What is the recommended dosage and use of Losartan (Angiotensin II Receptor Blocker) for treating Hypertension (High Blood Pressure) and Diabetic Nephropathy (Kidney Damage due to Diabetes)?

Losartan Dosage and Use for Hypertension and Diabetic Nephropathy

For patients with hypertension and diabetic nephropathy, losartan should be initiated at 50 mg once daily and titrated to 100 mg once daily to maximize renoprotective effects and blood pressure control. 1, 2

Dosing for Hypertension

• Initial dose: 50 mg once daily for most adult patients 1
• Maximum dose: Can be increased to 100 mg once daily as needed to control blood pressure 1
• Special populations: A starting dose of 25 mg is recommended for patients with possible intravascular depletion (e.g., those on diuretic therapy) 1
• Hepatic impairment: For patients with mild-to-moderate hepatic impairment, start with 25 mg once daily; losartan has not been studied in severe hepatic impairment 1

Dosing for Diabetic Nephropathy

• Initial dose: 50 mg once daily 1
• Titration: Increase to 100 mg once daily based on blood pressure response 1
• Optimal dose: Evidence suggests 100 mg daily provides optimal renoprotection, with significantly greater reduction in albuminuria compared to 50 mg (48% vs 30% reduction) 3

Mechanism and Benefits

For Hypertension:

• Losartan effectively reduces systolic/diastolic blood pressure by 5.5-10.5/3.5-7.5 mmHg compared to placebo 1
• Addition of low-dose hydrochlorothiazide (12.5 mg) to losartan 50 mg once daily results in further blood pressure reductions of 15.5/9.2 mmHg 1

For Diabetic Nephropathy:

• As an ARB, losartan blocks the renin-angiotensin system, providing renoprotection by reducing intraglomerular pressure 2
• Losartan reduces the risk of progression to severely increased albuminuria by 55% (RR: 0.45; 95% CI: 0.35-0.57) 2
• Reduces the risk of doubling of serum creatinine by 16% (RR: 0.84; 95% CI: 0.72-0.98) 2
• In the RENAAL study, losartan reduced the incidence of end-stage renal disease by 28% (p=0.002) and doubling of serum creatinine by 25% (p=0.006) compared to placebo 4
• Reduces proteinuria by approximately 35% (p<0.001) 4

Clinical Application Guidelines

• Initiation: Start with low dose and titrate to the highest approved dose that is tolerated 2
• Monitoring: Regular monitoring of kidney function and serum potassium is necessary 2
• Blood pressure target: Aim for a target blood pressure of less than 120/80 mmHg in patients with CKD 2
• Combination therapy: Most patients will require combination therapy to achieve target blood pressure; however, avoid combining ARBs with ACE inhibitors or direct renin inhibitors 2

Important Considerations and Precautions

• Dual RAS blockade: Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor therapy as this increases risk of acute kidney injury and hyperkalemia without additional benefit for cardiovascular outcomes or CKD progression 2
• Dose-dependent effects: The renoprotective effect of losartan is dose-dependent, with higher doses providing greater protection 3
• Hyperkalemia risk: Monitor serum potassium levels regularly, especially in patients with reduced kidney function 2
• Acute kidney injury risk: Monitor kidney function after initiation, particularly in patients at risk of volume depletion 2

Patient Selection

• Strongest indication: Patients with diabetes, hypertension, and albuminuria (categories A2 and A3) have the strongest recommendation for ARB therapy (1B recommendation) 2
• Non-diabetic CKD: ARBs are also recommended for non-diabetic patients with hypertension and severely increased albuminuria (1B recommendation) 2
• Moderate albuminuria without diabetes: ARBs are suggested for patients with hypertension, CKD, and moderately increased albuminuria without diabetes (2C recommendation) 2