What is the recommended initial dose of losartan for an adult with hypertension, and how should it be adjusted for elderly patients, moderate renal impairment, volume depletion, heart failure, or diabetic nephropathy?

Starting Dose of Losartan

For adults with uncomplicated hypertension, initiate losartan at 50 mg once daily, then titrate to 100 mg once daily after 2–4 weeks if blood pressure remains ≥140/90 mmHg. 1

Standard Adult Dosing for Hypertension

• Begin with 50 mg once daily as the usual starting dose for most adults with hypertension. 1
• Titrate to 100 mg once daily as needed to achieve blood pressure control, which is the maximum recommended dose for hypertension. 1
• The 50–100 mg daily dose range produces statistically significant blood pressure reductions of 5.5–10.5/3.5–7.5 mmHg compared to placebo, with the 150 mg dose providing no additional benefit over 50–100 mg. 1
• Target blood pressure is <130/80 mmHg for most adults to reduce cardiovascular risk. 2

Dose Adjustments for Special Populations

Volume Depletion or Diuretic Therapy

• Start with 25 mg once daily in patients with possible intravascular volume depletion (e.g., those on diuretic therapy) to minimize the risk of hypotension. 1
• This lower starting dose reduces the risk of first-dose hypotension, though this complication is uncommon with losartan. 3, 4

Elderly Patients (≥65 Years)

• No dose adjustment is required for elderly patients; the standard 50 mg starting dose is appropriate. 3
• Losartan 50–100 mg once daily produces blood pressure reductions ≤26/20 mmHg in elderly patients, with efficacy similar to captopril, atenolol, enalapril, and felodipine. 3
• In frail or very elderly patients (≥85 years), consider more gradual titration every 2–4 weeks rather than weekly, and monitor for orthostatic hypotension by checking blood pressure in both sitting and standing positions. 5

Moderate Renal Impairment

• No dose adjustment is necessary for patients with mild to moderate renal impairment (eGFR 30–60 mL/min/1.73 m²). 3, 6
• Losartan 50–100 mg once daily effectively reduces blood pressure in patients with chronic renal insufficiency (creatinine clearance 10–60 mL/min/1.73 m²) without adversely affecting glomerular filtration rate or effective renal plasma flow. 6
• Monitor serum creatinine and potassium within 1–2 weeks after initiating therapy or increasing doses, then at least annually during maintenance. 5
• An increase in creatinine up to 50% above baseline or to 3 mg/dL is acceptable; if creatinine rises by 100% or exceeds 4 mg/dL, seek specialist consultation. 7

Hepatic Impairment

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

Heart Failure

• Begin with 50 mg once daily and titrate to a target dose of 100–150 mg once daily for heart failure with reduced ejection fraction. 5
• 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). 5
• Titrate no more frequently than every 2 weeks to target or maximally tolerated doses. 5
• In patients with baseline low blood pressure, start at the lowest dose and up-titrate slowly with small increments every 1–2 weeks, monitoring closely for symptomatic hypotension. 5

Diabetic Nephropathy

• Start with 50 mg once daily and increase to 100 mg once daily based on blood pressure response. 1
• The target dose of 100 mg once daily for diabetic nephropathy is supported by the RENAAL trial, which demonstrated a 20% reduction in the primary composite renal outcome (P=0.01) and a 28% reduction in doubling of serum creatinine (P=0.002). 5
• Check serum creatinine/eGFR and potassium within 1–2 weeks after starting or changing the dose, then monitor at least annually. 5

Combination Therapy Considerations

• Add hydrochlorothiazide 12.5–25 mg daily if blood pressure remains uncontrolled on losartan 100 mg daily after 4–8 weeks, as this combination provides additive blood pressure-lowering effects of approximately 15.5/9.2 mmHg. 1, 5
• For patients presenting with grade 2 hypertension (≥160/100 mmHg), initiate two antihypertensive agents from the outset (e.g., losartan plus a thiazide diuretic or calcium-channel blocker). 5
• Never combine losartan with ACE inhibitors or direct renin inhibitors (e.g., aliskiren), as dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit. 2, 5, 7

Monitoring and Follow-Up

• Reassess blood pressure every 2–4 weeks after initiating therapy or adjusting doses, with the goal of reaching target blood pressure within 3 months. 2, 5
• Home blood pressure monitoring is recommended; a home reading ≥135/85 mmHg corresponds to office hypertension ≥140/90 mmHg. 5
• Monitor serum potassium and creatinine within 1–2 weeks of starting losartan or increasing doses, especially in patients with diabetes, chronic kidney disease, or those on concomitant potassium-sparing agents. 5

Critical Safety Considerations

• Losartan is absolutely contraindicated in pregnancy due to serious fetal toxicity (renal dysfunction, oligohydramnios, skull hypoplasia, fetal death); discontinue immediately upon pregnancy detection and switch to pregnancy-compatible antihypertensives such as methyldopa, labetalol, or extended-release nifedipine. 5
• Asymptomatic hypotension does not require treatment changes, but if symptomatic hypotension occurs, reconsider the need for nitrates, calcium-channel blockers, and other vasodilators and reduce or stop them if possible. 7
• Avoid NSAIDs unless essential, as they may attenuate diuretic effects and cause renal impairment. 7

Common Pitfalls to Avoid

• Underdosing is widespread in clinical practice, with less than 25% of patients ever titrated to target doses; ensure adequate titration to 100 mg daily for hypertension and 100–150 mg daily for heart failure to achieve optimal cardiovascular outcomes. 5, 8
• Do not prematurely discontinue losartan for mild hyperkalemia (K⁺ 5.0–5.5 mmol/L); implement potassium-lowering strategies (discontinue potassium supplements, avoid "low-salt" substitutes with high potassium content, adjust diuretics) before stopping the medication. 5
• The 50 mg dose is likely suboptimal for many patients; clinical studies support that higher doses (100 mg daily) provide better cardiovascular outcomes. 8, 5