What is the recommended dosing for Losartan (Angiotensin II receptor antagonist) in a patient with hypertension or diabetic nephropathy, considering potential impaired renal function or history of heart failure?

Losartan Dosing Recommendations

For hypertension, start losartan at 50 mg once daily and titrate to 100 mg once daily as needed for blood pressure control; for diabetic nephropathy, titrate to the target dose of 100 mg once daily; and for heart failure with reduced ejection fraction, the target dose is 150 mg once daily, though this exceeds the FDA-approved maximum for hypertension. 1, 2, 3

Standard Dosing by Indication

Hypertension

• Start with 50 mg once daily and increase to a maximum of 100 mg once daily based on blood pressure response 1
• For patients with possible intravascular depletion (e.g., on diuretic therapy), start with 25 mg once daily 1
• Target blood pressure should be <130/80 mmHg in most adults with hypertension 2
• If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5-25 mg daily rather than exceeding the maximum losartan dose 2, 1

Diabetic Nephropathy

• Start with 50 mg once daily and titrate to the target dose of 100 mg once daily based on blood pressure response 1
• The 100 mg daily dose is significantly more effective than 50 mg daily in reducing albuminuria and blood pressure in diabetic nephropathy 3
• Losartan 100 mg daily reduced albuminuria by 48% compared to 30% with 50 mg daily (P<0.01) 3
• Continue losartan even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 2

Heart Failure with Reduced Ejection Fraction

• Target dose is 150 mg once daily for optimal cardiovascular outcomes, though this exceeds the FDA-approved maximum for hypertension 2, 4
• The HEAAL trial demonstrated that 150 mg daily was superior to 50 mg daily, with a 10% relative risk reduction in death or heart failure hospitalization 2
• Start with 50 mg once daily and titrate gradually every 2 weeks to target or maximally tolerated dose 2
• At minimum, achieve 50% of target dose (75 mg daily) for meaningful benefit 2

Dosing Frequency Options

Losartan can be administered once or twice daily, but the total daily dose should not exceed 100 mg for hypertension 2

• Once-daily dosing of the full dose is more commonly recommended and simplifies adherence 2
• Twice-daily dosing (e.g., 50 mg BID for a total of 100 mg daily) is acceptable if more consistent 24-hour coverage is desired 2

Special Population Adjustments

Hepatic Impairment

• Start with 25 mg once daily in patients with mild-to-moderate hepatic impairment due to 5-fold increase in plasma concentrations 1, 2
• Losartan has not been studied in severe hepatic impairment and should be avoided 1

Renal Impairment

• No dose adjustment is necessary for various degrees of renal insufficiency 5
• Losartan is recommended for chronic kidney disease with eGFR >30 mL/min per 1.73 m² 2
• Regular monitoring of electrolyte balance and serum creatinine is essential 2

Elderly or Frail Patients

• Initial doses and titration should be more gradual 2
• Monitor blood pressure in both sitting and standing positions due to increased risk of postural hypotension 2

Critical Monitoring Requirements

Initial and Dose-Change Monitoring

• Check serum creatinine/eGFR and potassium within 1-2 weeks after initiating therapy or increasing doses 2, 6
• Monitor blood pressure response to guide titration 1

Maintenance Monitoring

• Check serum creatinine/eGFR and potassium at least annually during stable therapy 2
• Monitor potassium every 3-6 months in patients at higher risk for hyperkalemia 2

Acceptable Changes During Therapy

• An increase in creatinine up to 50% above baseline or to 3 mg/dL is acceptable 7
• If creatinine rises by 100% or exceeds 4 mg/dL, seek specialist advice 7
• Asymptomatic hypotension does not require treatment changes 7

Absolute Contraindications and Critical Safety Warnings

Never Combine with Other RAS Inhibitors

• Do not combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren) due to increased risk of hyperkalemia, syncope, and acute kidney injury without additional benefit 2, 4, 6
• The triple combination of ARB + ACE inhibitor + mineralocorticoid receptor antagonist is particularly dangerous 7

Pregnancy

• Discontinue losartan immediately in women considering pregnancy or who become pregnant due to serious fetal toxicity risk 2

Hyperkalemia Management

• Avoid potassium supplements, potassium-sparing diuretics, and "low-salt" substitutes with high potassium content 7
• If potassium >5.0 mmol/L, seek specialist advice and implement potassium-lowering strategies before discontinuing losartan 2
• Do not prematurely discontinue losartan for hyperkalemia; instead, manage potassium levels with dietary modification, diuretic adjustment, or potassium binders 2

Volume Depletion

• Counsel patients to temporarily hold losartan during acute illness with vomiting or diarrhea to prevent hypotension and acute kidney injury 4

Common Pitfalls to Avoid

Underdosing

• Less than 25% of patients are ever titrated to target doses in clinical practice 2
• Many physicians use doses that are too low to provide optimal benefits, particularly in heart failure 7
• Higher doses provide greater benefits than lower doses, with little evidence that medium-range doses approximate the benefits of target doses 2

Premature Discontinuation

• Do not stop losartan for mild hyperkalemia without first attempting potassium-lowering strategies 2
• Temporary dose reductions may be necessary, but efforts should be made to return to target doses when possible 7

NSAID Interactions

• Avoid NSAIDs unless essential, as they may attenuate diuretic effects and cause renal impairment 7

Practical Titration Algorithm

1. Start: 50 mg once daily (25 mg if hepatic impairment or volume depletion) 1, 2
2. Monitor: Check blood pressure, creatinine/eGFR, and potassium within 1-2 weeks 2
3. Titrate: If tolerated and blood pressure not at goal, increase to 100 mg once daily after 2 weeks 1, 2
4. Reassess: Check blood pressure, creatinine/eGFR, and potassium 1-2 weeks after dose increase 2
5. Optimize: If blood pressure remains uncontrolled on 100 mg daily, add hydrochlorothiazide 12.5-25 mg daily 2, 1
6. For heart failure: Continue titration to 150 mg daily if tolerated, monitoring closely 2