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. |
| Molecular Weight | 293.36 |
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 | Use only if clearly needed; limited data suggest no major teratogenic risk, but avoid in first trimester due to theoretical risk. |
| 2nd trimester | Use if benefit outweighs risk; no known fetal harm. |
| 3rd trimester | Use if benefit outweighs risk; monitor for potential neonatal effects. |
Clinical note
Comprehensive clinical and safety monograph for ZOFRAN (ZOFRAN).
| Placental transfer | Ondansetron crosses the placenta; fetal plasma concentrations similar to maternal. |
| Breastfeeding | Ondansetron is excreted into breast milk in low amounts; relative infant dose <5%. Use with caution, especially in preterm infants or those with QT prolongation risk. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to ondansetron or any componentConcomitant use of apomorphineCongenital long QT syndrome
| 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 |
| Food/Dietary | No significant food interactions. Grapefruit juice does not affect ondansetron metabolism. Avoid excessive alcohol consumption as it may worsen nausea and increase CNS depression. |
Loading safety data…
| L2 (Limited data - probably compatible) |
| 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. |
| 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. |
| Clinical Pearls | ONDANSETRON (ZOFRAN) IS A 5-HT3 RECEPTOR ANTAGONIST WITH HIGH POTENCY FOR PREVENTING CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV) AND POSTOPERATIVE NAUSEA AND VOMITING (PONV). IT IS LESS EFFECTIVE FOR MOTION SICKNESS. ORAL DISINTEGRATING TABLETS (ODT) ARE AVAILABLE FOR PATIENTS WITH SWALLOWING DIFFICULTY. QT PROLONGATION RISK EXISTS, ESPECIALLY WITH HIGH DOSES, HYPOKALEMIA, HYPOMAGNESEMIA, OR CONCOMITANT QT-PROLONGING DRUGS. IV INJECTION SHOULD BE OVER 2-5 MINUTES TO REDUCE RISK OF HYPOTENSION AND DYSTONIC REACTIONS. AVOID USE IN PATIENTS WITH CONGENITAL LONG QT SYNDROME. MAXIMUM SINGLE IV DOSE IS 16 MG; ORAL DOSES TYPICALLY 8 MG BID OR TID. |
| Patient Advice | Take exactly as prescribed; do not exceed the recommended dose. · Oral tablets, ODT, and oral solution are available; ODT dissolves on tongue without water. · May cause headache, constipation, or drowsiness. · Seek immediate medical attention if you experience irregular heartbeat, dizziness, or fainting. · Inform your doctor of all medications you take, especially those affecting heart rhythm. · Avoid driving or operating heavy machinery if drowsiness occurs. · Do not use for prevention of motion sickness; it is not effective. · If you miss a dose, take it as soon as remembered unless near time for next dose; do not double dose. |