Can losartan (angiotensin II receptor antagonist) be taken twice daily?

Losartan Dosing: Once-Daily vs. Twice-Daily Administration

Losartan should be administered once daily at a target dose of 100 mg according to FDA-approved labeling and clinical guidelines, though dividing the same total daily dose into twice-daily administration may be considered in specific situations. 1, 2

Standard Dosing Recommendations

• According to the 2020 ACC/AHA clinical performance and quality measures for adults with heart failure, the recommended target dose for losartan is 100 mg once daily 1
• The FDA-approved labeling for losartan specifically indicates once-daily dosing as the standard administration schedule 2
• Clinical pharmacokinetic studies support once-daily dosing, as losartan's active metabolite E3174 has a half-life of 6-9 hours, providing sustained 24-hour coverage 3

Evidence for Twice-Daily Dosing

• The FDA label acknowledges that twice-daily dosing at 50 mg to 100 mg/day gave consistently larger trough responses than once-daily dosing at the same total dose in hypertension studies 2
• Some ARBs in the same class, such as valsartan (160 mg twice daily) and quinapril (20 mg twice daily), are specifically recommended for twice-daily administration in heart failure guidelines 1
• A 2015 study found that twice-daily administration of losartan (50 mg twice daily) was more effective than once-daily evening dosing (100 mg) in eliminating non-dipper phenomenon in hypertensive patients 4

Recent Comparative Evidence

• A 2020 real-world effectiveness study comparing twice-daily versus once-daily losartan found no significant differences in blood pressure control between the two dosing regimens 5
• After propensity score adjustment, this study showed absolute differences in mean systolic BP ranging from -1.8 to 0.7 mmHg and diastolic BP ranging from -1.1 to 0.1 mmHg between twice-daily and once-daily regimens (all 95% confidence intervals crossed zero) 5
• This suggests that in real-world practice, twice-daily dosing offers no significant advantage over once-daily dosing for blood pressure control 5

Clinical Considerations for Dosing

• The HEAAL trial demonstrated that higher total daily doses of losartan (150 mg daily) were superior to lower doses (50 mg daily) in reducing heart failure hospitalizations, emphasizing the importance of achieving target doses rather than specific dosing frequency 1
• Guidelines emphasize titrating to maximally tolerated doses of ARBs to achieve optimal clinical outcomes in heart failure patients 1
• When initiating losartan therapy, doses should be adjusted no more frequently than every 2 weeks to reach target or maximally tolerated doses 1

Practical Recommendations

• For most patients, once-daily dosing of losartan at the target dose of 100 mg is recommended as the standard approach 1, 2
• Consider twice-daily dosing (50 mg twice daily) in patients with:
  • Significant blood pressure fluctuations throughout the day 4
  • Non-dipper hypertension pattern on ambulatory blood pressure monitoring 4
  • Inadequate 24-hour blood pressure control with once-daily dosing 2
• There is no evidence that twice-daily dosing improves clinical outcomes in terms of morbidity or mortality compared to once-daily dosing at the same total daily dose 5

Potential Pitfalls

• Dividing doses may reduce adherence due to increased dosing complexity 1
• Clinicians often underdose ARBs in clinical practice, failing to reach target doses that have been proven to reduce morbidity and mortality 1
• Focus should be on achieving the target total daily dose (100 mg) rather than on the frequency of administration 1