What are the indications, dosing regimen, contraindications, adverse effects, and monitoring recommendations for losartan in an adult patient, including dose adjustments for renal impairment and the elderly?

Losartan: Comprehensive Clinical Guide

Indications

Losartan is FDA-approved for three primary indications: hypertension in adults and children ≥6 years, reduction of cardiovascular events in hypertensive patients with left ventricular hypertrophy, and nephropathy in type 2 diabetic patients. 1

• Hypertension: First-line therapy for essential hypertension in adults and children ≥6 years with eGFR ≥30 mL/min/1.73 m² 1
• Cardiovascular risk reduction: Specifically for hypertensive patients with left ventricular hypertrophy to reduce stroke, myocardial infarction, and cardiovascular death 1
• Diabetic nephropathy: Type 2 diabetes with proteinuria/albuminuria to slow progression of kidney disease 1
• Heart failure with reduced ejection fraction: Alternative to ACE inhibitors when ACE inhibitors are not tolerated 2

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Dosing Regimen

Adult Hypertension

Start losartan at 50 mg once daily and titrate to 100 mg once daily after 2-4 weeks if blood pressure remains ≥140/90 mmHg; this provides near-maximal antihypertensive effect. 2, 1

• Initial dose: 50 mg once daily (can be taken at any time of day, with or without food) 1, 3
• Target dose: 100 mg once daily 2, 1
• Maximum dose: 100 mg once daily for hypertension 1, 3
• Titration schedule: Re-evaluate blood pressure every 2-4 weeks during titration, aiming to reach target BP <130/80 mmHg within 3 months 2

Combination Therapy for Hypertension

If blood pressure remains uncontrolled on losartan 100 mg daily, add hydrochlorothiazide 12.5-25 mg daily as a fixed-dose combination rather than exceeding 100 mg losartan. 2

• For grade 2 hypertension (≥160/100 mmHg), initiate two agents from the outset: losartan plus either hydrochlorothiazide or a dihydropyridine calcium channel blocker 2
• If dual therapy is insufficient, add a third agent (ARB + thiazide diuretic + calcium channel blocker) 2
• Single-pill combination products are strongly preferred to enhance adherence 2

Heart Failure with Reduced Ejection Fraction

The target dose for heart failure is 100-150 mg once daily; the HEAAL trial demonstrated that 150 mg was superior to 50 mg with a 10% relative risk reduction in death or heart failure hospitalization. 2

• Starting dose: 50 mg once daily 2
• Target dose: 100-150 mg once daily 2
• Titration: Adjust no more frequently than every 2 weeks to target or maximally tolerated dose 2
• In patients with low baseline blood pressure, start at the lowest dose and up-titrate slowly with small increments every 1-2 weeks 2

Diabetic Nephropathy

For diabetic nephropathy with albuminuria, start at 50 mg once daily and increase to the target dose of 100 mg once daily for maximum renoprotective benefit. 2, 4, 1

• Starting dose: 50 mg once daily 1
• Target dose: 100 mg once daily 2, 4, 1
• The proven renoprotective benefits in the RENAAL trial were achieved with 100 mg daily, not lower doses 2, 4

Pediatric Hypertension (Ages 6-16 Years)

• Starting dose: 0.7 mg/kg once daily (up to 50 mg total) 1
• Maximum dose: 1.4 mg/kg once daily (not to exceed 100 mg) 1
• Not recommended in children <6 years or with eGFR <30 mL/min/1.73 m² 1

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Dose Adjustments for Special Populations

Hepatic Impairment

In patients with mild-to-moderate hepatic impairment, start losartan at 25 mg once daily due to a 5-fold increase in plasma concentrations. 2, 1

• Losartan has not been studied in severe hepatic impairment and should be avoided 1

Renal Impairment

No dose adjustment is necessary for renal impairment unless the patient is also volume depleted; continue losartan even when eGFR falls below 30 mL/min/1.73 m² unless symptomatic hypotension or uncontrolled hyperkalemia develops. 4, 1

• Patients with renal insufficiency have elevated plasma concentrations but no routine dose adjustment is required 1
• Losartan is not removed by hemodialysis 3
• Accept up to 30% increase in serum creatinine within 4 weeks of initiation—this is expected and does not indicate harm 4

Elderly Patients (≥65 Years)

No dose adjustment is required based on age alone, but increase doses more gradually (every 2-4 weeks) in frail or very elderly patients (≥85 years) and monitor closely for orthostatic hypotension. 2, 1

• Measure blood pressure in both sitting and standing positions (after 5 minutes seated, then at 1 and 3 minutes after standing) before initiating or intensifying therapy 2
• Continue lifelong antihypertensive treatment beyond age 85 when well tolerated 2
• No overall differences in effectiveness or safety were observed in clinical trials 1

Volume-Depleted Patients

Start with 25 mg once daily in patients with possible intravascular depletion (e.g., on diuretic therapy) to minimize risk of first-dose hypotension. 1

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Contraindications

Absolute Contraindications

Losartan is absolutely contraindicated throughout pregnancy due to serious fetal toxicity including renal dysfunction, oligohydramnios, skull hypoplasia, and fetal death. 2, 1

• When pregnancy is detected, discontinue losartan immediately and switch to pregnancy-compatible antihypertensives (methyldopa, labetalol, or extended-release nifedipine) 2, 1
• Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death 1

Do not combine losartan with ACE inhibitors or direct renin inhibitors (aliskiren); dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2-3-fold without added cardiovascular benefit. 2, 4

• This combination is Class III: Harm per ACC/AHA guidelines 2
• The VALIANT trial demonstrated higher rates of adverse events without benefit 2

Relative Contraindications

• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney (losartan may cause acute renal failure in angiotensin-dependent renal function) 5
• Severe hepatic impairment (not studied) 1
• Hypersensitivity to losartan or any component 1

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Adverse Effects

Common Adverse Effects

Losartan is devoid of significant adverse effects and is better tolerated than many other antihypertensive agents, with a treatment-related adverse event rate of 19-27% similar to calcium channel blockers but lower than ACE inhibitors. 3, 6

• Dizziness and orthostatic hypotension: Especially in elderly or volume-depleted patients 2, 6
• Hyperkalemia: Monitor potassium levels, particularly in patients with CKD, diabetes, or on potassium-sparing agents 2, 4
• Renal dysfunction: Transient increases in serum creatinine (up to 30%) are expected and acceptable 4
• Upper respiratory infection: Similar to placebo 6

Serious Adverse Effects

• Acute renal failure: May occur in patients with bilateral renal artery stenosis, severe heart failure, or severe volume depletion 5
• Hyperkalemia: Particularly when combined with other RAAS blockers, potassium supplements, or potassium-sparing diuretics 2, 4
• Hypotension: Especially in volume-depleted patients 1

Advantages Over ACE Inhibitors

• Significantly lower incidence of cough: Cough occurred less often with losartan than with lisinopril or even hydrochlorothiazide 7
• No angioedema: No reports of angioedema in clinical trials 7
• Does not activate bradykinin-nitric oxide-prostanoid vasodilation (unlike ACE inhibitors) 7

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Monitoring Recommendations

Initial Monitoring

Check serum creatinine, eGFR, and potassium within 1-2 weeks after initiating losartan or increasing doses, especially in patients with diabetes, chronic kidney disease, or baseline low blood pressure. 2, 4

• Monitor blood pressure every 2-4 weeks during titration 2
• In elderly patients, measure blood pressure in both sitting and standing positions to detect orthostatic hypotension 2

Ongoing Monitoring

Monitor serum creatinine/eGFR and potassium at least annually during maintenance therapy, and more frequently (every 2-4 weeks) after dose changes. 2, 4

• Accept up to 30% increase in serum creatinine within 4 weeks—this is expected and does not indicate harm 4
• For diabetic nephropathy or CKD, monitor within 2-4 weeks after starting or changing dose 4
• Assess for symptomatic hypotension, especially in elderly or volume-depleted patients 4

Blood Pressure Targets

• General hypertension: <130/80 mmHg for most adults 2
• CKD patients: Office BP 130-139/80-90 mmHg for most; consider 120-129 mmHg systolic if tolerated for eGFR >30 mL/min/1.73 m² 4
• Aim to reach target within 3 months of therapy initiation 2

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Critical Safety Considerations and Common Pitfalls

Hyperkalemia Management

Don't stop losartan for mild hyperkalemia; implement potassium-lowering strategies (dietary restriction, diuretics, potassium binders) before reducing or stopping the medication. 2, 4

• The renoprotective and cardiovascular benefits often outweigh the risk of mild hyperkalemia 4
• KDIGO guidelines recommend managing hyperkalemia medically rather than stopping losartan when possible 4

Creatinine Increases

Don't stop losartan for mild creatinine increases (<30%); this is expected hemodynamic effect and does not indicate harm. 4

• Up to 30% increase in serum creatinine within 4 weeks is acceptable 4
• Continue losartan even when eGFR falls below 30 mL/min/1.73 m² for cardiovascular benefit 4

Underdosing

Don't underdose; the proven benefits in clinical trials were achieved with target doses of 100 mg daily for hypertension and diabetic nephropathy, and 100-150 mg daily for heart failure. 2, 4

• Less than 25% of patients are ever titrated to target doses in clinical practice 2
• Higher doses provide greater benefits than lower doses, with little evidence that medium-range doses approximate the benefits of target doses 2

Combination Therapy Errors

Never combine losartan with ACE inhibitors or aliskiren; this combination is contraindicated and increases adverse events without improving outcomes. 2, 4

• Also avoid triple RAAS blockade (ARB + ACE inhibitor + aldosterone antagonist) 2

Timing of Administration

Both morning and evening dosing are acceptable; there is no evidence that bedtime administration provides additional benefit over morning dosing. 2

• The American Diabetes Association states that preferential bedtime administration is not recommended 2
• The primary goal is sustained 24-hour blood pressure control 2

Race-Specific Considerations

In Black patients with hypertension and left ventricular hypertrophy, losartan may be less effective than atenolol for reducing cardiovascular events; the LIFE study provides no evidence that losartan's benefits apply to Black patients in this specific population. 1

• This finding was specific to the LIFE study population (hypertension with LVH) 1
• Blood pressure reductions were consistent between Black and non-Black patients 1

Pregnancy Detection

Perform serial ultrasound examinations if losartan must be continued during pregnancy (rare life-saving situations); if oligohydramnios is observed, discontinue immediately. 1

• Closely observe infants with in utero exposure for hypotension, oliguria, and hyperkalemia 1
• Exchange transfusion or dialysis may be required for neonatal hypotension or renal dysfunction 1

Adherence Optimization

Simplify regimens with once-daily dosing and single-pill combination products to enhance adherence. 2

• Before escalating therapy, assess medication adherence—non-adherence is a common cause of apparent treatment failure 2
• Don't assume discontinuation was due to side effects; directly question patients about cost, access, or misunderstanding 2