What is the maximum recommended dose of losartan (angiotensin II receptor antagonist) for an adult patient with hypertension, considering factors such as impaired renal (kidney) function, hepatic impairment, diabetes, and geriatric status?

Maximum Dose of Losartan Potassium

The maximum FDA-approved dose of losartan is 100 mg once daily for hypertension, though ACC/AHA guidelines recommend 150 mg daily as the target dose for heart failure with reduced ejection fraction. 1, 2

Standard Maximum Dosing by Indication

Hypertension

• FDA-approved maximum: 100 mg once daily 1
• Starting dose: 50 mg once daily 1
• Can be increased to 100 mg once daily as needed for blood pressure control 1
• Patients with possible intravascular depletion (e.g., on diuretics) should start at 25 mg once daily 1

Heart Failure with Reduced Ejection Fraction

• ACC/AHA guideline target dose: 150 mg once daily 2
• However, the FDA-approved maximum remains 100 mg once daily 2, 1
• The 2020 ACC/AHA performance measures note this discrepancy explicitly, stating that while guidelines recommend 150 mg as the target dose, current FDA labeling limits the maximum to 100 mg 2
• Evidence from the HEAAL trial demonstrated that 150 mg daily was superior to 50 mg daily, with a 10% relative risk reduction in death or heart failure hospitalization 2

Nephropathy in Type 2 Diabetes

• Maximum dose: 100 mg once daily 1
• Starting dose: 50 mg once daily 1
• Should be increased to 100 mg once daily based on blood pressure response 1

Special Population Adjustments

Hepatic Impairment

• Mild-to-moderate hepatic impairment: Start at 25 mg once daily 1
• Maximum dose should be carefully titrated based on response 1
• Losartan has not been studied in severe hepatic impairment and should be avoided 1

Renal Impairment

• No dose adjustment required for various degrees of renal insufficiency 3
• Losartan is not removed during hemodialysis 3
• The same maximum doses apply regardless of renal function 1

Pediatric Patients (6-16 years)

• Maximum: 1.4 mg/kg once daily (not to exceed 100 mg total) 1
• Usual starting dose: 0.7 mg/kg once daily (up to 50 mg total) 1
• Not recommended in children <6 years or with eGFR <30 mL/min/1.73 m² 1

Geriatric Patients

• No dose adjustment necessary based on age alone 3
• The same maximum doses apply as for younger adults 1

Clinical Context and Dosing Considerations

Evidence for Higher Doses

The discrepancy between FDA labeling (100 mg maximum) and guideline recommendations (150 mg target for heart failure) stems from trial evidence showing dose-dependent benefits 2, 4:

• The ELITE II trial showed that losartan 50 mg daily was insufficient compared to captopril 2
• The HEAAL trial demonstrated superiority of 150 mg daily over 50 mg daily 2
• These findings parallel the ATLAS trial with lisinopril, indicating greater benefit from higher doses of renin-angiotensin system blockers 2

Practical Prescribing Guidance

• For hypertension: Titrate to 100 mg once daily (FDA maximum) 1, 2
• For heart failure: Target 100 mg once daily per FDA labeling, though guidelines suggest 150 mg would be optimal 2, 1
• Doses above 100 mg daily remain off-label in the United States despite guideline support 2

Monitoring Requirements

When using maximum doses, monitor 5, 6:

• Blood pressure within 2-4 weeks of dose increases 5
• Serum creatinine and potassium within 2-4 weeks 5, 6
• Continue therapy unless creatinine rises >30% within 4 weeks 5, 6

Common Pitfalls

• Using 50 mg as the final dose: This is often insufficient; most patients benefit from titration to 100 mg daily 2, 4
• Combining with ACE inhibitors or direct renin inhibitors: This increases adverse events without additional benefit and should be avoided 2, 6
• Discontinuing due to mild creatinine elevation: Small increases (<30%) are expected and acceptable 5, 6
• Pregnancy: Losartan is absolutely contraindicated in pregnancy (all trimesters) 2, 3