What is the recommended dosage and use of Losartan (angiotensin II receptor blocker) for treating high blood pressure and protecting kidneys from damage due to diabetes?

Losartan for Hypertension and Diabetic Nephropathy

For patients with diabetes, hypertension, and albuminuria, losartan should be initiated at 50 mg once daily and titrated to 100 mg once daily—the optimal dose for both blood pressure control and kidney protection. 1, 2

Indications and Patient Selection

Losartan is specifically indicated for patients with diabetes, hypertension, and albuminuria to slow progression of chronic kidney disease and reduce cardiovascular events. 1

• The RENAAL trial demonstrated that losartan 100 mg daily reduced doubling of serum creatinine by 16%, end-stage renal disease by 28%, and death by 16% in patients with type 2 diabetes and nephropathy (albuminuria >1 g/day). 1
• These renoprotective effects occurred independent of blood pressure reduction, indicating direct kidney-protective mechanisms beyond antihypertensive action. 1
• In hypertensive diabetic patients with left ventricular hypertrophy, losartan reduced cardiovascular mortality by 37% and total mortality by 39% compared to atenolol. 3

Dosing Strategy

Start with losartan 50 mg once daily, then increase to 100 mg once daily based on blood pressure response and tolerability. 2

Standard Dosing Protocol:

• Initial dose: 50 mg once daily for most patients 2
• Target dose: 100 mg once daily for diabetic nephropathy 2, 4
• Maximum dose: 100 mg once daily (doses above this provide no additional benefit) 2
• Reduced starting dose: 25 mg once daily for patients with possible intravascular depletion (e.g., on diuretic therapy) or mild-to-moderate hepatic impairment 2

Evidence for Dose Selection:

• Research in type 1 diabetic patients with nephropathy showed losartan 100 mg daily reduced albuminuria by 48% compared to 30% with 50 mg daily, demonstrating clear dose-dependent renoprotection. 4
• Losartan 100 mg daily was significantly more effective than 50 mg daily in reducing both albuminuria (P<0.01) and blood pressure (P=0.05), while 150 mg provided no additional benefit over 100 mg. 4
• The FDA-approved maximum dose for diabetic nephropathy is 100 mg once daily. 2

Titration and Monitoring Algorithm

Titrate losartan to the highest approved dose tolerated (up to 100 mg daily) to maximize kidney protection. 1

Monitoring Schedule:

1. Baseline: Measure blood pressure, serum creatinine/eGFR, serum potassium, and albumin-to-creatinine ratio 1, 5

2. Within 2-4 weeks after initiation or dose increase: Check blood pressure, serum creatinine, and serum potassium 1

3. Continue therapy if:

   • Serum creatinine rises <30% from baseline 1
   • Potassium remains <5.5 mEq/L (manageable hyperkalemia) 1
   • No symptomatic hypotension 1

4. Discontinue or reduce dose if:

   • Serum creatinine rises >30% within 4 weeks of initiation or dose increase 1
   • Uncontrolled hyperkalemia despite medical management 1
   • Symptomatic hypotension 1

5. Annual monitoring: Serum creatinine/eGFR, potassium, blood pressure, and albuminuria 5

Management of Common Adverse Effects

Hyperkalemia Management:

Do not immediately discontinue losartan for hyperkalemia—first attempt medical management to preserve renoprotective benefits. 1

• Review and discontinue potassium supplements and potassium-sparing diuretics 1
• Moderate dietary potassium intake 1
• Correct volume depletion 1
• Consider potassium binders if needed 1
• Only reduce dose or discontinue if hyperkalemia remains uncontrolled despite these measures 1

Acute Kidney Injury Considerations:

• Counsel patients to temporarily hold losartan during acute illness with vomiting or diarrhea (risk of volume depletion) 5
• Review for bilateral renal artery stenosis if creatinine rises >30% 1
• Reassess concomitant medications (NSAIDs, diuretics) that may contribute to AKI 1

Critical Contraindications and Warnings

Never combine losartan with an ACE inhibitor or direct renin inhibitor—this dual blockade increases risks of hypotension, hyperkalemia, and acute renal failure without added benefit. 1, 5

• Avoid in pregnancy—discontinue immediately if pregnancy occurs or is planned 1, 2
• Use with caution in patients with bilateral renal artery stenosis (risk of acute renal failure) 1
• Losartan is not removed by hemodialysis 6

Combination Therapy

Add hydrochlorothiazide 12.5 mg daily if blood pressure target (<130/80 mmHg) is not achieved with losartan 50 mg daily, then increase losartan to 100 mg daily before increasing hydrochlorothiazide to 25 mg daily. 2

• The combination of losartan 50 mg plus hydrochlorothiazide 12.5 mg produces blood pressure reductions of 15.5/9.2 mmHg. 2
• Losartan has no clinically significant drug interactions with hydrochlorothiazide, warfarin, or digoxin. 6
• If additional blood pressure control is needed, add a dihydropyridine calcium channel blocker or increase diuretic dose rather than exceeding losartan 100 mg daily. 1

Special Populations

Pediatric Patients (6-16 years):

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

Hepatic Impairment:

• Start with 25 mg once daily in mild-to-moderate hepatic impairment 2
• Not studied in severe hepatic impairment 2

Renal Impairment:

• No dose adjustment needed for any degree of renal insufficiency 6
• Continue therapy even in advanced CKD unless specific contraindications develop 7

Pharmacokinetic Considerations

• Losartan reaches peak concentration 1-2 hours after administration 6
• Approximately 14% is converted to E-3174, an active metabolite 10-40 times more potent than losartan with a half-life of 6-9 hours 6
• Can be administered without regard to food 6
• Linear, dose-proportional pharmacokinetics with no accumulation on repeated dosing 6