What is the recommended initial dose and titration schedule of losartan for an adult with hypertension or proteinuric chronic kidney disease, including adjustments for elderly or frail patients and those with moderate (estimated glomerular filtration rate 30‑60 mL/min/1.73 m²) or severe (estimated glomerular filtration rate <30 mL/min/1.73 m²) renal impairment or on dialysis?

Losartan Dosing for Hypertension and Chronic Kidney Disease

Initial Dosing

Start losartan at 50 mg once daily for adults with hypertension or proteinuric chronic kidney disease, then titrate to 100 mg once daily after 2–4 weeks if blood pressure remains ≥140/90 mmHg or proteinuria persists. 1, 2

• The 50 mg starting dose is appropriate for most adults, including those with mild-to-moderate renal impairment (eGFR 30–60 mL/min/1.73 m²). 3
• No dosage adjustment is required for elderly patients or those with renal dysfunction, as pharmacokinetics remain stable across these populations. 4, 3
• The maximum recommended dose for hypertension is 100 mg once daily, which can be administered as a single dose or split into 50 mg twice daily. 1, 4

Target Dosing for Optimal Outcomes

For heart failure with reduced ejection fraction, the target dose is 100–150 mg daily; 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. 1

• For diabetic nephropathy and proteinuric CKD, the target dose is 100 mg once daily to achieve maximal renoprotective benefit. 2, 5
• Underdosing (≤50 mg daily) fails to deliver the proven cardiovascular and renoprotective effects demonstrated in clinical trials. 1, 6
• Titrate doses no more frequently than every 2 weeks to reach target or maximally tolerated doses. 1

Special Populations

Elderly or Frail Patients (≥75 years)

• Initiate at 50 mg once daily and increase the dose more gradually (every 2–4 weeks rather than weekly). 1
• Measure blood pressure in both sitting and standing positions (after 5 minutes seated, then at 1 minute and 3 minutes after standing) to detect orthostatic hypotension. 1
• Monitor closely for dizziness, falls, and symptomatic hypotension during titration. 1

Hepatic Impairment

• Start at 25 mg once daily in patients with mild-to-moderate hepatic impairment, as plasma concentrations are approximately five-fold higher than in healthy individuals. 1

Renal Impairment

No dosage adjustment is required for patients with eGFR 30–60 mL/min/1.73 m² (moderate renal impairment) or eGFR <30 mL/min/1.73 m² (severe renal impairment). 3

• Losartan 50–100 mg once daily is effective and well-tolerated in patients with chronic renal insufficiency, including those on hemodialysis. 3
• Continue losartan even when eGFR falls below 30 mL/min/1.73 m² for cardiovascular and renoprotective benefit, provided there is no symptomatic hypotension or uncontrolled hyperkalemia. 2
• Losartan is not removed during hemodialysis; no supplemental dosing is required. 4

Monitoring Requirements

Check serum creatinine/eGFR and potassium within 1–2 weeks after initiating losartan or increasing the dose, then at least annually during maintenance therapy. 1, 2

• An increase in serum creatinine up to 30% within the first 4 weeks is expected and does not require discontinuation. 2
• Accept serum potassium up to 5.5 mEq/L; manage hyperkalemia with dietary restriction and potassium-binding agents before reducing or stopping losartan. 2
• Reassess blood pressure every 2–4 weeks during titration, aiming for a target of <130/80 mmHg within 3 months. 1

Combination Therapy

If blood pressure remains ≥140/90 mmHg on losartan 100 mg daily after 4–8 weeks, add hydrochlorothiazide 12.5–25 mg once daily. 1

• Fixed-dose combination products (losartan + hydrochlorothiazide) markedly improve adherence and are strongly recommended. 1
• Alternative second-line agents include dihydropyridine calcium channel blockers (e.g., amlodipine 5–10 mg daily). 1
• For resistant hypertension uncontrolled on triple therapy (ARB + thiazide + CCB), add spironolactone 25 mg daily as the fourth agent. 1

Critical Safety Considerations

Do not combine losartan with ACE inhibitors or direct renin inhibitors (e.g., aliskiren); dual RAAS blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit. 7, 1, 2

• Losartan is absolutely contraindicated in all trimesters of pregnancy due to serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death). 1
• Avoid in patients with severe bilateral renal-artery stenosis due to risk of acute renal failure. 1
• Monitor for angioedema, though it is less frequent than with ACE inhibitors. 1

Common Pitfalls to Avoid

• Do not stop losartan for mild creatinine increases (<30%): This reflects expected hemodynamic changes, not renal injury. 2
• Do not underdose: The proven benefits in clinical trials were achieved with 100 mg daily (or 150 mg for heart failure), not lower doses. 1, 6
• Do not discontinue prematurely for hyperkalemia: Implement potassium-lowering strategies before reducing or stopping the medication. 2
• Do not rely on monotherapy dose escalation alone: Combination therapy with agents from different classes yields better blood pressure control. 1

Acute Kidney Injury Management

Temporarily discontinue losartan during acute kidney injury, as it can exacerbate kidney dysfunction through hemodynamic effects on glomerular filtration pressure. 8

• Reintroduce losartan only after GFR has stabilized, volume status is optimized, mean arterial pressure is >65 mmHg, and serum potassium is <5.5 mEq/L. 8
• Monitor serum creatinine, eGFR, and potassium within 1 week of restarting after AKI recovery. 8
• Continuing losartan after AKI recovery is associated with reduced mortality and cardiovascular events without increased recurrent AKI risk. 8