What are the dosing recommendations, contraindications, precautions, monitoring requirements, drug interactions, and special considerations for losartan in adults (including those with renal or hepatic impairment, pregnancy, elderly, diabetes, chronic kidney disease) and in pediatric patients?

Losartan: Comprehensive Clinical Guide

Dosing Recommendations

For hypertension, initiate losartan at 50 mg once daily and titrate to 100 mg once daily if blood pressure remains ≥140/90 mmHg after 2–4 weeks; for heart failure with reduced ejection fraction, the target dose is 100–150 mg daily based on outcomes data. 1, 2

Standard Dosing by Indication

Hypertension:

• Start 50 mg once daily 1, 3
• Maximum dose: 100 mg daily (can be given as 50 mg twice daily or 100 mg once daily) 1, 2, 4
• Re-evaluate blood pressure every 2–4 weeks during titration 2
• Target blood pressure: <130/80 mmHg for most adults 2

Heart Failure with Reduced Ejection Fraction:

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

Diabetic Nephropathy:

• Target dose: 100 mg once daily 2
• The RENAAL trial showed losartan 100 mg reduced the primary composite renal outcome by 20% (P=0.01) and lowered the risk of doubling serum creatinine by 28% (P=0.002) 2

Pediatric Dosing (Ages 6–16 Years)

• Weight <50 kg: 2.5–50 mg once daily 3
• Weight ≥50 kg: 5–100 mg once daily 3
• The lowest doses (2.5 mg in <50 kg; 5 mg in ≥50 kg) did not offer consistent antihypertensive efficacy 3
• Safety and effectiveness not established in children under age 6 or with GFR <30 mL/min/1.73 m² 3

Contraindications

Losartan is absolutely contraindicated in pregnancy due to serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death; discontinue immediately upon pregnancy detection. 1, 2, 3

Absolute Contraindications

• Pregnancy (all trimesters): Causes serious fetal toxicity 1, 2, 3
• Combination with ACE inhibitors or direct renin inhibitors (aliskiren): Increases risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit 1, 2
• History of angioedema with ARBs: Do not use if patient has prior ARB-induced angioedema 1

Relative Contraindications

• Severe bilateral renal artery stenosis: Risk of acute renal failure 1
• Severe hepatic impairment: Losartan has not been studied in this population 3

Special Populations

Hepatic Impairment

Start losartan at 25 mg once daily in patients with mild-to-moderate hepatic impairment, as plasma concentrations are 5-fold higher than in healthy volunteers. 1, 3

• Losartan plasma concentrations increase 5-fold in hepatic impairment 3
• Active metabolite (E-3174) concentrations increase 1.7-fold 3
• Not studied in severe hepatic impairment 3

Renal Impairment

• No dose adjustment necessary in patients with renal impairment unless volume depleted 3
• Can be continued as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit 2
• Losartan is not removed by hemodialysis 4
• Monitor serum creatinine/eGFR and potassium within 1–2 weeks after initiation or dose changes 2

Elderly Patients (≥65 Years)

• No initial dose adjustment required in elderly patients 3, 5, 6
• For patients ≥75 years or frail elderly, initiate at a low dose and titrate more gradually (every 2–4 weeks) 2
• Measure blood pressure in both sitting and standing positions (at 1 and 3 minutes after standing) to detect orthostatic hypotension 2
• Monitor closely for dizziness, falls, and fatigue 2
• Continue lifelong antihypertensive treatment beyond age 85 when well tolerated 2

Pregnancy and Lactation

• Discontinue immediately upon pregnancy detection and switch to pregnancy-compatible agents (methyldopa, labetalol, or extended-release nifedipine) 2
• Women of childbearing potential should be counseled about fetal risks 2

Race Considerations

• Black patients may have a lower response to losartan monotherapy due to lower renin activity 3, 5
• The LIFE study showed Black patients with hypertension and left ventricular hypertrophy had better outcomes with atenolol than losartan 3
• Consider adding hydrochlorothiazide for improved efficacy in Black patients 2

Monitoring Requirements

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

Initial Monitoring (Within 1–2 Weeks)

• Serum creatinine and eGFR 2
• Serum potassium 2
• Blood pressure (office and home measurements) 2
• Orthostatic blood pressure in elderly patients 2

Ongoing Monitoring

• Blood pressure every 2–4 weeks until target achieved 2
• Annual monitoring of renal function and potassium during maintenance 2
• More frequent monitoring in patients with chronic kidney disease, diabetes, or on potassium-sparing agents 1, 2

Expected Laboratory Changes

• A modest, transient increase in serum creatinine of 0.1–0.3 mg/dL is common and reflects hemodynamic changes rather than tubular injury 2
• Discontinuation is not required unless urinalysis shows acute tubular necrosis 2

Drug Interactions

Contraindicated Combinations

Never combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren), as dual RAAS blockade increases hyperkalemia, syncope, and acute kidney injury without improving outcomes. 1, 2

• ACE inhibitors: Contraindicated combination 1, 2
• Direct renin inhibitors (aliskiren): Contraindicated combination 1, 2

Significant Interactions

• Potassium supplements or potassium-sparing diuretics: Increased risk of hyperkalemia, especially in chronic kidney disease 1, 2
• NSAIDs: May reduce antihypertensive effect and worsen renal function 1
• Lithium: Potential for lithium toxicity (monitor lithium levels) 1

Favorable Interaction Profile

• No clinically relevant interactions with hydrochlorothiazide, warfarin, or digoxin 4
• Losartan has a favorable drug-drug interaction profile overall 4
• Can be taken without regard to food 3, 4

Combination Therapy

If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5–25 mg daily rather than exceeding the maximum losartan dose. 1, 2

Preferred Combinations

• Losartan + hydrochlorothiazide: Provides additive blood pressure-lowering effects 1, 2
  • Addition of HCTZ 12.5 mg to losartan 50 mg resulted in placebo-adjusted reductions of 15.5/9.2 mmHg 3
• Losartan + dihydropyridine calcium channel blocker (e.g., amlodipine): For triple therapy if dual therapy insufficient 2

Triple Therapy for Resistant Hypertension

• ARB + thiazide diuretic + dihydropyridine CCB 2
• If still uncontrolled, add spironolactone 25 mg daily as fourth agent 2

Safety Considerations and Adverse Effects

Losartan has a favorable tolerability profile with adverse event rates similar to placebo; the most common side effects are headache, dizziness, and upper respiratory infection. 7, 6

Common Adverse Effects

• Headache 7
• Upper respiratory tract infection 7
• Dizziness (occurs more frequently than placebo by ≥1%) 7
• Asthenia/fatigue 7
• Cough: Occurs in only 3.1% (vs. 2.6% with placebo), much lower than ACE inhibitors 7

Serious Adverse Effects (Rare)

• Hyperkalemia: Especially in chronic kidney disease, diabetes, or with potassium-sparing agents 1, 2
• Acute renal failure: In severe bilateral renal artery stenosis 1
• Angioedema: Lower incidence than ACE inhibitors but still possible 1, 2
• Hypotension: Particularly in volume-depleted patients 2

Angioedema Considerations

• Patients with prior ACE inhibitor-induced angioedema can receive an ARB beginning 6 weeks after ACE inhibitor discontinuation 1
• Extreme caution required in this population 2

Common Pitfalls and How to Avoid Them

Underdosing

Less than 25% of patients are ever titrated to target doses in clinical practice, resulting in suboptimal outcomes. 2

• Solution: Actively titrate to 100 mg daily for hypertension and 100–150 mg daily for heart failure 2
• Higher doses provide greater benefits than lower doses 2
• The 50 mg dose appears inferior to ACE inhibitors for mortality reduction in heart failure 2

Premature Discontinuation for Hyperkalemia

• Solution: Implement potassium-lowering strategies (dietary restriction, diuretics, potassium binders) before stopping losartan 2
• The cardiovascular and renal benefits often outweigh mild hyperkalemia 2

Combining with ACE Inhibitors

• Solution: Never combine losartan with ACE inhibitors; this is contraindicated and increases adverse events without benefit 1, 2
• The VALIANT trial demonstrated increased risks with dual RAAS blockade 2

Inadequate Monitoring

• Solution: Always check potassium and creatinine within 1–2 weeks of initiation or dose changes 2
• Do not assume stability without laboratory confirmation 2

Switching Timing After ACE Inhibitor Angioedema

• Solution: Wait at least 6 weeks after ACE inhibitor discontinuation before starting losartan in patients with prior angioedema 1

Pharmacokinetics

• Absorption: Rapid, with peak concentrations at 1–2 hours 4
• Active metabolite (E-3174): 10–40-fold more potent than losartan; half-life 6–9 hours 4
• Metabolism: Via CYP3A4, 2C9, and 2C10; approximately 14% converted to E-3174 4
• Linearity: Dose-proportional pharmacokinetics 4
• No accumulation with repetitive administration 4

Clinical Efficacy

• Blood pressure reduction: 5.5–10.5/3.5–7.5 mmHg compared to placebo at doses of 50–150 mg daily 3
• Trough-to-peak ratio: 50–95% for systolic and 60–90% for diastolic responses 3
• 24-hour control: Provides gradual blood pressure reduction without affecting circadian rhythm 5
• Comparable efficacy to atenolol, felodipine, and enalapril 5, 6

1, 2, 3, 4, 5, 8, 7, 6