Introduction
Losartan is an angiotensin II receptor blocker (ARB) widely used in clinical practice for managing hypertension and other cardiovascular conditions. As the first commercially available ARB, it has established efficacy and safety profiles through extensive clinical use and research. This monograph provides comprehensive information about losartan for healthcare professionals and patients.
Mechanism of Action
Losartan selectively blocks the angiotensin II type 1 (AT1) receptors, preventing angiotensin II from binding to these receptors. Angiotensin II is a potent vasoconstrictor that also stimulates aldosterone secretion, promotes sodium and water retention, and contributes to vascular remodeling. By inhibiting these effects, losartan produces vasodilation, reduces peripheral resistance, decreases aldosterone-mediated fluid retention, and may provide organ-protective effects beyond blood pressure control.
Indications
- Hypertension (first-line therapy)
- Diabetic nephropathy with proteinuria in patients with type 2 diabetes
- Stroke risk reduction in patients with hypertension and left ventricular hypertrophy
- Off-label uses may include heart failure and renal protection in non-diabetic kidney disease
Dosage and Administration
Hypertension:- Initial dose: 25-50 mg once daily
- Maintenance dose: 25-100 mg once daily or divided twice daily
- Maximum dose: 100 mg daily
- Initial dose: 50 mg once daily
- May increase to 100 mg once daily based on blood pressure response
- Hepatic impairment: Initial dose 25 mg daily
- Renal impairment: No initial dosage adjustment needed, but monitor closely
- Geriatric patients: Consider starting with lower doses
- Pediatric patients (6 years and older): 0.7 mg/kg once daily (maximum 50 mg daily)
Pharmacokinetics
Absorption: Well absorbed orally with approximately 33% bioavailability Distribution: Volume of distribution ~34 liters; highly bound to plasma proteins (>98%) Metabolism: Hepatic metabolism via cytochrome P450 2C9 and 3A4 to active metabolite (EXP-3174) Elimination: Biliary and renal excretion; terminal half-life ~2 hours (losartan) and 6-9 hours (active metabolite) Onset of action: Within 1 hour; peak effect at 6 hours Duration: 24 hours for once-daily dosingContraindications
- Hypersensitivity to losartan or any component of the formulation
- Concomitant use with aliskiren in patients with diabetes
- Pregnancy (second and third trimesters)
- Severe hepatic impairment
Warnings and Precautions
Pregnancy: Category D in second and third trimesters - can cause fetal injury and death Renal impairment: Monitor renal function; may cause acute renal failure in susceptible patients Hyperkalemia: Risk increased in patients with renal impairment, diabetes, or using potassium-sparing diuretics Hypotension: May occur in volume-depleted patients Hepatic impairment: Use with caution; consider reduced dosing Renal artery stenosis: May worsen renal function Surgery/anesthesia: May potentiate hypotension effectsDrug Interactions
Significant interactions:- NSAIDs: May reduce antihypertensive effect and increase renal risk
- Potassium-sparing diuretics/potassium supplements: Increased hyperkalemia risk
- Lithium: Increased lithium levels and toxicity
- CYP2C9 inhibitors (fluconazole, amiodarone): May increase losartan levels
- Aliskiren: Contraindicated in diabetic patients
- Other antihypertensives: Additive hypotensive effects
Adverse Effects
Common (>1%):- Dizziness (3%)
- Upper respiratory infection (2%)
- Fatigue (1%)
- Cough (less than ACE inhibitors)
- Hyperkalemia
- Angioedema (rare)
- Hepatotoxicity
- Severe hypotension
- Acute renal failure
- Rhabdomyolysis
- Blood dyscrasias
Monitoring Parameters
- Blood pressure (regular measurements)
- Renal function (serum creatinine, BUN) at baseline and periodically
- Serum potassium levels, especially in high-risk patients
- Liver function tests in patients with hepatic impairment
- Pregnancy testing in women of childbearing potential
- Signs of angioedema or allergic reactions
- Volume status and electrolyte balance
Patient Education
- Take medication at the same time each day
- Do not stop taking abruptly without medical advice
- Report any signs of pregnancy immediately
- Monitor blood pressure regularly as directed
- Report persistent cough, swelling of face/lips, dizziness, or muscle pain
- Maintain regular follow-up appointments
- Avoid potassium supplements unless specifically prescribed
- Be cautious with over-the-counter NSAIDs
- Rise slowly from sitting/lying position to prevent dizziness
- Inform all healthcare providers about losartan use
References
1. FDA Prescribing Information for Losartan (2023) 2. 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. J Am Coll Cardiol. 2018 3. Brenner BM, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 4. Dahlöf B, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). Lancet. 2002 5. Micromedex Drug Information (2023) 6. Lexicomp Online (2023) 7. manufacturer's prescribing information
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.