intervals after one week at the starting dose 1
- The maximum dose in this indication is lower than hypertension due to the increased risk of hypotension in post-MI heart failure patients 1
Special Populations Requiring Dose Adjustment
Renal Impairment
- For patients with creatinine clearance >40 mL/min, use usual dosing regimens 1
- For patients with creatinine clearance ≤40 mL/min, 25% of the usual dose produces full therapeutic levels of the active metabolite ramiprilat 1
- In hypertensive patients with renal impairment, start at 1.25 mg once daily and titrate to a maximum of 5 mg daily 1
- In heart failure patients with renal impairment, start at 1.25 mg once daily, increase to 1.25 mg twice daily, with a maximum of 2.5 mg twice daily 1
Volume Depletion or Renal Artery Stenosis
- If volume depletion or renal artery stenosis is suspected, initiate dosing at 1.25 mg once daily regardless of indication 1
- This lower starting dose reduces the risk of excessive hypotension in these high-risk scenarios 1
Clinical Context from Major Trials
- The HOPE trial used ramipril 10 mg daily and demonstrated significant cardiovascular benefits, including reduction in MI, stroke, or cardiovascular death (RR 0.75, p=0.0004) 4
- Lower doses (ramipril 1.25 mg daily) in the Marre 2004 study showed no significant mortality benefit, highlighting the importance of adequate dosing 4
- Ramipril 10 mg once daily shows comparable antihypertensive efficacy to usual therapeutic dosages of captopril, enalapril, and atenolol 2, 5
Important Safety Considerations
- Avoid concomitant use with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics, as this increases the risk of hyperkalemia 1
- Observe patients for at least 2 hours after the initial dose and until blood pressure stabilizes for an additional hour, particularly in heart failure patients 1
- Consider reducing concomitant diuretic doses when initiating ramipril to minimize hypotension risk 1