ZOFRAN ODT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOFRAN ODT (ZOFRAN ODT).
Selective antagonist of serotonin 5-HT3 receptors, blocking serotonin binding in the chemoreceptor trigger zone and gastrointestinal tract, thereby inhibiting emesis.
| Metabolism | Hepatic via CYP1A2, CYP2D6, and CYP3A4 |
| Excretion | Renal (47% as unchanged drug and metabolites, primarily glucuronide conjugates) and hepatic metabolism; about 25% excreted in feces; less than 10% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life approximately 3–6 hours in adults; prolonged to 8–15 hours in patients with severe hepatic impairment (Child-Pugh C) due to reduced clearance. |
| Protein binding | 70–76% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Volume of distribution 1.7–2.5 L/kg; wide distribution suggests extensive tissue binding. |
| Bioavailability | Oral bioavailability approximately 60% due to first-pass metabolism; bioavailability of ODT formulation is similar to conventional oral tablet (~60% relative to IV). |
| Onset of Action | Orally disintegrating tablet: Onset of antiemetic effect within 30 minutes to 2 hours; peak plasma concentration at 1–2 hours. |
| Duration of Action | Duration of antiemetic effect approximately 12–24 hours; clinical trials show efficacy for prevention of chemotherapy-induced nausea and vomiting for up to 24 hours after dosing. |
8 mg orally disintegrating tablet (ODT) 30 minutes before chemotherapy; for prevention of nausea/vomiting, 8 mg orally twice daily.
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), maximum daily dose of 8 mg. |
| Liver impairment | Severe hepatic impairment (Child-Pugh C): maximum total daily dose of 8 mg. |
| Pediatric use | For chemotherapy-induced nausea/vomiting: 0.15 mg/kg/dose IV (max 16 mg) 30 minutes before chemotherapy, then every 4 hours as needed. For radiation-induced: weight ≥30 kg: 8 mg ODT 1-2 hours before radiation; weight <30 kg: 4 mg ODT. For postoperative nausea/vomiting: 0.1 mg/kg IV (max 4 mg) at induction. |
| Geriatric use | No specific dose adjustment; use caution in elderly due to potential QT prolongation risk, and consider reduced starting doses if renal or hepatic function is compromised. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOFRAN ODT (ZOFRAN ODT).
| Breastfeeding | Ondansetron is excreted into human breast milk in low amounts. The estimated infant dose is approximately 4-5% of the maternal weight-adjusted dose. The milk-to-plasma ratio is not well established. Caution is advised due to potential for adverse effects in the infant (e.g., QT prolongation, serotonin syndrome). Consider risks versus benefits. |
| Teratogenic Risk | Ondansetron (Zofran ODT) is classified as FDA Pregnancy Category B. Large cohort studies do not show a statistically significant increased risk of major congenital malformations overall. Some studies suggest a possible small increased risk of cleft palate (odds ratio ~1.24) when used in the first trimester, but data are conflicting. No consistent evidence of other malformations. Second and third trimester use is not associated with structural defects. Risk of preterm birth or low birth weight not clearly increased. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to ondansetron or any component of the formulation; concomitant use with apomorphine (risk of severe hypotension and loss of consciousness)
| Precautions | Serotonin syndrome when used with other serotonergic drugs; QT prolongation (dose-dependent); masked progressive ileus/gastric distension; hypersensitivity reactions; use in patients with hepatic impairment may require dose adjustment |
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| Fetal Monitoring | Monitor maternal ECG if risk factors for QT prolongation (e.g., electrolyte abnormalities, concomitant QT-prolonging drugs). Assess for signs of serotonin syndrome, especially if used with other serotonergic agents. Fetal monitoring not routinely required unless maternal complications arise. In pregnancy, monitor for severe nausea and vomiting to prevent dehydration and electrolyte imbalances. |
| Fertility Effects | No specific adverse effects on fertility have been reported in humans. Animal studies did not show impairment of fertility at doses up to 15 mg/kg/day. However, severe nausea and vomiting may indirectly affect reproductive health; treating such conditions may facilitate conception. |