Is it acceptable to administer losartan (angiotensin II receptor antagonist) 100 mg twice a day to an adult patient with hypertension and no significant comorbidities?

Can Losartan Be Dosed at 100 mg Twice Daily?

No, losartan should not be dosed at 100 mg twice daily—the FDA-approved maximum dose is 100 mg once daily, and exceeding this provides no additional benefit while potentially increasing adverse effects. 1

FDA-Approved Dosing Parameters

• The maximum approved dose of losartan is 100 mg once daily for all indications including hypertension, left ventricular hypertrophy, and diabetic nephropathy 1
• The usual starting dose is 50 mg once daily, which can be increased to 100 mg once daily as needed to control blood pressure 1
• Clinical trials demonstrated that doses of 150 mg once daily gave no greater antihypertensive effect than 50-100 mg doses 1

Evidence Against Twice-Daily Dosing at 100 mg

• While twice-daily dosing at 50 mg (total 100 mg/day) gave consistently larger trough responses than 100 mg once daily, this does not justify exceeding the 100 mg total daily dose 1
• The trough-to-peak ratio for losartan ranges from 50-95% for systolic and 60-90% for diastolic responses, indicating sustained 24-hour efficacy with once-daily dosing 1
• Losartan and its active metabolite E3174 provide smooth 24-hour blood pressure control with once-daily administration 2, 3

Guideline-Recommended Dosing for Heart Failure

• For heart failure with reduced ejection fraction, ACC/AHA guidelines recommend losartan 100 mg once daily as the target dose, not 200 mg total daily 4
• The guidelines note that ACC/AHA actually recommends 150 mg as the target dose for heart failure, but because FDA labeling limits the maximum to 100 mg, the 100 mg once-daily dose is used in performance measures 4

What to Do If Blood Pressure Remains Uncontrolled

• Add a second antihypertensive agent rather than exceeding the maximum losartan dose 4
• The recommended combination is losartan plus a thiazide diuretic (hydrochlorothiazide 12.5-25 mg) or a calcium channel blocker (amlodipine 5-10 mg) 4, 5
• Adding hydrochlorothiazide 12.5 mg to losartan 50 mg once daily resulted in placebo-adjusted blood pressure reductions of 15.5/9.2 mmHg 1

Alternative ARB for Twice-Daily Dosing

• If twice-daily dosing is desired for an ARB, valsartan 160 mg twice daily (320 mg total daily) is the guideline-recommended option 4
• Valsartan has a shorter half-life than losartan, making twice-daily dosing more physiologically appropriate for this agent 4

Clinical Pharmacology Supporting Once-Daily Dosing

• Losartan's active metabolite E3174 has a terminal half-life of 6-9 hours and is 10-40 fold more potent than the parent compound 6
• The pharmacokinetics are linear and dose-proportional, with maximum blood pressure reductions occurring after approximately 50 mg doses 3, 6
• Studies using 24-hour ambulatory blood pressure monitoring confirmed sustained antihypertensive effect throughout 24 hours with once-daily dosing 7