What is the recommended dosage and usage of losartan (angiotensin II receptor antagonist) for a patient with hypertension or at risk of kidney damage due to diabetes?

Losartan Dosing and Usage for Hypertension and Diabetic Kidney Disease

For patients with hypertension and type 2 diabetes with nephropathy, start losartan at 50 mg once daily and titrate to 100 mg once daily based on blood pressure response to maximize renal protection. 1, 2

Standard Dosing Recommendations

Hypertension

• Starting dose: 50 mg once daily for most patients 2
• Maximum dose: 100 mg once daily 2
• Lower starting dose (25 mg): Use in patients with possible intravascular depletion (e.g., those on diuretic therapy) 2

Diabetic Nephropathy with Type 2 Diabetes

• Starting dose: 50 mg once daily 2
• Target dose: Increase to 100 mg once daily based on blood pressure response 1, 2
• The goal is to titrate to the highest approved dose tolerated, as renoprotective effects are dose-dependent 1

Hypertensive Patients with Left Ventricular Hypertrophy

• Start with 50 mg once daily 2
• Add hydrochlorothiazide 12.5 mg daily and/or increase losartan to 100 mg once daily 2
• May further increase hydrochlorothiazide to 25 mg once daily based on blood pressure response 2

Blood Pressure Targets

Target blood pressure <130/80 mmHg in patients with diabetes and chronic kidney disease. 1

• For most adult CKD patients, target systolic blood pressure <120 mmHg using standardized office measurement 1
• Multiple-drug therapy is generally required to achieve these targets 1

Monitoring Requirements

Check serum creatinine and potassium within 2-4 weeks after starting losartan or increasing the dose. 1, 3

Continue Losartan Unless:

• Serum creatinine rises by more than 30% within 4 weeks of initiation or dose increase 1
• Symptomatic hypotension develops 1
• Uncontrolled hyperkalemia persists despite medical management 1

Managing Hyperkalemia

• Halve the dose if potassium rises to >5.5 mmol/L 3
• Stop immediately if potassium rises to ≥6.0 mmol/L 3
• Hyperkalemia can often be managed by measures to reduce serum potassium rather than immediately stopping losartan 1

Clinical Evidence for Renal Protection

Losartan reduces the risk of doubling serum creatinine by 25% and end-stage renal disease by 28% in patients with type 2 diabetes and nephropathy. 4

• In the landmark RENAAL trial, losartan 50-100 mg daily reduced the composite endpoint of doubling serum creatinine, ESRD, or death by 16% compared to placebo (P=0.02) 4
• Losartan reduced proteinuria by 35% (P<0.001) 4
• These benefits exceeded those attributable to blood pressure changes alone 4

Special Populations

Hepatic Impairment

• Mild-to-moderate hepatic impairment: Start with 25 mg once daily 2
• Severe hepatic impairment: Not studied; use with extreme caution 2

Renal Impairment

• No dosage adjustment required for mild to moderate renal dysfunction 5
• Not removed by hemodialysis 6
• Consider starting at lower doses in patients with eGFR <45 mL/min/1.73 m² 3

Pediatric Patients (≥6 years)

• Starting dose: 0.7 mg/kg once daily (up to 50 mg total) 2
• Maximum: 1.4 mg/kg daily (not to exceed 100 mg) 2
• Not recommended in children <6 years or with eGFR <30 mL/min/1.73 m² 2

Critical Contraindications and Precautions

Never combine losartan with ACE inhibitors or direct renin inhibitors—this increases adverse effects without additional benefit. 1, 3

Absolute Contraindications:

• Pregnancy (second and third trimester associated with serious fetal toxicity) 1, 6
• Bilateral renal artery stenosis (risk of acute renal failure) 3
• Combination with ACE inhibitors, other ARBs, or direct renin inhibitors 1

Use with Caution:

• Avoid combining with potassium-sparing diuretics (e.g., spironolactone) due to compounded hyperkalemia risk 3
• Temporarily suspend during intercurrent illness, volume depletion, bowel preparation for colonoscopy, or prior to major surgery 1, 3

Combination Therapy

Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) if blood pressure remains uncontrolled on losartan alone. 1

• For blood pressure 140-159/90-99 mmHg: May start with single-drug therapy 1
• For blood pressure ≥160/100 mmHg: Start with two-drug combination 1
• Dihydropyridine calcium channel blockers are also appropriate add-on agents 1

Common Pitfalls to Avoid

• Using 50 mg as the final dose: Evidence suggests 100 mg daily provides superior renoprotection 7, 4
• Stopping losartan for modest creatinine increases: A 10-20% rise in creatinine is expected and hemodynamic, not indicative of kidney injury unless persistent 3
• Failing to restrict dietary sodium: Target sodium intake <2 g/day (<90 mmol/day) for synergistic effect with losartan 1, 3
• Not monitoring potassium in high-risk patients: Patients with CKD, diabetes, or on potassium-sparing medications require closer monitoring 3