Can Ramipril (Angiotensin-Converting Enzyme Inhibitor) be taken twice a day (bid)?

Ramipril Administration: Once vs. Twice Daily Dosing

Yes, ramipril can be taken twice daily (bid) in specific clinical scenarios, though once-daily dosing is the standard regimen for most patients with hypertension.

FDA-Approved Dosing Regimens

• For hypertension, ramipril can be administered as "a single dose or in two equally divided doses" with a maintenance dosage range of 2.5-20 mg per day 1
• In patients treated once daily where the antihypertensive effect diminishes toward the end of the dosing interval, twice daily administration should be considered 1
• For heart failure post-myocardial infarction, ramipril is specifically recommended as twice daily dosing, starting at 2.5 mg twice daily (5 mg total daily dose) with a target dose of 5 mg twice daily 1

Clinical Evidence Supporting Different Dosing Schedules

• The 2020 ACC/AHA guidelines specifically list ramipril's target dose for heart failure with reduced ejection fraction (HFrEF) as 10 mg once daily 2
• In clinical trials for heart failure, ramipril has been used at a twice daily dose of 5 mg, while in the HOPE study (for cardiovascular prevention), it was used as 10 mg once at bedtime 3
• A randomized crossover trial comparing once-daily (10 mg) versus twice-daily (5 mg bid) dosing found that both regimens effectively lowered blood pressure to a similar extent over a 24-hour period 3

Factors Affecting Dosing Decision

• Patient-specific factors that may favor twice-daily dosing include:

  • Heart failure post-myocardial infarction (specifically indicated for bid dosing) 1
  • Patients whose blood pressure control diminishes toward the end of a once-daily dosing interval 1
  • Patients with renal impairment who require dose adjustment 1

• Pharmacokinetic considerations:

  • Ramipril is a long-acting ACE inhibitor that can generally maintain therapeutic effect over 24 hours with once-daily dosing 4, 5
  • Renal excretion largely determines the drug's duration of action, which may affect dosing frequency in patients with impaired kidney function 5

Clinical Recommendations

• For most hypertensive patients, once-daily dosing of ramipril is sufficient and preferred for adherence 4
• For post-MI heart failure patients, follow the specific twice-daily dosing regimen starting at 2.5 mg bid with target of 5 mg bid 1
• Monitor blood pressure response throughout the dosing interval; if control wanes before the next dose, consider switching to twice-daily administration 1
• When using twice-daily dosing, divide the total daily dose equally (e.g., 10 mg daily would become 5 mg twice daily) 1, 3

Important Considerations

• Always titrate ramipril to the maximally tolerated dose to achieve optimal clinical outcomes 2
• For heart failure patients, therapies must be initiated and titrated to maximally tolerated doses to improve mortality and morbidity outcomes 2
• The target dose of ramipril for heart failure is 10 mg daily, with 5 mg daily considered 50% of target dose 2
• When switching between once and twice daily dosing, maintain the same total daily dose unless clinical factors indicate otherwise 3