losartan
Angiotensin II receptor blocker· Brands: Cozaar, Losar, Losartan PotassiumPO
Mechanism of action
Losartan is a selective, competitive antagonist at the angiotensin II type 1 (AT1) receptor. By blocking AT1 receptors, it prevents the vasoconstrictor and aldosterone-secreting effects of angiotensin II, leading to reduced peripheral resistance and sodium and water retention. This results in decreased blood pressure and reduced preload and afterload on the heart.
Pharmacokinetics
Losartan is well absorbed after oral administration, with an absolute bioavailability of about 33%. It undergoes extensive first-pass hepatic metabolism, primarily by CYP2C9 and CYP3A4, to form the active metabolite E-3174, which is 10 to 40 times more potent than losartan. Peak plasma concentrations occur 1 to 2 hours after a dose, and the active metabolite peaks at 3 to 4 hours. The elimination half-life of losartan is about 2 hours, while that of the active metabolite is 6 to 9 hours. Losartan and its metabolites are excreted in urine and bile, and clearance is reduced in hepatic impairment.
Indications & dosing
Hypertension
Initial dose 50 mg once daily; may be increased to a maximum of 100 mg once daily. Consider 25 mg initial dose in volume-depleted patients.
- adult · PO: 50–100 mg OD · Initial dose 50 mg once daily; may be increased to a maximum of 100 mg once daily. Consider 25 mg initial dose in volume-depleted patients.
Heart failure (in patients intolerant to ACE inhibitors)
Initial dose 50 mg once daily, titrate to target 150 mg once daily as tolerated.
- adult · PO: 50–150 mg OD · Initial dose 50 mg once daily, titrate to target 150 mg once daily as tolerated.
Diabetic kidney disease in type 2 diabetes
Used to reduce the progression of nephropathy and cardiovascular risk.
- adult · PO: 50–100 mg OD · Used to reduce the progression of nephropathy and cardiovascular risk.
Hypertension in children and adolescents
Initial dose 0.7 mg/kg once daily, may be increased to 1.4 mg/kg once daily (maximum 100 mg).
- pediatric · PO: 0.7–1.4 mg/kg OD · Initial dose 0.7 mg/kg once daily, may be increased to 1.4 mg/kg once daily (maximum 100 mg).
Contraindications & precautions
- Pregnancy (especially second and third trimester) · Risk of fetal renal damage and death; stop if pregnancy occurs.
- Bilateral renal artery stenosis · Risk of acute renal failure.
- Concurrent use with aliskiren in diabetes or renal impairment · Increased risk of hyperkalaemia, hypotension and renal impairment.
- Hypersensitivity to losartan · Rare but severe reactions.
- Monitor serum potassium and renal function, especially in patients with renal disease or on potassium-sparing drugs.
- Correct volume depletion before initiation to reduce risk of symptomatic hypotension.
- Avoid during pregnancy; use effective contraception in women of childbearing potential.
- Use caution in patients with hepatic impairment as losartan is metabolised to active metabolite.
- Caution in patients with primary aldosteronism as response may be suboptimal.
Adverse effects
- Hyperkalaemiaserious
- Hypotensionserious
- Dizziness
- Fatigue
- Angioedemaserious
- Renal impairmentserious
- Cough
- Headache
Interactions
- ramiprilmajorAvoid the combination unless there is a compelling indication and specialist input. If used, initiate with close monitoring of serum potassium, creatinine, and blood pressure at baseline, then within 1 to 2 weeks of starting or dose adjustment, and periodically thereafter. Discontinue one agent if hyperkalaemia, significant hypotension, or worsening renal function occurs. Due to the lack of clear benefit for most indications, this combination is not recommended routinely.
Renal & hepatic adjustment
- eGFR 30–300: No dosage adjustment required for mild to moderate renal impairment (eGFR ≥ 30 mL/min).
- eGFR 0–29: Use with caution in severe renal impairment (eGFR < 30 mL/min). Consider a lower starting dose (e.g., 25 mg once daily) and monitor renal function and serum potassium. No adjustment needed for patients on dialysis.
- Hepatic impairment (mild): Reduce initial dose to 25 mg once daily in mild hepatic impairment. Titrate slowly and monitor response.
- Hepatic impairment (moderate): Reduce initial dose to 25 mg once daily in moderate hepatic impairment. Monitor closely for adverse effects.
- Hepatic impairment (severe): Avoid use in severe hepatic impairment (Child-Pugh C). (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Before and after initiation, then periodically during treatment
- Serum potassium · At baseline, 1-2 weeks after starting, then periodically
- Serum creatinine and eGFR · At baseline, 1-2 weeks after starting, then periodically
- Signs of angioedema · Monitor during treatment
- Pregnancy: Losartan is contraindicated in pregnancy. Discontinue treatment immediately if pregnancy is detected. Use of ARBs during the second and third trimesters can cause fetal renal damage, oligohydramnios, and fetal death. If there is a need for antihypertensive therapy in pregnancy, consider safer alternatives such as methyldopa, labetalol, or nifedipine.
- Toxicity: Hypotension, tachycardia, and dizziness are the most common features of overdose. · Provide supportive care. Place patient in supine position and give intravenous fluids. If needed, use vasopressors to maintain blood pressure. Monitor renal function and electrolytes.
- Toxicity: Hyperkalaemia may occur, especially in patients with renal impairment or concurrent potassium-sparing agents. · Monitor serum potassium closely. In severe hyperkalaemia, treat with intravenous calcium gluconate, insulin-glucose infusion, and other potassium-lowering measures.
- Toxicity: Acute kidney injury can occur due to prolonged hypotension or direct nephrotoxicity. · Ensure adequate volume resuscitation and monitor renal function. Consider renal replacement therapy if renal failure develops.
- Toxicity: Angioedema, including symptoms such as tongue or throat swelling, may occur rarely. · Discontinue losartan immediately and provide emergency airway management if necessary. Administer epinephrine, antihistamines, and corticosteroids as appropriate.
Clinical notes
Losartan is used to treat hypertension, heart failure, and diabetic nephropathy. It is also indicated to reduce the risk of stroke in patients with left ventricular hypertrophy. It is contraindicated in pregnancy, bilateral renal artery stenosis, and in patients with a history of angioedema. Monitor serum potassium, creatinine, and blood pressure periodically. Use with caution in patients with hepatic impairment or volume depletion. Common adverse effects include dizziness, headache, and hyperkalaemia. As with other ARBs, avoid concurrent use with aliskiren in patients with diabetes.
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BNF; local formulary