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Losartan

Losartan

Cozaar Hyzaar (combination with hydrochlorothiazide)

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Updated: December 06, 2025

Overview

Losartan is an angiotensin II receptor blocker (ARB) used primarily for the treatment of hypertension. It works by selectively blocking the binding of angiotensin II to AT1 receptors, resulting in vasodilation, reduced aldosterone secretion, and decreased blood pressure. Losartan offers advantages over ACE inhibitors by not causing cough as a common side effect and may provide renal protective effects in patients with diabetic nephropathy. First approved by the FDA in 1995, losartan is also indicated for reducing stroke risk in hypertensive patients with left ventricular hypertrophy and slowing the progression of diabetic nephropathy. It demonstrates a favorable safety profile with once-daily dosing and is often used as first-line therapy for hypertension, particularly in patients who cannot tolerate ACE inhibitors.

Drug Class

Therapeutic category: Antihypertensive Pharmacologic class: Angiotensin II receptor blocker (ARB), selective AT1 receptor antagonist

Mechanism of Action

Losartan competitively inhibits the binding of angiotensin II to the AT1 receptor subtype found in vascular smooth muscle, adrenal glands, and other tissues. By blocking AT1-mediated vasoconstriction and aldosterone release, it causes: • Vasodilation of arterioles • Reduced sodium and water reabsorption • Decreased sympathetic nervous system activation • Inhibition of cardiac and vascular remodeling

Pharmacokinetics

Absorption: Oral bioavailability ~33%. Food delays absorption but doesn't significantly affect AUC. Peak plasma concentration in 1 hour. Distribution: Volume of distribution 34L. 99% protein-bound (mainly albumin). Crosses blood-brain barrier minimally. Metabolism: Hepatic via CYP2C9 (major) and CYP3A4 to active metabolite E-3174 (10-40 times more potent than parent drug). Excretion: Renal (35% as metabolites) and fecal (60% as unchanged drug). Half-life: Losartan: 2 hours. Active metabolite E-3174: 6-9 hours.

Pharmacodynamics

• Dose-dependent blood pressure reduction within 6 hours, lasting 24 hours • Increases renal blood flow without significant glomerular filtration rate changes • Reduces urinary protein excretion in diabetic nephropathy • Decreases left ventricular mass in hypertensive patients with LVH • Uric acid excretion increased by ~30%

Indications

• Hypertension: Management of essential hypertension (monotherapy or combination) • Diabetic Nephropathy: Treatment of proteinuria in type 2 diabetes with hypertension • Stroke Risk Reduction: Reduction of stroke risk in hypertensive patients with left ventricular hypertrophy • Off-label: Heart failure management (when ACE inhibitors not tolerated)

Contraindications

Absolute: • Hypersensitivity to losartan or any component • Pregnancy (second and third trimesters) • Concomitant use with aliskiren in diabetic patients Relative: • Bilateral renal artery stenosis • Severe hepatic impairment (Child-Pugh C) • Volume depletion or hyponatremia • Aortic or mitral valve stenosis

Dosage & Administration

Hypertension: Initial dose 50mg once daily. May increase to 100mg daily. Maximum dose: 100mg/day. Diabetic Nephropathy: Initial dose 50mg once daily. May increase to 100mg daily based on blood pressure response. Hypertension with LVH: Initial dose 50mg daily. Add hydrochlorothiazide 12.5mg daily or increase losartan to 100mg daily. Volume-depleted patients: Start with 25mg once daily.

Special Populations

Pediatric: ≥6 years: 0.7mg/kg once daily (max 50mg). Adjust based on response. Geriatric: No initial dose adjustment needed. Monitor for orthostatic hypotension. Renal impairment: No initial dose adjustment for mild-moderate impairment (CrCl >30mL/min). Use caution in severe impairment (CrCl <30mL/min). Hepatic impairment: Initial dose 25mg daily in moderate-severe impairment.

Adverse Effects

Common (>10%): • Dizziness (8-14%) • Upper respiratory infection (6-14%) • Hyperkalemia (10% in diabetic nephropathy patients) • Fatigue (3-4%) Serious (<1%): • Angioedema (0.1%) • Acute renal failure • Hypotension (especially in volume-depleted patients) • Hepatotoxicity (rare) • Rhabdomyolysis (rare)

Drug Interactions

• NSAIDs: Reduced antihypertensive effect; increased risk of renal impairment • Potassium supplements/potassium-sparing diuretics: Increased risk of hyperkalemia • Lithium: Increased lithium levels (monitor serum lithium) • CYP2C9 inhibitors (fluconazole): Increase losartan levels • Rifampin: Decreases active metabolite levels

Warnings & Precautions

• Fetal Toxicity: Discontinue immediately if pregnancy detected (risk of fetal injury/death) • Hypotension: Risk in volume-depleted patients (correct volume status first) • Hyperkalemia: Monitor serum potassium, especially in renal impairment or diabetes • Renal Function: Monitor in renal artery stenosis and heart failure patients • Hepatic Impairment: Use lower starting doses

Pregnancy & Lactation

Pregnancy: FDA Category D (second/third trimesters). Contraindicated in pregnancy due to risk of fetal harm. Discontinue immediately if pregnancy detected. Lactation: Losartan and metabolites excreted in breast milk. Avoid breastfeeding. Consider alternative antihypertensives.

Monitoring Parameters

• Blood pressure (regular monitoring) • Serum creatinine and BUN (baseline and periodic) • Serum potassium (especially in renal impairment, diabetes, or with potassium supplements) • Urinary protein in diabetic nephropathy • Liver function tests (if hepatic impairment suspected) • Signs of angioedema

Patient Counseling

• Take consistently once daily, with or without food • Report pregnancy immediately if suspected • Maintain adequate fluid intake unless contraindicated • Avoid potassium supplements/salt substitutes unless prescribed • Rise slowly to prevent dizziness • Report signs of allergic reaction (swelling, difficulty breathing) • Do not discontinue without medical advice

Storage & Stability

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from light. Keep bottle tightly closed. Discard unused portions after expiration date.

Clinical Pearls

• First ARB approved for renal protection in diabetic nephropathy • Preferred over ACE inhibitors in patients with ACE inhibitor-induced cough • More uricosuric effect than other ARBs • Consider lower starting doses in Asian patients (increased sensitivity) • Takes 3-6 weeks for full renal protective effects in nephropathy • Can be used as alternative to ACE inhibitors in heart failure patients

References

• Micromedex Solutions: Losartan Drug Information • UpToDate: Losartan: Drug information • FDA Prescribing Information: Cozaar (2023) • Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults • Brenner & Rector's The Kidney, 11th Edition