Losartan Dosing for Hypertension
Losartan can be given twice daily for hypertension when once-daily dosing does not provide adequate 24-hour blood pressure control, though once-daily dosing is the standard initial approach.
Standard Dosing Recommendations
- Initial dosing: Losartan is typically initiated at 50 mg once daily for hypertension 1
- Dose titration: Can be increased to 100 mg once daily if blood pressure control is inadequate 2
- Twice-daily option: When 24-hour blood pressure control is insufficient with once-daily dosing, dividing the total daily dose into twice-daily administration is appropriate
Evidence Supporting Twice-Daily Dosing
Research studies have evaluated various losartan dosing regimens:
- A multicenter, double-blind trial compared losartan 50 mg once daily, 50 mg twice daily, and 100 mg once daily, finding that all regimens significantly decreased mean 24-hour ambulatory blood pressure compared to placebo 3
- The twice-daily regimen may provide more consistent 24-hour blood pressure control in some patients, particularly those who experience blood pressure elevations toward the end of the once-daily dosing interval
Pharmacokinetic Considerations
Losartan's active metabolite E-3174 has a longer half-life than the parent compound and contributes substantially to its antihypertensive effect:
- Losartan itself has a relatively short half-life (1-2 hours)
- E-3174 (active metabolite) has a longer half-life (6-9 hours), which contributes to the extended duration of action 4, 5
- For some patients, particularly those with faster metabolism or those who experience "wear-off" effects before the next dose, twice-daily dosing may provide more consistent angiotensin II receptor blockade
Clinical Application
When considering twice-daily dosing:
- Evaluate 24-hour blood pressure control: Use ambulatory or home blood pressure monitoring to identify patients with inadequate control in the last few hours of the dosing interval
- Dosing adjustment: When switching to twice-daily dosing, the total daily dose should typically be divided (e.g., 50 mg twice daily instead of 100 mg once daily)
- Monitoring: After changing to twice-daily dosing, reassess blood pressure control and adjust as needed
Special Populations
- Renal impairment: No dosage adjustment is required for mild to moderate renal dysfunction, regardless of once or twice-daily dosing 6
- Elderly patients: No initial dosage adjustment is necessary based on age alone 4
Combination Therapy Considerations
- If blood pressure remains uncontrolled despite optimized losartan dosing (either once or twice daily), adding a thiazide diuretic is recommended rather than continuing to increase losartan dose 2, 1
- The 2024 ESC guidelines recommend initial combination therapy with an ARB (like losartan) plus either a thiazide diuretic or calcium channel blocker for most patients with stage 2 hypertension 2
While twice-daily dosing of losartan is not specifically mentioned in most major hypertension guidelines, it represents a clinically reasonable approach for patients who demonstrate inadequate 24-hour blood pressure control with once-daily dosing, particularly toward the end of the dosing interval.