Split-Dose Lisinopril Regimen: Not Recommended
Lisinopril should be administered as a single daily dose, not split into morning and evening doses, as the drug is specifically designed and FDA-approved for once-daily dosing with a duration of action lasting at least 24 hours. 1
Pharmacokinetic Rationale
Lisinopril has a prolonged duration of action with peak effects occurring 6-8 hours after administration and antihypertensive effects persisting for at least 24 hours, making split dosing pharmacologically unnecessary. 2, 3
The elimination half-life of lisinopril is 12.6 hours in patients with normal renal function, which supports once-daily administration. 4, 3
Steady-state concentrations are achieved within 2-3 days of once-daily dosing without significant accumulation in patients with normal renal function. 2
FDA-Approved Dosing Guidelines
The FDA-approved dosing for lisinopril is:
Hypertension: 10 mg once daily initially, with usual maintenance doses of 20-40 mg once daily (maximum 80 mg once daily). 1
Heart failure: 5 mg once daily initially (2.5 mg in patients with hyponatremia), titrated to a maximum of 40 mg once daily. 1
Post-myocardial infarction: 5 mg once daily, advancing to 10 mg once daily for long-term therapy. 1
Evidence-Based Target Dosing
Major clinical trials demonstrating mortality and morbidity benefits used once-daily dosing regimens, with the ATLAS trial showing that high-dose lisinopril (32.5-35 mg once daily) was superior to low-dose (2.5-5 mg once daily) in reducing heart failure hospitalizations and combined mortality/morbidity endpoints. 5, 6
The mean daily dose achieved in the landmark SOLVD trial was 16.6 mg total daily, administered as a single dose. 5
Clinical Implications of Split Dosing
Splitting the 15 mg total daily dose (10 mg + 5 mg) offers no pharmacologic advantage and may:
- Reduce medication adherence due to increased dosing complexity
- Create confusion about the total daily dose being administered
- Deviate from evidence-based protocols that demonstrated clinical benefit with once-daily administration 5, 6
Recommended Approach
If the patient requires 15 mg daily of lisinopril, administer the entire dose once daily in the morning. 1, 3
Monitor blood pressure throughout the 24-hour dosing interval to ensure adequate control, particularly measuring just prior to the next dose (trough effect). 5
If blood pressure control is inadequate at trough, consider increasing to 20 mg once daily rather than splitting doses. 1
Titrate doses gradually every 1-2 weeks based on blood pressure response, renal function, and electrolytes. 5
Important Monitoring Considerations
Check renal function and serum potassium within 1-2 weeks after initiating therapy or changing doses, as ACE inhibitors can cause hyperkalemia and renal dysfunction. 5
Avoid concomitant use with potassium-sparing diuretics during initiation unless specifically indicated for persistent hypokalemia. 5
In patients with renal impairment (creatinine clearance 10-30 mL/min), reduce the initial dose to 5 mg once daily and titrate cautiously. 1