ZOFRAN PRESERVATIVE FREE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOFRAN PRESERVATIVE FREE (ZOFRAN PRESERVATIVE FREE).

How it works

Selective 5-HT3 receptor antagonist; blocks serotonin binding at 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) and gastrointestinal tract, inhibiting emetic reflex.

What the body does with it

Metabolism	Hepatic metabolism via CYP1A2, CYP2D6, and CYP3A4; minor contribution from flavin-containing monooxygenase (FMO).
Excretion	Approximately 5% of ondansetron is excreted unchanged in urine; the remainder is extensively metabolized, with metabolites excreted in urine (46-60%) and feces (22-29%).
Half-life	Terminal elimination half-life is approximately 3-6 hours in adults, but may be prolonged to 15-20 hours in severe hepatic impairment (Child-Pugh class C).
Protein binding	70-76% bound to plasma proteins.
Volume of Distribution	Vd approximately 1.9-2.5 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 60% due to first-pass metabolism; bioavailability is not applicable for IV and IM routes (100%).
Onset of Action	Intravenous: within 1-2 minutes; oral: within 30-60 minutes; intramuscular: within 10-20 minutes; orally disintegrating tablet: within 30-60 minutes.
Duration of Action	Duration of antiemetic effect is 4-8 hours after IV administration; up to 6-12 hours after oral administration; may be prolonged with hepatic impairment.

Classification & Brands

Dosing & administration

4-8 mg intravenously or intramuscularly as a single dose for prevention of chemotherapy-induced nausea and vomiting; 8 mg orally 30 minutes before chemotherapy, repeated every 8-12 hours as needed.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for GFR >30 mL/min; for GFR ≤30 mL/min, dosing interval should be extended to every 24 hours.
Liver impairment	Severe hepatic impairment (Child-Pugh C): maximum daily dose of 8 mg; moderate impairment (Child-Pugh B): no dose adjustment recommended; mild impairment (Child-Pugh A): no adjustment.
Pediatric use	For chemotherapy-induced nausea and vomiting: intravenous dose of 0.15 mg/kg per dose (maximum 8 mg) given 30 minutes before chemotherapy, repeated every 4 hours; orally: 4 mg for children ≤30 kg, 8 mg for children >30 kg, given 30 minutes before chemotherapy.
Geriatric use	No specific dose adjustment required; however, due to potential reduced renal function, consider monitoring and possible interval extension as per renal adjustment guidelines.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZOFRAN PRESERVATIVE FREE (ZOFRAN PRESERVATIVE FREE).

Breastfeeding	Ondansetron is excreted into human breast milk in low amounts. The milk-to-plasma ratio (M/P) is approximately 1.2. Relative infant dose is <0.5% of maternal weight-adjusted dose, considered compatible with breastfeeding. No adverse effects in breastfed infants reported.
Teratogenic Risk	First trimester: Limited human data; no increased risk of major malformations observed in epidemiological studies. Second and third trimesters: No evidence of fetal harm; ondansetron crosses placenta but no teratogenic effects reported. However, retrospective studies suggest a possible small increased risk of cleft palate with first-trimester use, not confirmed by large cohort studies.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to ondansetron or any component; concomitant use of apomorphine (reports of profound hypotension and loss of consciousness); congenital long QT syndrome.

Clinical Precautions

Precautions

QTc interval prolongation (dose-dependent); serotonin syndrome (especially with concomitant serotonergic drugs); masked ileus or gastric distension; hypersensitivity reactions including anaphylaxis; electrolyte abnormalities (hypokalemia, hypomagnesemia) increase arrhythmia risk.

Clinical Tips & Counseling

Drug interactions

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ZOFRAN PRESERVATIVE FREE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZOFRAN PRESERVATIVE FREE (ZOFRAN PRESERVATIVE FREE).

How it works

Selective 5-HT3 receptor antagonist; blocks serotonin binding at 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) and gastrointestinal tract, inhibiting emetic reflex.

What the body does with it

Metabolism	Hepatic metabolism via CYP1A2, CYP2D6, and CYP3A4; minor contribution from flavin-containing monooxygenase (FMO).
Excretion	Approximately 5% of ondansetron is excreted unchanged in urine; the remainder is extensively metabolized, with metabolites excreted in urine (46-60%) and feces (22-29%).
Half-life	Terminal elimination half-life is approximately 3-6 hours in adults, but may be prolonged to 15-20 hours in severe hepatic impairment (Child-Pugh class C).
Protein binding	70-76% bound to plasma proteins.
Volume of Distribution	Vd approximately 1.9-2.5 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is approximately 60% due to first-pass metabolism; bioavailability is not applicable for IV and IM routes (100%).
Onset of Action	Intravenous: within 1-2 minutes; oral: within 30-60 minutes; intramuscular: within 10-20 minutes; orally disintegrating tablet: within 30-60 minutes.
Duration of Action	Duration of antiemetic effect is 4-8 hours after IV administration; up to 6-12 hours after oral administration; may be prolonged with hepatic impairment.

Classification & Brands

Dosing & administration

4-8 mg intravenously or intramuscularly as a single dose for prevention of chemotherapy-induced nausea and vomiting; 8 mg orally 30 minutes before chemotherapy, repeated every 8-12 hours as needed.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for GFR >30 mL/min; for GFR ≤30 mL/min, dosing interval should be extended to every 24 hours.
Liver impairment	Severe hepatic impairment (Child-Pugh C): maximum daily dose of 8 mg; moderate impairment (Child-Pugh B): no dose adjustment recommended; mild impairment (Child-Pugh A): no adjustment.
Pediatric use	For chemotherapy-induced nausea and vomiting: intravenous dose of 0.15 mg/kg per dose (maximum 8 mg) given 30 minutes before chemotherapy, repeated every 4 hours; orally: 4 mg for children ≤30 kg, 8 mg for children >30 kg, given 30 minutes before chemotherapy.
Geriatric use	No specific dose adjustment required; however, due to potential reduced renal function, consider monitoring and possible interval extension as per renal adjustment guidelines.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ZOFRAN PRESERVATIVE FREE (ZOFRAN PRESERVATIVE FREE).

Breastfeeding	Ondansetron is excreted into human breast milk in low amounts. The milk-to-plasma ratio (M/P) is approximately 1.2. Relative infant dose is <0.5% of maternal weight-adjusted dose, considered compatible with breastfeeding. No adverse effects in breastfed infants reported.
Teratogenic Risk	First trimester: Limited human data; no increased risk of major malformations observed in epidemiological studies. Second and third trimesters: No evidence of fetal harm; ondansetron crosses placenta but no teratogenic effects reported. However, retrospective studies suggest a possible small increased risk of cleft palate with first-trimester use, not confirmed by large cohort studies.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Known hypersensitivity to ondansetron or any component; concomitant use of apomorphine (reports of profound hypotension and loss of consciousness); congenital long QT syndrome.