Is it safe to take Lisinopril (angiotensin-converting enzyme inhibitor) twice a day?

Lisinopril Should Not Be Taken Twice Daily

Lisinopril should be administered once daily, not twice daily, as it is designed for 24-hour efficacy with a single daily dose. 1, 2

Proper Dosing of Lisinopril

• Lisinopril is specifically formulated for once-daily administration with a long duration of action that provides 24-hour blood pressure control 1, 3
• The FDA-approved dosing for lisinopril ranges from 2.5-40 mg once daily, with no recommendation for twice-daily dosing 1
• For hypertension, the recommended starting dose is 10 mg once daily, which can be titrated up to a maximum of 40 mg once daily 2, 1
• For heart failure, the starting dose is lower (2.5-5 mg once daily) with gradual titration to 20-35 mg once daily 4

Pharmacokinetic Rationale

• Lisinopril has a long elimination half-life of approximately 12.6 hours, which supports once-daily dosing 3, 5
• The drug provides sustained ACE inhibition for at least 24 hours after a single dose, making twice-daily administration unnecessary 6, 3
• Peak effects occur 6-8 hours after administration, but the antihypertensive effect persists for a full 24 hours 3, 7

Risks of Twice-Daily Dosing

• Administering lisinopril twice daily could lead to excessive ACE inhibition, increasing the risk of hypotension, especially in volume-depleted patients 2
• Twice-daily dosing may increase the risk of adverse effects such as:
  • Symptomatic hypotension 2
  • Worsening renal function 2
  • Hyperkalemia 2
  • Angioedema (rare but serious) 8

Comparison with Other ACE Inhibitors

• Unlike captopril, which requires multiple daily doses due to its shorter half-life, lisinopril was specifically developed to allow once-daily dosing 5, 7
• The European Journal of Heart Failure guidelines specifically list lisinopril as a once-daily medication, while other ACE inhibitors like captopril and enalapril may require twice-daily dosing 4
• For patients who require twice-daily ACE inhibitor dosing, other options such as captopril (6.25-50 mg three times daily) or enalapril (2.5-10 mg twice daily) would be more appropriate choices 4

Alternative Approaches

• If blood pressure control is inadequate with the maximum recommended once-daily dose of lisinopril:
  • Add a different class of antihypertensive agent rather than splitting the dose 2
  • Consider switching to a different ACE inhibitor with recommended twice-daily dosing 4
  • For heart failure patients requiring additional renin-angiotensin system blockade, adding an aldosterone antagonist would be more appropriate than increasing lisinopril frequency 2

Monitoring Recommendations

• When initiating or adjusting lisinopril dosage, monitor:
  • Blood pressure 8
  • Renal function (urea, creatinine) 4, 8
  • Serum potassium 8
• Dose adjustments should be made at intervals of not less than 2 weeks to allow full assessment of effects 4, 8