Is there a benefit to taking Losartan (Losartan potassium) twice daily instead of once daily in some patients?

Twice-Daily Losartan Dosing: Benefits and Evidence

For most patients, there is no clinical benefit to taking losartan twice daily instead of once daily, as the standard once-daily dosing of losartan (up to 100 mg daily) is sufficient for blood pressure control and cardiovascular outcomes. 1

Evidence on Losartan Dosing

The 2022 AHA/ACC/HFSA guidelines for heart failure management recommend titration of guideline-directed medications to target doses shown to be efficacious in randomized controlled trials 2. For losartan, the guidelines indicate:

• Initial daily dose: 25-50 mg once daily
• Target dose: 50-150 mg once daily
• Mean dose achieved in clinical trials: 129 mg total daily 2

According to Praxis Medical Insights, the American College of Cardiology and American Heart Association recommend:

• Initial dose: 25-50 mg once daily
• Maximum dose: 50-150 mg once daily 1

Pharmacokinetics Supporting Once-Daily Dosing

Losartan's pharmacokinetic profile supports once-daily dosing:

• After oral administration, approximately 14% of losartan is converted to its active metabolite E3174
• E3174 is 10-40 times more potent than losartan
• E3174 has a terminal half-life of 6-9 hours, providing 24-hour efficacy 3
• The pharmacokinetics are linear and dose-proportional with no substantial changes with repetitive administration 3

Clinical Evidence on Twice-Daily vs. Once-Daily Dosing

A 2020 retrospective cohort study directly compared twice-daily versus once-daily dosing of losartan and found:

• No differences in systolic or diastolic blood pressure between twice-daily and once-daily dosing groups
• Absolute differences in mean systolic BP ranged from -1.8 to 0.7 mmHg
• Absolute differences in mean diastolic BP ranged from -1.1 to 0.1 mmHg
• All 95% confidence intervals crossed zero, indicating no statistically significant difference 4

Specific Scenarios Where Twice-Daily Dosing Might Be Considered

While once-daily dosing is generally sufficient, there are limited scenarios where twice-daily dosing might be considered:

1. Higher Total Daily Doses: For patients requiring doses above 100 mg daily (particularly in heart failure), splitting the dose may be reasonable

   • The HEAAL trial showed that 150 mg daily of losartan was superior to 50 mg daily for heart failure outcomes 1
   • When higher total daily doses are needed, splitting into twice-daily dosing may improve tolerability

2. Blood Pressure Control Issues: For patients with inadequate 24-hour blood pressure control on once-daily dosing

   • If blood pressure measurements show loss of control before the next dose is due

Practical Recommendations

1. Standard Approach: Start with losartan 25-50 mg once daily and titrate up to 100 mg once daily as needed for blood pressure control 1

2. Monitoring: Check blood pressure within 1-2 weeks after initiation or dose changes 1

3. Dose Adjustment: If blood pressure control is inadequate on 100 mg once daily:

   • Consider adding a second antihypertensive agent before splitting the losartan dose
   • If splitting the dose, divide the total daily amount into two equal doses (e.g., 50 mg twice daily instead of 100 mg once daily)

4. Heart Failure Patients: May benefit from higher target doses (up to 150 mg daily), which could be administered as divided doses 1

Conclusion

The evidence strongly supports once-daily dosing of losartan as the standard approach for most patients. Twice-daily dosing does not appear to offer improved effectiveness or safety for most patients 4. The pharmacokinetic profile of losartan, particularly the long half-life of its active metabolite E3174, provides sufficient 24-hour coverage with once-daily dosing 3.