COZAAR
Clinical safety rating: caution
Comprehensive 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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COZAAR (COZAAR).
| Breastfeeding | Not recommended. No data on M/P ratio; excreted in rat milk; potential for adverse effects in nursing infant due to renin-angiotensin system blockade. |
| 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 |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to losartan or any component; pregnancy (especially second and third trimesters); concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (eGFR <60 mL/min/1.73m²); history of angioedema related to previous ARB therapy.
| 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. |
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| 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. |