Is increasing losartan (angiotensin II receptor antagonist) to 50 mg twice daily (bid) more effective than 100 mg once daily for blood pressure control?

Losartan Dosing: 100 mg Once Daily vs. 50 mg Twice Daily

For optimal blood pressure control, losartan 100 mg once daily is preferred over 50 mg twice daily, as this is the FDA-approved target dose that provides effective 24-hour coverage while promoting medication adherence. 1, 2

Evidence-Based Dosing Recommendations

The FDA-approved target dose for losartan in hypertension is 100 mg once daily 2. This is supported by clinical guidelines that specifically identify 100 mg once daily as the target dose for losartan 1. The 2020 ACC/AHA guidelines provide a clear table of target doses for angiotensin receptor blockers (ARBs), listing losartan at 100 mg once daily as the recommended target dose.

Efficacy of Once-Daily vs. Twice-Daily Dosing

While the FDA label notes 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 2, several factors favor the once-daily approach:

1. Medication adherence: Once-daily dosing improves adherence compared to twice-daily regimens 3
2. Sufficient coverage: The 100 mg once-daily dose provides adequate 24-hour blood pressure control 2
3. Guideline concordance: Major cardiology societies recommend the 100 mg once-daily target dose 1

Pharmacokinetic Considerations

Losartan is rapidly absorbed after oral administration, reaching maximum concentrations in 1-2 hours 4. It is converted to an active metabolite (E3174) that has a longer half-life (6-9 hours) and is 10-40 times more potent than losartan itself 4. This active metabolite contributes significantly to the 24-hour efficacy of once-daily dosing.

Clinical Trial Evidence

Clinical trials have demonstrated that:

• Doses of 50 mg, 100 mg, and 150 mg once daily provided statistically significant decreases in blood pressure compared to placebo 2
• The 150 mg dose did not provide greater effect than 50-100 mg 2
• The HEAAL trial showed that 150 mg daily of losartan was superior to 50 mg daily, supporting the use of higher doses when tolerated 1, 3

Special Considerations

• Resistant hypertension: If blood pressure remains uncontrolled on 100 mg daily, adding a thiazide diuretic, calcium channel blocker, or other agent is preferred over splitting the dose 3
• Renal impairment: No dosage adjustment is necessary for patients with renal insufficiency 4
• Hepatic impairment: No dosage adjustment is needed for mild hepatic impairment 4

Practical Implementation

1. Start with losartan 50 mg once daily
2. If blood pressure is not controlled after 2-4 weeks, increase to 100 mg once daily
3. If blood pressure remains uncontrolled on 100 mg once daily, add a second agent (preferably a thiazide diuretic or calcium channel blocker) rather than splitting the dose 3
4. Monitor blood pressure, renal function, and potassium levels regularly

Common Pitfalls to Avoid

• Underdosing: Failing to titrate to the target dose of 100 mg daily when tolerated
• Unnecessary dose splitting: Dividing the dose when once-daily administration is effective and promotes better adherence
• Overlooking combination therapy: Adding a second agent may be more effective than dose manipulation when blood pressure is not controlled on 100 mg daily

In conclusion, while twice-daily dosing may provide slightly better trough responses in some patients, the clinical benefits of improved adherence with once-daily dosing, combined with the established efficacy of the 100 mg once-daily dose, make this the preferred approach for most patients with hypertension.