Clinical safety rating: avoid
Contraindicated (not allowed)
Losartan is an angiotensin II receptor blocker (ARB) that selectively and competitively inhibits the binding of angiotensin II to the AT1 receptor, thereby antagonizing vasoconstriction, aldosterone secretion, and renal sodium reabsorption, leading to reduced blood pressure.
| Metabolism | Losartan undergoes hepatic metabolism primarily via CYP2C9 and CYP3A4 to its active metabolite E-3174, which is more potent and has a longer half-life. Both losartan and E-3174 are further metabolized and excreted primarily in bile and urine. |
| Excretion | Renal: 50% (parent drug and active metabolite), Biliary/Fecal: 50% |
| Half-life | Terminal half-life: 6-9 hours (losartan), 6-9 hours (active metabolite E-3174); clinical context: once-daily dosing is sufficient due to prolonged receptor binding |
| Protein binding | 99.7% bound to albumin (losartan), 99.8% (E-3174); primarily albumin, alpha-1-acid glycoprotein minor |
| Volume of Distribution | 34 L (0.49 L/kg) for losartan; 12 L (0.17 L/kg) for E-3174; indicates distribution mainly into extracellular fluid |
| Bioavailability | Oral: 33% (losartan); active metabolite E-3174: 25% (systemic exposure 4-8 times greater than parent) |
| Onset of Action | Oral: 1-2 hours (peak antihypertensive effect at 3-6 hours) |
| Duration of Action | 24 hours (supports once-daily dosing); note: antihypertensive effect may persist up to 48 hours after multiple doses |
| Molecular Weight | 461 |
Losartan 50 mg orally once daily; may increase to 100 mg once daily based on blood pressure response.
| Renal impairment | For GFR <30 mL/min/1.73 m²: initial dose of 25 mg orally once daily; no adjustment needed for GFR ≥30 mL/min/1.73 m². |
| Liver impairment | For Child-Pugh class B or C: initial dose of 25 mg orally once daily. |
| Pediatric use | For children ≥6 years and <20 kg: initial 0.7 mg/kg (up to 25 mg) orally once daily; for ≥20 kg: initial 25 mg orally once daily; may increase to total 1.4 mg/kg (up to 100 mg) once daily. |
| Geriatric use | Consider starting at 25 mg orally once daily in patients >75 years to reduce risk of hypotension; monitor renal function and electrolytes. |
| 1st trimester | Use is not recommended during the first trimester due to potential risk of fetal nephrotoxicity and oligohydramnios; based on animal data and limited human data, alternative agents with established safety profiles are preferred. |
| 2nd trimester | Contraindicated in the second trimester due to fetal renal toxicity, oligohydramnios, skull ossification defects, and neonatal morbidity; discontinue immediately if pregnancy is detected. |
| 3rd trimester | Contraindicated in the third trimester due to the same risks as the second trimester, including oligohydramnios and neonatal hypotension, hyperkalemia, and renal failure. |
Clinical note
Contraindicated throughout pregnancy. ARBs carry the same fetopathic mechanism as ACE inhibitors: inhibition of the renin-angiotensin system (RAS) disrupts fetal renal development. Second and third trimester exposure causes fetal renal tubular dysgenesis, oligohydramnios, skull hypoplasia, limb contractures, and fetal/neonatal death. First-trimester risk for cardiac defects has been reported. Discontinue immediately upon confirmed pregnancy.
| Placental transfer | Losartan crosses the placenta. Molecular evidence from animal studies and human case reports confirm transfer, with fetal exposure reaching maternal levels. The active metabolite EXP3174 likely also transfers, contributing to fetotoxicity. |
■ FDA Black Box Warning
Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Serious Effects |
Hypersensitivity to losartan or any componentConcomitant aliskiren use in patients with diabetes mellitus or renal impairment (eGFR <60 mL/min/1.73 m²)Pregnancy (second and third trimester)
| Precautions | Hypotension in volume-depleted patients, Renal function impairment (especially in bilateral renal artery stenosis), Hyperkalemia (monitor serum potassium), Monitor renal function and electrolytes periodically, Avoid use with aliskiren in patients with diabetes (increases risk of renal impairment, hypotension, hyperkalemia) |
| Food/Dietary | Avoid salt substitutes containing potassium chloride. No significant food interactions, but consistent timing with meals may reduce minor GI upset. Grapefruit juice has no significant interaction. |
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| Breastfeeding | Losartan is excreted into human breast milk in small amounts (~1 μg/L with milk/plasma ratio <1). Consider the benefits of breastfeeding and the mother's need for losartan; if used, monitor the infant for hypotension and renal effects. Alternative antihypertensives with more data (e.g., labetalol, nifedipine) may be preferred. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Increased risk of fetal renal anomalies and oligohydramnios. Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria. Contraindicated in pregnancy. |
| Fetal Monitoring | Monitor fetal renal function, amniotic fluid volume (ultrasound), and fetal growth. Maternal blood pressure and renal function (serum creatinine, potassium). |
| Fertility Effects | No known direct impairment of fertility. However, angiotensin II receptor antagonists like losartan may affect fertility in animal studies. Clinical significance unknown. |
| Clinical Pearls | Losartan is an angiotensin II receptor blocker (ARB) used primarily for hypertension and nephropathy in type 2 diabetes. Monitor renal function and serum potassium, especially in patients with renal impairment or those on potassium-sparing diuretics. Avoid in pregnancy. Dose adjustment may be needed in hepatic impairment. Onset is gradual over 2-4 weeks. |
| Patient Advice | Take exactly as prescribed, usually once daily. · Avoid potassium supplements or salt substitutes containing potassium unless advised by your doctor. · Report symptoms of dizziness, fainting, or swelling of the face/lips immediately. · Do not stop taking without consulting your doctor even if you feel well. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Stay hydrated but avoid dehydration from excessive sweating or diarrhea. |