What is the recommended dose of losartan (angiotensin II receptor antagonist) for treating hypertension and diabetic nephropathy?

Losartan Dosing for Hypertension and Diabetic Nephropathy

For hypertension, start losartan at 50 mg once daily and increase to 100 mg once daily as needed for blood pressure control; for diabetic nephropathy, start at 50 mg once daily and titrate to 100 mg once daily, which is the maximum approved dose that provides optimal renoprotection. 1

Standard Dosing by Indication

Hypertension

• Start with 50 mg once daily as the usual initial dose for most adults 1
• Titrate to 100 mg once daily if blood pressure remains uncontrolled 1
• For patients with possible intravascular depletion (e.g., on diuretic therapy), start with 25 mg once daily 1
• The 100 mg once daily dose represents the maximum recommended dose for hypertension 1

Diabetic Nephropathy

• Start with 50 mg once daily and increase to 100 mg once daily based on blood pressure response 1
• The 100 mg daily dose is optimal for renoprotection, providing significantly greater reduction in albuminuria (48% reduction) compared to 50 mg daily (30% reduction) 2
• The landmark RENAAL trial demonstrated that losartan 100 mg daily significantly reduced doubling of serum creatinine, end-stage kidney disease, and death by 16% each compared to placebo 3

Critical Titration Principles

KDIGO 2020 guidelines strongly recommend titrating ARBs to the highest approved dose that is tolerated in patients with diabetes, hypertension, and albuminuria 3. This recommendation is based on:

• Dose-dependent renoprotective effects independent of blood pressure lowering 3
• Research showing 100 mg daily is significantly more effective than 50 mg daily for both albuminuria reduction and blood pressure control without additional benefit from 150 mg 2
• The maximum FDA-approved dose is 100 mg daily for all indications 1

Special Populations

Hepatic Impairment

• Start with 25 mg once daily in patients with mild-to-moderate hepatic impairment 1
• Losartan has not been studied in severe hepatic impairment 1

Renal Impairment

• No dose adjustment needed for various degrees of renal insufficiency, including patients on hemodialysis 1, 4
• Losartan is effective and well-tolerated at 50-100 mg daily in patients with chronic kidney disease and eGFR >30 mL/min per 1.73 m² 4

Pediatric Patients (≥6 years)

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

Combination Therapy Considerations

If blood pressure remains uncontrolled on losartan 100 mg daily:

• Add hydrochlorothiazide 12.5-25 mg daily 1
• Consider adding a dihydropyridine calcium channel blocker or thiazide-like diuretic 3

Critical contraindication: Never combine losartan with ACE inhibitors or direct renin inhibitors, as this increases risk of hyperkalemia and renal dysfunction 3, 5

Monitoring Requirements

Monitor serum creatinine/eGFR and potassium levels:

• Within 1-2 weeks after initiating therapy 5
• At least annually during maintenance therapy 3
• More frequently in patients with baseline renal impairment or those on diuretics 3

Common Pitfalls to Avoid

Underdosing is widespread in clinical practice, with less than 25% of patients ever titrated to target doses 5. To optimize outcomes:

• Do not stop at 50 mg daily if the patient tolerates it well and has diabetes with albuminuria—the evidence clearly shows 100 mg provides superior renoprotection 2
• Titrate gradually over 2-4 weeks to assess tolerance and avoid hypotension 5
• Do not exceed 100 mg daily—doses above this have not shown additional benefit and are not FDA-approved 1, 2
• The pharmacokinetics are linear and dose-proportional, with the active metabolite E-3174 having a half-life of 6-9 hours, supporting once-daily dosing 6