LOSARTAN POTASSIUM
Clinical safety rating: avoid
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
Angiotensin II receptor antagonist. Blocks the binding of angiotensin II to AT1 receptors in vascular smooth muscle and adrenal gland, resulting in vasodilation and reduced aldosterone secretion.
| Metabolism | Hepatic via CYP2C9 and CYP3A4; active metabolite E-3174 formed via CYP2C9. |
| Excretion | Losartan and its active metabolite E-3174 are eliminated via renal (35% of dose) and biliary/fecal (60% of dose) routes. Approximately 4% of an oral dose is excreted unchanged in urine, while 6% is excreted as E-3174 in urine. |
| Half-life | Terminal elimination half-life: losartan ~2 hours; active metabolite E-3174 ~6-9 hours. Clinically, the long half-life of E-3174 allows once-daily dosing. |
| Protein binding | Losartan is >99% bound to plasma proteins, primarily albumin; E-3174 is >99.9% bound. |
| Volume of Distribution | Losartan: ~34 L (0.47 L/kg for a 70 kg adult); E-3174: ~12 L (0.17 L/kg). Vd suggests distribution primarily into extracellular fluid. |
| Bioavailability | Oral bioavailability: ~33% (range 25-35%) due to extensive first-pass metabolism. IV administration yields 100% bioavailability. |
| Onset of Action | Oral: Within 1 hour, with peak effect at 3-6 hours. IV: Onset within minutes. |
| Duration of Action | 24 hours (supports once-daily dosing); antihypertensive effect persists for 24 hours with chronic dosing. |
| Molecular Weight | 461 |
50 mg orally once daily; may increase to 100 mg once daily based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | No adjustment for GFR ≥30 mL/min/1.73m²; not recommended for GFR <30 mL/min (no data). |
| Liver impairment | Contraindicated in Child-Pugh C cirrhosis; use lower starting dose (25 mg once daily) in Child-Pugh A or B. |
| Pediatric use | Weight-based: 0.7 mg/kg once daily, up to 50 mg; titrate to maximum 1.4 mg/kg (not exceeding 100 mg) once daily. |
| Geriatric use | Start at 25 mg once daily; may titrate based on response, with careful monitoring for hypotension and renal function. |
| 1st trimester | Contraindicated: risk of fetal renal impairment, oligohydramnios, and skull ossification defects; alternative antihypertensive preferred. |
| 2nd trimester | Contraindicated: exposure associated with fetal oligohydramnios, renal dysfunction, and pulmonary hypoplasia. |
| 3rd trimester | Contraindicated: exposure increases risk of neonatal hypotension, anuria, hyperkalemia, and death due to severe oligohydramnios. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Use in pregnancy can cause injury and death to the developing fetus.
| FDA category | Contraindicated |
| Placental transfer | Losartan crosses the placenta. Animal studies demonstrate placental transfer; human data show measurable fetal concentrations and adverse fetal effects when used in pregnancy. |
■ FDA Black Box Warning
None
| Common Effects | Dizziness Decreased blood pressure Hypoglycemia low blood glucose level Increased potassium level in blood Increased blood urea |
| Serious Effects |
Hypersensitivity to losartan or any componentPregnancy (especially second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus
| Precautions | Fetal/neonatal morbidity and death when used in pregnancy during second and third trimesters, Hypotension in volume-depleted patients, Renal function deterioration, especially in renal artery stenosis, Hyperkalemia, especially in renal impairment or with K+-sparing diuretics |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, potatoes, tomatoes, spinach, avocados, dried fruits) in large amounts. Avoid salt substitutes containing potassium chloride. Grapefruit juice does not significantly interact. Alcohol may enhance hypotensive effects. |
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| Breastfeeding |
| Losartan potassium is excreted into breast milk in small amounts; based on limited data, it is considered compatible with breastfeeding. Monitor infant for hypotension, hyperkalemia, and renal function. |
| Lactation Rating | L2 (Limited data - Probably Compatible) |
| Teratogenic Risk | First trimester: Limited data suggest potential risk of congenital anomalies; second and third trimesters: Known to cause fetal renal dysfunction, oligohydramnios, skull ossification defects, and neonatal renal failure; use contraindicated in pregnancy, especially after 20 weeks. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, potassium), and fetal ultrasound for oligohydramnios if inadvertent exposure; discontinue immediately if pregnancy detected. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment of fertility at therapeutic doses. |
| Clinical Pearls | Monitor serum potassium and renal function within 2-4 weeks of initiation and periodically thereafter. Avoid use in pregnancy, especially during second and third trimesters. Can be used with or without food. Dose adjustment needed in hepatic impairment. Bilateral renal artery stenosis is a contraindication. May cause angioedema, though rare. Use cautiously with NSAIDs as they may reduce efficacy and increase risk of renal impairment. |
| Patient Advice | Take exactly as prescribed, usually once daily. · Avoid potassium supplements or salt substitutes containing potassium unless approved by your doctor. · Report symptoms such as dizziness, fainting, or swelling of face/lips immediately. · Do not use if pregnant or planning pregnancy; discuss effective contraception. · May cause dizziness; avoid driving until you know how the drug affects you. · Do not stop abruptly without consulting your doctor. |