What are the recommended adult dosages of losartan for hypertension, heart failure, and diabetic nephropathy, including adjustments for elderly patients, hepatic impairment, and renal impairment?

Losartan Dosing Recommendations

For hypertension, start losartan at 50 mg once daily and titrate to 100 mg once daily after 2–4 weeks if blood pressure remains ≥140/90 mmHg; for heart failure with reduced ejection fraction, target 100–150 mg daily; and for diabetic nephropathy, aim for 100 mg once daily. 1

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Standard Dosing by Indication

Hypertension

• Initial dose: 50 mg once daily 1
• Target dose: 100 mg once daily 1, 2
• Maximum dose: 100 mg daily for hypertension (do not exceed) 1, 2
• Re-evaluate blood pressure every 2–4 weeks during titration, aiming to reach target <130/80 mmHg within 3 months 1

Heart Failure with Reduced Ejection Fraction

• Starting dose: 50 mg once daily 1
• Target dose: 100–150 mg once daily 1
• The HEAAL trial demonstrated that 150 mg daily was superior to 50 mg daily, achieving a 10% relative risk reduction in death or heart failure hospitalization (P=0.027) 1
• Titrate no more frequently than every 2 weeks to target or maximally tolerated doses 1

Diabetic Nephropathy

• Target dose: 100 mg once daily 1, 3
• A study in type 1 diabetic patients with nephropathy showed losartan 100 mg daily reduced albuminuria by 48% and was significantly more effective than 50 mg daily (P<0.01) 3
• The RENAAL trial demonstrated that losartan 100 mg reduced the risk of doubling serum creatinine by 28% (P=0.002) in patients with diabetic nephropathy and macroalbuminuria 1

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Dosing Frequency Options

• Once-daily dosing: Preferred for adherence; administer 50–100 mg as a single morning or evening dose 1, 2
• Twice-daily dosing: Acceptable alternative; the total daily dose of 100 mg can be split into 50 mg twice daily for more consistent 24-hour coverage 1
• Both once-daily and twice-daily regimens are guideline-supported by the American College of Cardiology/American Heart Association 1

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Special Populations

Elderly Patients (≥75 years)

• Start at low doses to avoid precipitating hypotension or renal insufficiency 4
• Increase doses more gradually (every 2–4 weeks rather than weekly) 1
• Measure blood pressure in both sitting and standing positions at 1 minute and 3 minutes after standing to detect orthostatic hypotension 1
• Monitor for dizziness, falls, and fatigue, which are more common in this age group 4

Hepatic Impairment

• Starting dose: 25 mg once daily due to a 5-fold increase in losartan plasma concentrations in patients with hepatic dysfunction 1
• Titrate cautiously with close monitoring 1

Renal Impairment

• No dose adjustment required for mild to moderate renal impairment 2, 5
• Losartan is recommended for chronic kidney disease with eGFR >30 mL/min per 1.73 m² 1
• For eGFR <30 mL/min, use with caution and monitor renal function and potassium closely 1
• Losartan is not removed by hemodialysis 2

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Combination Therapy

Adding a Diuretic

• If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5–25 mg once daily 1
• Fixed-dose combination products improve adherence 1
• The combination provides additive blood pressure-lowering effects 5

Triple Therapy

• For resistant hypertension, add a dihydropyridine calcium-channel blocker (e.g., amlodipine) to create ARB + diuretic + CCB triple therapy 1
• If triple therapy fails, add spironolactone 25 mg daily as the preferred fourth agent 1

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Critical Monitoring Requirements

Renal Function and Electrolytes

• Check serum creatinine/eGFR and potassium within 1–2 weeks after initiating therapy or increasing doses 1
• Monitor at least annually during maintenance therapy 1
• An increase in creatinine up to 0.3 mg/dL is expected and reflects hemodynamic changes rather than tubular injury 1

Blood Pressure

• Reassess office blood pressure every 2–4 weeks during titration 1
• Home blood pressure ≥135/85 mmHg corresponds to office hypertension ≥140/90 mmHg 1

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Absolute Contraindications and Safety Warnings

Pregnancy

• Losartan is absolutely contraindicated throughout pregnancy due to serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death) 1
• Discontinue immediately upon pregnancy detection and switch to pregnancy-compatible agents (methyldopa, labetalol, or extended-release nifedipine) 1

Dual RAAS Blockade

• Never combine losartan with ACE inhibitors or direct renin inhibitors (e.g., aliskiren) 1
• This combination increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit 1
• The VALIANT trial demonstrated higher discontinuation rates and no mortality benefit with dual therapy 1

Drug Interactions

• Avoid NSAIDs unless essential, as they attenuate diuretic effects and may cause renal impairment 1
• Avoid potassium supplements, potassium-sparing diuretics, and "low-salt" substitutes with high potassium content 1

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Common Pitfalls to Avoid

Underdosing

• Less than 25% of patients are ever titrated to target doses in clinical practice 1
• Higher doses provide greater benefits than lower doses, with little evidence that medium-range doses approximate the benefits of target doses 1
• For heart failure, the 50 mg daily dose appears inferior to ACE inhibitors for mortality reduction 1

Premature Discontinuation for Hyperkalemia

• Implement potassium-lowering strategies (dietary restriction, diuretic adjustment, patiromer or sodium zirconium cyclosilicate) before stopping losartan 1
• Mild hyperkalemia (K+ 5.0–5.5 mmol/L) can often be managed without discontinuation 1

Relying on Monotherapy Alone

• Combination therapy with agents from different classes yields better blood pressure control than dose escalation alone 1
• For grade 2 hypertension (≥160/100 mmHg), initiate two antihypertensive agents from the outset 1

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Practical Dosing Algorithm

1. Start: Losartan 50 mg once daily (25 mg if hepatic impairment) 1
2. Reassess: Blood pressure, creatinine, and potassium at 1–2 weeks 1
3. Titrate: If BP ≥140/90 mmHg and well-tolerated, increase to 100 mg once daily after 2–4 weeks 1
4. Add therapy: If BP remains uncontrolled on 100 mg, add hydrochlorothiazide 12.5–25 mg daily 1
5. Intensify: If still uncontrolled, add a calcium-channel blocker for triple therapy 1
6. Monitor: Recheck creatinine and potassium 1–2 weeks after each dose change, then every 3–6 months 1