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

Losartan Dosing for Hypertension and Diabetic Nephropathy

The recommended dosing of losartan for hypertension is 50 mg once daily initially, titrating to 100 mg once daily based on blood pressure response; for diabetic nephropathy, start with 50 mg once daily and increase to 100 mg once daily, as 100 mg provides superior renoprotection and blood pressure reduction. 1, 2

Adult Hypertension Dosing

• Initial dose: 50 mg once daily 2
• Maximum dose: 100 mg once daily 2
• Special populations:
  • Patients with possible intravascular depletion (e.g., on diuretic therapy): Start with 25 mg once daily 2
  • Mild-to-moderate hepatic impairment: Start with 25 mg once daily 2
  • Losartan is not recommended in severe hepatic impairment 2

Diabetic Nephropathy Dosing

• Initial dose: 50 mg once daily 2
• Target dose: 100 mg once daily 2
• Clinical evidence strongly supports using the 100 mg dose for optimal renoprotection 3
• The RENAAL trial demonstrated that losartan significantly reduced the incidence of doubling of serum creatinine, end-stage kidney disease, and death by 16% compared to placebo in patients with type 2 diabetes and chronic kidney disease 1, 4

Dose Optimization

• The American College of Cardiology recommends a minimum of at least 50% of the target dose (50 mg daily) for clinical benefit, with a target dose of 100 mg once daily 1
• Clinical studies have demonstrated that 100 mg daily is significantly more effective than 50 mg daily in reducing albuminuria (48% vs 30% reduction) and blood pressure in diabetic nephropathy 3
• Many clinicians use suboptimal doses of losartan (50 mg daily) when 100 mg daily provides greater benefits for both hypertension control and renoprotection 1

Monitoring Recommendations

• Check blood pressure 2-4 weeks after initiation or dose adjustment 1
• Monitor serum creatinine, eGFR, and potassium levels:
  • At baseline
  • At least annually
  • More frequently in patients with chronic kidney disease 1

Important Precautions

• Contraindications:
  • Pregnancy, particularly second and third trimesters (risk of fetal toxicity) 1, 5
  • Combination with ACE inhibitors or direct renin inhibitors (increased risk of adverse effects) 1
• Losartan is generally well-tolerated with minimal adverse effects 5, 6
• The pharmacokinetics are linear and dose-proportional, with no significant changes with repetitive administration 5

Combination Therapy

• For stage 2 hypertension (BP ≥160/100 mmHg), combination therapy with two antihypertensive agents of different classes is recommended 1
• Losartan can be combined with hydrochlorothiazide for enhanced blood pressure control 1, 2
• Fixed-dose combination of losartan with low-dose hydrochlorothiazide may provide additional antiproteinuric and blood pressure-lowering effects 1

Clinical Pearl

While the FDA label indicates that losartan can be administered once daily or by splitting the same total daily dose into two doses 5, most clinical guidelines and studies support once-daily dosing for improved adherence and similar efficacy 1, 3, 6.