Can Losartan (angiotensin II receptor antagonist) 100mg be prescribed twice a day?

Losartan 100mg Twice Daily Dosing

Losartan 100mg should not be prescribed twice daily as the FDA-approved maximum daily dose is 100mg once daily for hypertension, with no evidence supporting twice-daily dosing at this maximum strength. 1

FDA-Approved Dosing Guidelines

• The FDA-approved maximum dose of losartan for hypertension is 100mg once daily 1
• For hypertension, the usual starting dose is 50mg once daily, which can be increased to a maximum of 100mg once daily as needed to control blood pressure 1
• For nephropathy in Type 2 diabetic patients, the usual starting dose is 50mg once daily, with potential increase to 100mg once daily based on blood pressure response 1

Evidence from Clinical Guidelines

• According to the ACC/AHA guidelines, losartan can be administered once or twice daily, but the total daily dose should not exceed 100mg 2
• The ACC/AHA hypertension guidelines specifically list losartan's usual dose range as 50-100mg/day with a daily frequency of "1 or 2" 2
• While twice-daily dosing at 50mg per dose (100mg total daily) may provide more consistent trough responses than once-daily dosing at the same total dose, exceeding 100mg total daily is not recommended 1

Special Considerations for Heart Failure

• For heart failure patients with reduced ejection fraction, the target dose of losartan is 100mg once daily 3
• The HEAAL trial demonstrated that 150mg daily of losartan (as a single dose) was superior to 50mg daily for heart failure outcomes, but this higher dosing is not FDA-approved in the US 3
• European guidelines recommend losartan 50mg as the starting dose with 150mg as the target dose for patients with heart failure 3

Pharmacokinetic Considerations

• Losartan has a relatively short half-life, but its active metabolite E3174 has a longer half-life of 6-9 hours, providing sustained therapeutic effect 4
• Studies show that the trough-to-peak ratio for systolic and diastolic responses is 50-95% and 60-90% respectively, supporting once-daily dosing 1
• A special sustained-release formulation (Losartan Cronos) has been developed specifically to provide 24-hour coverage with once-daily dosing 5

Safety Concerns with Higher Dosing

• Exceeding FDA-approved dosing may increase the risk of adverse effects such as hypotension, especially in patients with volume depletion 1
• Dizziness is the most common adverse effect reported with losartan, occurring more frequently than with placebo 6, 7
• Monitoring for hyperkalemia is important, especially when using higher doses of losartan 2

Clinical Approach

• If better blood pressure control is needed:
  • Ensure patient is taking the maximum FDA-approved dose of 100mg once daily 1
  • Consider adding a thiazide diuretic (e.g., hydrochlorothiazide 12.5-25mg) which provides additive blood pressure-lowering effects 2, 8
  • If twice-daily dosing is desired for more consistent coverage, split the 100mg total daily dose into 50mg twice daily 2
  • Consider alternative antihypertensive agents from different classes if blood pressure remains uncontrolled on maximum losartan dose plus a diuretic 2

Common Pitfalls to Avoid

• Exceeding the FDA-approved maximum daily dose of 100mg may increase adverse effects without providing proportional additional benefit 1
• Combining losartan with ACE inhibitors should be avoided due to increased risk of hyperkalemia and renal dysfunction 3
• Patients with hepatic impairment require lower dosing (starting at 25mg once daily) 1
• Losartan should be avoided in pregnancy due to risk of fetal toxicity 4