What is the maximum recommended daily dose of losartan in adults, and how should it be adjusted for patients with severe renal impairment, the elderly, or those who are volume‑depleted?

Maximum Dosing of Losartan

The maximum recommended daily dose of losartan is 100 mg once daily for hypertension, though 150 mg daily may be used for heart failure with reduced ejection fraction based on outcomes data from the HEAAL trial. 1, 2

Standard Maximum Dosing by Indication

Hypertension

• The FDA-approved maximum dose is 100 mg once daily, which can be administered as a single dose or split into 50 mg twice daily 1, 3
• The American College of Cardiology/American Heart Association guidelines confirm this 100 mg daily ceiling for hypertension management 2
• If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5–25 mg rather than exceeding the maximum losartan dose 2

Heart Failure with Reduced Ejection Fraction

• The target dose is 100–150 mg once daily based on the HEAAL trial, which demonstrated that 150 mg was superior to 50 mg with a 10% relative risk reduction in death or heart failure hospitalization (P=0.027) 2
• The European Society of Cardiology recommends 150 mg as the target dose for heart failure 2

Diabetic Nephropathy

• The usual starting dose is 50 mg once daily, increased to 100 mg once daily based on blood pressure response 1
• The KDOQI guidelines list the dosing range as 25–100 mg daily, not exceeding 100 mg 2
• Clinical evidence supports 100 mg daily as the optimal dose for renoprotection in type 1 diabetic nephropathy 4

Dose Adjustments for Special Populations

Volume Depletion

• Start with 25 mg once daily in patients with possible intravascular depletion (e.g., those on diuretic therapy) to reduce the risk of hypotension 1
• After confirming tolerability, titrate to standard dosing targets 1

Severe Renal Impairment

• No dose adjustment is necessary in patients with renal impairment unless the patient is also volume depleted 1
• Losartan is not removed by hemodialysis 3
• Monitor serum creatinine and potassium within 1–2 weeks after initiation or dose changes, especially in patients with chronic kidney disease 2

Elderly Patients (≥65 Years)

• No routine dose adjustment is required based on age alone; clinical trials showed no overall differences in effectiveness or safety between elderly and younger patients 1
• For patients ≥75 years or frail elderly, consider initiating at a lower dose (25–50 mg) and titrating more gradually (every 2–4 weeks) to monitor for symptomatic hypotension and orthostatic changes 2
• Measure blood pressure in both sitting and standing positions at 1 and 3 minutes after standing to detect orthostatic hypotension 2

Hepatic Impairment

• Start with 25 mg once daily in patients with mild-to-moderate hepatic impairment, as plasma concentrations are approximately 5-fold higher than in healthy individuals 1
• Losartan has not been studied in severe hepatic impairment and should be avoided 1

Critical Safety Considerations

Absolute Contraindications to Higher Doses

• Never combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren), as dual RAAS blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without cardiovascular benefit 2
• Pregnancy: Losartan is absolutely contraindicated in all trimesters due to serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death) 2

Monitoring Requirements

• Check serum creatinine/eGFR and potassium within 1–2 weeks after initiating therapy or increasing doses 2
• Monitor at least annually during maintenance therapy 2
• More frequent monitoring is required in patients with chronic kidney disease, diabetes, or those receiving potassium-sparing agents 2

Common Pitfalls to Avoid

• Underdosing is widespread: Less than 25% of patients are ever titrated to target doses in clinical practice, yet higher doses provide greater benefits than lower doses 2
• Do not exceed 100 mg daily for hypertension alone; instead add a second agent from a different class (thiazide diuretic or calcium-channel blocker) 2, 1
• For heart failure, do not settle for 50 mg daily, as this dose appears inferior to ACE inhibitors for mortality reduction; aim for 100–150 mg daily 2
• Avoid premature discontinuation for mild creatinine elevations (0.1–0.3 mg/dL increase); this reflects expected hemodynamic changes rather than tubular injury 2