What is the recommended starting dose and titration schedule for Losartan in an adult with hypertension, including monitoring of serum potassium, renal function, and adverse effects?

Losartan Dosing: Starting at 25mg and Titrating to 50mg Daily

Start losartan 25mg once daily and increase to 50mg once daily after 2–4 weeks if blood pressure remains ≥140/90 mmHg or heart failure symptoms persist, with the ultimate target dose being 100mg daily for hypertension and 100–150mg daily for heart failure with reduced ejection fraction. 1

Initial Dosing Strategy

• Begin with losartan 25mg once daily in elderly patients (≥75 years), those with hepatic impairment, or volume-depleted individuals to minimize hypotension risk 1, 2
• For hepatic impairment specifically, plasma losartan concentrations are approximately five-fold higher than in healthy individuals, making the 25mg starting dose essential 1
• Standard starting dose is 50mg once daily for most adults with hypertension or heart failure, but 25mg is appropriate for high-risk populations 1, 2

Titration Schedule and Target Doses

• Increase from 25mg to 50mg after 2–4 weeks if blood pressure remains elevated (≥140/90 mmHg) or symptoms persist 1
• Further titrate from 50mg to 100mg once daily after an additional 2–4 weeks if needed for blood pressure control 1
• Maximum recommended dose for hypertension is 100mg once daily, which can be given as a single dose or split into 50mg twice daily 1, 2
• For heart failure with reduced ejection fraction, target 100–150mg daily; the HEAAL trial demonstrated that 150mg daily was superior to 50mg daily with a 10% relative risk reduction in death or heart failure hospitalization 1

Critical Monitoring Requirements

• Check serum creatinine/eGFR and potassium within 1–2 weeks after starting losartan or after any dose increase 1, 3
• Acceptable laboratory changes: A rise in serum creatinine up to 50% and potassium up to 5.5 mEq/L is expected and does not require discontinuation 1
• Hold losartan immediately if potassium ≥6.0 mEq/L or serum creatinine increases to >220 μmol/L (2.5 mg/dL) 3
• Halve the dose if potassium is 5.5–6.0 mEq/L and monitor blood chemistry closely 3
• Recheck blood pressure every 2–4 weeks during titration, aiming for a target of <130/80 mmHg within 3 months 1

Pharmacokinetic Considerations

• Losartan reaches maximum concentrations 1–2 hours post-administration 2
• The active metabolite E3174 is 10- to 40-fold more potent than losartan and has a terminal half-life of 6–9 hours, providing 24-hour blood pressure control 2
• Approximately 14% of losartan is converted to E3174, which contributes substantially to the antihypertensive effect 2
• Losartan can be administered without regard to food 2

When to Add Combination Therapy

• If blood pressure remains ≥140/90 mmHg on losartan 100mg after 4–8 weeks, add hydrochlorothiazide 12.5–25mg once daily 1
• Prefer single-pill fixed-dose combinations (losartan + HCTZ) to improve adherence 1
• For grade 2 hypertension (≥160/100 mmHg), consider starting with two agents (losartan + thiazide or calcium-channel blocker) from the outset 1

Absolute Contraindications

• Pregnancy (all trimesters) – causes serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death 1
• Concurrent use with ACE inhibitors or direct renin inhibitors (aliskiren) – increases risk of hyperkalemia, syncope, and acute kidney injury 2–3-fold without cardiovascular benefit 1, 3
• History of angioedema with ARBs 1
• Severe bilateral renal-artery stenosis – risk of acute renal failure 1
• Baseline potassium >5.0 mEq/L or eGFR <30 mL/min/1.73 m² without specialist consultation 3

Special Population Adjustments

• Elderly (≥75 years): Start at 25mg and titrate more gradually (every 2–4 weeks rather than weekly); monitor closely for dizziness, falls, and orthostatic hypotension 1
• Chronic kidney disease (eGFR 30–60 mL/min): Start at 25–50mg and monitor potassium/creatinine more frequently (every 1–2 weeks initially) 1, 4
• Hemodialysis patients: Losartan is effective and well-tolerated; start at 50mg and titrate to 100mg as needed 4
• Mild-to-moderate hepatic impairment: Start at 25mg once daily due to five-fold increase in plasma concentrations 1

Common Pitfalls to Avoid

• Do not combine losartan with ACE inhibitors – the VALIANT trial showed increased adverse outcomes without benefit 1
• Do not stop losartan for mild creatinine elevations (0.1–0.3 mg/dL) – these reflect expected hemodynamic changes, not tubular injury 1
• Do not underdose – less than 25% of patients are titrated to target doses in clinical practice, yet higher doses provide greater cardiovascular benefits 1
• Do not add potassium supplements routinely – losartan reduces renal potassium excretion, and supplementation may cause dangerous hyperkalemia 5, 1
• Do not use NSAIDs concurrently – they blunt losartan's antihypertensive effect and worsen renal function 1

Drug Interactions Requiring Dose Adjustment

• Potassium-sparing diuretics or potassium supplements: Markedly increase hyperkalemia risk, especially in chronic kidney disease; avoid or monitor potassium every 5–7 days initially 5, 1
• Lithium: Co-administration can precipitate lithium toxicity; monitor lithium levels 1
• NSAIDs: May reduce antihypertensive efficacy and impair renal function 1

Evidence for Dosing Frequency

• Once-daily dosing is standard and preferred for adherence 1, 2
• Twice-daily dosing (e.g., 50mg BID for total 100mg/day) is acceptable per ACC/AHA guidelines, though less commonly recommended 1
• No evidence supports three-times-daily dosing – pivotal trials (OPTIMAAL, VALIANT, HEAAL) used only once- or twice-daily regimens 1

Renal Protection in Advanced Disease

• Losartan retards progression even when initiated late in chronic kidney disease (baseline creatinine 2.0–5.5 mg/dL) 6
• The rate of renal function loss (1/sCr slope) significantly improved after losartan treatment (-0.004 ± 0.002 dl/mg/week before vs. -0.001 ± 0.002 dl/mg/week after, p<0.05) 6
• Continue losartan as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit, with close monitoring 1