ZOFRAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOFRAN (ZOFRAN).
Selective serotonin 5-HT3 receptor antagonist; blocks serotonin binding at 5-HT3 receptors in the chemoreceptor trigger zone and gastrointestinal tract, thereby inhibiting emesis.
| Metabolism | Metabolized primarily by hepatic cytochrome P450 enzymes: CYP1A1, CYP1A2, CYP2D6, and CYP3A4. Less than 5% excreted unchanged in urine. |
| Excretion | Approximately 5% of the dose is excreted unchanged in urine; the remainder undergoes extensive hepatic metabolism via CYP1A1, CYP1A2, CYP3A4, and flavin-containing monooxygenases, with metabolites excreted in urine (about 44-60% of total clearance) and feces (about 25-45%). Less than 10% is eliminated in bile. |
| Half-life | Terminal elimination half-life is approximately 3-4 hours in adults; in children (1 month to 12 years), half-life averages 2.5 hours; in elderly (≥75 years), half-life may be prolonged to 5.5 hours. Clinically, repeated dosing every 8 hours maintains antiemetic coverage. |
| Protein binding | Plasma protein binding is 70-76%, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 2.2-2.5 L/kg (140-160 L in a 70 kg adult). This indicates extensive extravascular distribution, consistent with good penetration into cerebrospinal fluid (CSF:plasma ratio ~0.5-0.6). |
| Bioavailability | Oral bioavailability is approximately 60% (range 50-70%) due to first-pass metabolism; intramuscular bioavailability is ~100%; rectal bioavailability is about 50-60%. |
| Onset of Action | Intravenous: onset within 1-2 minutes; oral (tablet or orally disintegrating tablet): onset within 30-60 minutes; intramuscular: onset within 10-15 minutes. Peak effect typically occurs at time to Cmax: oral 1-2 hours, IV immediate, IM ~15 minutes. |
| Duration of Action | Duration of antiemetic effect ranges from 4-12 hours depending on dose and route. IV 4 mg typically provides effect for 4-8 hours; oral 8 mg may last 8-12 hours. Clinical context: Used for prevention of chemotherapy-induced nausea/vomiting (CINV) and postoperative nausea/vomiting (PONV), with dosing every 8 hours for CINV. |
8 mg orally or intravenously 30 minutes before chemotherapy; may repeat 8 mg orally 8 hours after first dose, then 8 mg orally every 12 hours for 1-2 days.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, dosing interval should be increased to every 24 hours. |
| Liver impairment | Child-Pugh A or B: No dose adjustment. Child-Pugh C: Maximum daily dose of 8 mg (single dose). |
| Pediatric use | 0.15 mg/kg/dose intravenously 30 minutes before chemotherapy, maximum 16 mg per dose. Or 4 mg (≥12 years) or 0.1 mg/kg (4-11 years) orally every 12 hours. |
| Geriatric use | No specific dose adjustment; pharmacokinetics similar to younger adults; caution with hepatic or renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOFRAN (ZOFRAN).
| Breastfeeding | Ondansetron is excreted into breast milk in low amounts (M/P ratio ~0.1-0.2). Relative infant dose is approximately 0.5-1% of maternal weight-adjusted dose. No adverse effects reported in breastfed infants. American Academy of Pediatrics considers ondansetron compatible with breastfeeding. |
| Teratogenic Risk | Ondansetron (Zofran) is not associated with a significant increase in major congenital malformations based on large cohort studies. First trimester use shows no clear increase in orofacial clefts (RR 1.1, 95% CI 0.9-1.3). Second and third trimester risks are minimal; no specific fetal adverse effects documented. However, some studies suggest slight increase in cardiac defects (RR 1.3, 95% CI 0.99-1.7), but causality not established. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to ondansetron or any component of the formulation","Concomitant use with apomorphine (may cause profound hypotension and loss of consciousness)"]
| Precautions | ["Risk of QT prolongation, especially with electrolyte abnormalities, congestive heart failure, or concomitant use of other QT-prolonging drugs","Serotonin syndrome risk, particularly with concomitant serotonergic drugs","Hypersensitivity reactions including anaphylaxis","Masking of progressive ileus or gastric distension after abdominal surgery"] |
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| Fetal Monitoring | No specific fetal monitoring required. Maternal ECG monitoring if prolonged use or QT interval concerns (ondansetron may cause QT prolongation). Monitor for serotonin syndrome if used with other serotonergic drugs. |
| Fertility Effects | No known adverse effects on human fertility. Preclinical studies show no impairment of fertility in rats at doses up to 15 mg/kg/day. |