Losartan Dosing for Hypertension: 100 mg Once Daily vs 50 mg Twice Daily
For a 66-year-old patient with essential hypertension on indapamide 2.5 mg, losartan 100 mg once daily is the preferred dosing regimen over 50 mg twice daily, as it provides equivalent or superior blood pressure control with better adherence and is the FDA-approved standard dosing approach. 1
Evidence Supporting Once-Daily 100 mg Dosing
The FDA label explicitly states that doses of 50 mg, 100 mg, and 150 mg once daily produced statistically significant blood pressure reductions of 5.5 to 10.5/3.5 to 7.5 mmHg compared to placebo, with the 150 mg dose providing no greater effect than 50-100 mg. 1
Clinical trials demonstrated that twice-daily dosing at 50-100 mg/day gave consistently larger trough responses than once-daily dosing at the same total dose, with trough-to-peak ratios for systolic and diastolic responses of 50-95% and 60-90% respectively. 1
However, the practical advantage of once-daily dosing for medication adherence outweighs the modest pharmacokinetic benefit of twice-daily administration, particularly in elderly patients where adherence is critical for long-term blood pressure control. 1, 2
Pharmacokinetic Considerations
Losartan's active metabolite E-3174 has an estimated terminal half-life of 6-9 hours and is 10-40 fold more potent than the parent compound, providing sustained antihypertensive effects throughout the 24-hour dosing interval. 2
The pharmacokinetics of losartan and E-3174 are linear and dose-proportional, and do not substantially change with repetitive administration, supporting once-daily dosing at higher doses rather than split dosing. 2
Losartan demonstrates a smooth, gradual onset of action and does not affect normal circadian variations in blood pressure, making once-daily dosing physiologically appropriate. 3
Clinical Trial Evidence
Ambulatory 24-hour blood pressure monitoring studies confirmed that losartan 50 mg or 100 mg once daily exerted sustained antihypertensive effects throughout the entire 24-hour period. 3
The maximum recommended daily dose of losartan is 100 mg, which can be given as a once-daily dose or by splitting the same total daily dose into two doses, though once-daily administration is standard practice. 2
In the LIFE study, patients were randomized to losartan 50 mg once daily, with uptitration to 100 mg once daily if blood pressure targets were not achieved, demonstrating the guideline-endorsed approach of once-daily dosing. 1
Combination Therapy Considerations
For this patient already on indapamide 2.5 mg, adding losartan 50 mg once daily with uptitration to 100 mg once daily if needed follows the standard treatment algorithm. 1
The addition of hydrochlorothiazide 12.5 mg to losartan 50 mg once daily resulted in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg, suggesting that combination therapy with the existing indapamide may provide substantial benefit. 1
If blood pressure remains uncontrolled on losartan 100 mg plus indapamide 2.5 mg, adding a calcium channel blocker as the third agent is recommended rather than splitting the losartan dose. 4
Practical Implementation
Start with losartan 50 mg once daily and reassess blood pressure within 2-4 weeks, as most antihypertensive effect is apparent within 2 weeks with maximal reduction at 4 weeks. 1
If blood pressure target (<140/90 mmHg minimum, ideally <130/80 mmHg) is not achieved, increase to losartan 100 mg once daily before adding a third agent. 4, 1
No dosage adjustment is necessary based on age, sex, race, or mild hepatic impairment, making 100 mg once daily appropriate for this 66-year-old patient. 2