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

Losartan Dosing for Adults with Hypertension and Diabetic Nephropathy

For adults with hypertension and diabetic nephropathy, losartan should be initiated at 50 mg once daily and titrated to 100 mg once daily based on blood pressure response, as this higher dose provides optimal renoprotection. 1

Initial Dosing and Titration

• Starting dose: 50 mg once daily 1
• Target dose: 100 mg once daily 1, 2
• Special populations:
  • For patients with possible intravascular depletion (e.g., on diuretic therapy): Start with 25 mg once daily 1
  • For patients with mild-to-moderate hepatic impairment: Start with 25 mg once daily 1
  • Not recommended for patients with severe hepatic impairment 1

Evidence for Optimal Dosing in Diabetic Nephropathy

The FDA label specifically recommends titrating to 100 mg once daily for diabetic nephropathy patients based on blood pressure response 1. This recommendation is supported by strong evidence from landmark clinical trials:

• The RENAAL trial demonstrated that losartan significantly reduced the incidence of doubling of serum creatinine, end-stage kidney disease, and death by 16% compared with placebo in patients with type 2 diabetes and chronic kidney disease 3

• Dose-dependent renoprotection has been demonstrated in clinical studies, with higher doses providing greater albuminuria reduction 3, 4

• A dedicated study on optimal losartan dosing found that 100 mg daily was significantly more effective than 50 mg daily in reducing albuminuria (48% vs 30% reduction) and blood pressure in diabetic nephropathy patients 4

Monitoring Recommendations

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

Important Considerations and Precautions

• Pregnancy: Losartan is contraindicated during pregnancy, particularly in the second and third trimesters, due to risk of fetal toxicity 2, 5

• Combination therapy:

  • Avoid combining losartan with ACE inhibitors or direct renin inhibitors as this increases adverse effects without providing additional benefits 2
  • For resistant hypertension, losartan can be combined with a diuretic and other antihypertensive agents 2
  • Fixed-dose combination of losartan with low-dose hydrochlorothiazide may provide additional antiproteinuric and blood pressure-lowering effects in patients not achieving target blood pressure with losartan alone 6

• Common side effects: Generally well-tolerated with minimal serious adverse events (reported in only 0.2% of patients in one large study) 7

Clinical Pearl

While many clinicians use suboptimal doses of losartan (50 mg daily), the evidence clearly supports using 100 mg daily for greater benefits in both hypertension control and renoprotection in diabetic nephropathy patients 2, 4. The higher dose should be targeted whenever possible, as it provides significantly better outcomes without substantially increasing adverse effects.