COZAAR
Clinical safety rating
cautionComprehensive clinical and safety monograph for COZAAR (COZAAR).
Losartan is a selective angiotensin II receptor type 1 (AT1) antagonist. It blocks the binding of angiotensin II to AT1 receptors in vascular smooth muscle and adrenal gland, leading to vasodilation, reduced aldosterone secretion, and decreased blood pressure. It also reduces proteinuria and slows progression of renal disease by decreasing intraglomerular pressure.
| Metabolism | Losartan is extensively metabolized in the liver via CYP2C9 and CYP3A4 to its active metabolite, E-3174, which is more potent than the parent drug. E-3174 is further metabolized to inactive metabolites. Both losartan and E-3174 are excreted in urine and feces. |
| Excretion | Renal (35% as unchanged drug and 18% as active metabolite), biliary/fecal (approximately 60% of radiolabeled dose recovered in feces) |
| Half-life | Plasma half-life of losartan: approximately 2 hours; active metabolite E-3174: 6–9 hours. Clinical context: once-daily dosing due to prolonged receptor blockade by metabolite |
| Protein binding | ≥99% (primarily albumin); losartan ≥98.7%, active metabolite ≥99.8% |
| Volume of Distribution | Losartan: 34 L (0.47 L/kg for 70 kg adult); active metabolite: 12 L. Indicates limited extravascular distribution |
| Bioavailability | Oral: about 33% (losartan); active metabolite bioavailability not directly reported but formed via first-pass metabolism |
| Onset of Action | Oral: 1 hour (peak antihypertensive effect at 3–6 hours) |
| Duration of Action | 24 hours (supports once-daily dosing); maximal effect at 3–6 weeks of therapy |
| Molecular Weight | 461.01 Da |
50 mg orally once daily; may increase to 100 mg once daily based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; for GFR <30 mL/min, initial dose is 25 mg orally once daily. |
| Liver impairment | For Child-Pugh Class A or B: initial dose is 25 mg orally once daily; no data for Class C. |
| Pediatric use | For children ≥6 years: initial dose 0.7 mg/kg (up to 50 mg) orally once daily; maximum 1.4 mg/kg (up to 100 mg) once daily. |
| Geriatric use | Consider lower initial dose of 25 mg orally once daily due to potential for volume depletion or decreased renal function. |
| 1st trimester | Contraindicated: Risk of fetal renal dysfunction, oligohydramnios, and skull ossification defects. Avoid use in first trimester unless no alternative. |
| 2nd trimester | Contraindicated: Known to cause fetal renal impairment, oligohydramnios, and potential neonatal complications. Avoid use. |
| 3rd trimester | Contraindicated: Direct renin-angiotensin system (RAS) blockade can cause fetal renal failure, oligohydramnios, and skull hypoplasia. Highest risk. |
Clinical note
Comprehensive clinical and safety monograph for COZAAR (COZAAR).
| Placental transfer | Losartan and its active metabolite cross the placenta in humans. Evidence of fetal toxicity and teratogenicity, especially in second and third trimesters. |
| Breastfeeding | Losartan is excreted into breast milk in low concentrations. Due to the theoretical risk of renal effects in nursing infants, especially premature or hypotensive infants, use during breastfeeding is generally not recommended. Consider alternative agents. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Contraindicated in pregnancy. First trimester: Associated with congenital malformations, including renal dysplasia and oligohydramnios. Second and third trimesters: Fetal toxicity (oligohydramnios, pulmonary hypoplasia, skull ossification defects, neonatal anuria, hypotension, and death). |
| Fetal Monitoring | Monitor fetal ultrasound (amniotic fluid index, renal function) if inadvertent exposure; assess neonatal blood pressure and renal function post-delivery. |
| Fertility Effects | No specific human data; theoretical risk of altered renin-angiotensin system affecting reproductive function; no definitive evidence of impaired fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Concomitant use with aliskiren in patients with diabetesHistory of hypersensitivity to losartan or any componentPregnancy
| Precautions | Fetal toxicity (discontinue when pregnancy is detected); hypotension in volume-depleted patients; renal impairment (monitor serum creatinine and potassium); hyperkalemia; angioedema; dual blockade of renin-angiotensin system (increased risk of hypotension, hyperkalemia, renal dysfunction); hepatotoxicity; monitor for azotemia in renovascular hypertension. |
| Food/Dietary | No significant food interactions. However, avoid high-potassium foods (such as bananas, oranges, leafy greens, tomatoes, and avocados) in large amounts if taken with potassium supplements or if renal function is impaired. Limit salt intake as advised for hypertension management. Grapefruit juice does not interact significantly with losartan. |
| Clinical Pearls | Cozaar (losartan) is an angiotensin II receptor blocker (ARB). Monitor renal function and electrolytes, especially potassium, within 2-4 weeks of initiation and periodically thereafter. May cause a reversible rise in serum creatinine, especially in renal artery stenosis. Has a uricosuric effect, modestly lowering uric acid levels. Avoid use in pregnancy (category D). Dose adjustment recommended for hepatic impairment. Can be used as an alternative in patients who develop ACE-inhibitor-induced cough. |
| Patient Advice | Take once daily with or without food; consistency in timing is key. · Avoid potassium supplements or salt substitutes containing potassium unless directed by your doctor. · May cause dizziness, especially at start; avoid driving until you know how it affects you. · Do not use if pregnant, planning pregnancy, or breastfeeding; discuss contraception with your doctor. · Report symptoms like fainting, rapid heartbeat, or leg swelling to your doctor. · Stay well-hydrated, especially if you experience diarrhea or vomiting, as dehydration can worsen side effects. · Do not stop this medication abruptly; consult your physician before discontinuing. |
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