Should losartan be taken once daily or twice daily?

Losartan Dosing Frequency

Losartan should be taken once daily for most patients with hypertension, heart failure, or diabetic nephropathy, with the option to split the total daily dose into twice-daily administration if more consistent 24-hour blood pressure control is needed. 1, 2

Standard Dosing Recommendations

Hypertension

• The FDA-approved dosing for hypertension is 50 mg once daily as the starting dose, with titration to a maximum of 100 mg once daily as needed for blood pressure control. 2
• The American College of Cardiology/American Heart Association guidelines explicitly state that losartan can be administered with a daily frequency of "1 or 2", meaning both once-daily and twice-daily dosing are acceptable for the 50-100 mg/day dose range. 1
• If twice-daily dosing is desired for more consistent 24-hour coverage, split the 100 mg total daily dose into 50 mg twice daily. 1

Heart Failure with Reduced Ejection Fraction

• The target dose is 100-150 mg once daily, with the HEAAL trial demonstrating that 150 mg daily was superior to 50 mg daily (10% relative risk reduction in death or heart failure hospitalization, P=0.027). 1
• The American College of Cardiology recommends 100 mg once daily as the target dose for heart failure patients. 1

Diabetic Nephropathy

• The recommended target dose is 100 mg once daily, based on the RENAAL trial which demonstrated a 20% reduction in the primary composite renal outcome. 1
• The KDOQI guidelines list losartan dosing for diabetic kidney disease as 25-100 mg daily in 1-2 divided doses, not exceeding 100 mg total. 1

Pharmacokinetic Rationale

• Losartan's active metabolite E3174 has an estimated terminal half-life of 6-9 hours, which supports once-daily dosing for most patients. 3
• Clinical studies using 24-hour ambulatory blood pressure monitoring demonstrate that losartan 50-100 mg once daily produces a smooth, sustained antihypertensive effect throughout the 24-hour dosing interval. 4
• The trough-to-peak ratio for losartan is 0.91 for systolic blood pressure and 1.14 for diastolic blood pressure, indicating adequate 24-hour coverage with once-daily dosing. 5

When to Consider Twice-Daily Dosing

Split the total daily dose into twice-daily administration (e.g., 50 mg every 12 hours for a total of 100 mg/day) when:

• More uniform blood pressure control throughout the day is needed, particularly if morning hypertension persists despite once-daily dosing. 1
• The patient experiences end-of-dose blood pressure elevation before the next scheduled dose. 1

Critical Safety Considerations

• Monitor serum creatinine and potassium within 1-2 weeks after initiating therapy or increasing doses, especially in patients with chronic kidney disease, diabetes, or those receiving potassium-sparing agents. 1
• Never combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren), as dual RAAS blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2-3-fold without cardiovascular benefit. 1
• Losartan is absolutely contraindicated in pregnancy due to serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death). 1

Common Pitfalls to Avoid

• Do not exceed 100 mg daily for hypertension, even when splitting into twice-daily doses; the maximum FDA-approved dose for hypertension is 100 mg total per day. 2
• Avoid underdosing: Less than 25% of patients are titrated to target doses in clinical practice, yet higher doses provide significantly better cardiovascular outcomes than lower doses. 1
• If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5-25 mg daily rather than exceeding the maximum losartan dose or switching to twice-daily dosing. 1