What is the maximum recommended dose of losartan (angiotensin II receptor antagonist) for a patient with hypertension or diabetic nephropathy?

Maximum Recommended Dose of Losartan

The maximum recommended dose of losartan is 100 mg once daily for hypertension, and this same 100 mg daily dose represents the target for optimal renoprotection in diabetic nephropathy and chronic kidney disease. 1

Standard Maximum Dosing by Indication

Hypertension

• The FDA-approved maximum dose is 100 mg once daily 1
• The usual starting dose is 50 mg once daily, which can be increased to 100 mg once daily as needed for blood pressure control 1
• The 2017 ACC/AHA hypertension guidelines confirm the usual dose range as 50-100 mg/day with a frequency of 1 or 2 times daily 2
• If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5-25 mg daily rather than exceeding the 100 mg losartan dose 3

Diabetic Nephropathy and CKD

• Start at 50 mg once daily and titrate to 100 mg once daily for maximum renoprotective benefit 1
• Clinical trials demonstrating kidney protection (RENAAL study) used the 100 mg daily dose, not lower doses 4, 5
• Research demonstrates that 100 mg daily is significantly more effective than 50 mg daily in reducing albuminuria (48% vs 30% reduction, p<0.01) and blood pressure 6
• The target dose of 100 mg once daily provides optimal renoprotection according to ACC and ESC guidelines 4

Important Dosing Considerations

Once vs Twice Daily Administration

• Both once-daily (100 mg) and twice-daily (50 mg BID) administration are acceptable and guideline-supported 3
• The total daily dose should not exceed 100 mg regardless of dosing frequency 3
• Once-daily dosing of the full 100 mg is more commonly recommended for convenience 3

Special Populations Requiring Lower Starting Doses

• Hepatic impairment (mild-to-moderate): Start at 25 mg once daily 1
• Volume depletion (e.g., on diuretic therapy): Start at 25 mg once daily 1
• Pediatric patients: Maximum 1.4 mg/kg daily (not to exceed 100 mg total) 1

Critical Safety Monitoring

Monitoring Parameters

• Check serum creatinine/eGFR and potassium within 1-2 weeks after initiation or dose increase 4, 7
• Accept up to 30% increase in serum creatinine within 4 weeks as expected hemodynamic effect 4
• Monitor for symptomatic hypotension, especially when titrating to higher doses 4

Hyperkalemia Management

• Monitor potassium levels closely, particularly in patients with CKD (eGFR <45 mL/min/1.73 m²), diabetes, or those on potassium-sparing agents 2, 7
• Manage hyperkalemia with potassium-lowering measures rather than stopping losartan when possible 4
• Halve the dose if potassium rises to >5.5 mmol/L; stop if ≥6.0 mmol/L 7

Common Pitfalls to Avoid

Underdosing

• Don't underdose: The proven renoprotective benefits in clinical trials were achieved with 100 mg daily, not lower doses 4, 6
• Less than 25% of patients in clinical practice are ever titrated to target doses, representing widespread underdosing 3
• The 50 mg dose provides inferior outcomes compared to 100 mg for both blood pressure control and renoprotection 6

Inappropriate Combination Therapy

• Never combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren) due to increased risk of hyperkalemia, syncope, and acute kidney injury without additional benefit 2, 3, 7
• Avoid simultaneous use with ACE inhibitors and aldosterone antagonists due to compounded hyperkalemia risk 3

Premature Discontinuation

• Don't stop losartan for mild creatinine increases (<30%): this is expected and hemodynamic, not indicative of kidney injury 4
• Continue losartan even when eGFR falls below 30 mL/min/1.73 m², unless symptomatic hypotension or uncontrolled hyperkalemia develops 4

Note on Higher Doses (150 mg)

While some evidence suggests potential benefit of 150 mg daily in heart failure with reduced ejection fraction (HEAAL trial showed 10% relative risk reduction vs 50 mg, p=0.027) 3, this exceeds the FDA-approved maximum dose of 100 mg daily 1. The 150 mg dose is not FDA-approved for any indication and should not be used in routine clinical practice for hypertension or diabetic nephropathy 1.