Usage
- Ondansetron is prescribed for the prevention and treatment of nausea and vomiting associated with:
- Highly and moderately emetogenic chemotherapy
- Radiotherapy
- Postoperative nausea and vomiting (PONV)
- Pharmacological classification: Antiemetic, 5-HT3 receptor antagonist.
- Mechanism of action: Ondansetron selectively blocks serotonin 5-HT3 receptors, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone (CTZ), thus inhibiting the vomiting reflex.
Alternate Names
- International Nonproprietary Name (INN): Ondansetron
- Brand names: Zofran, Zofran ODT, Zuplenz.
How It Works
- Pharmacodynamics: Ondansetron exerts its antiemetic effect by antagonizing serotonin 5-HT3 receptors in the gastrointestinal tract and the CTZ. This action blocks serotonin-induced nausea and vomiting.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Bioavailability is slightly reduced by food.
- Metabolism: Primarily hepatic, via CYP3A4, CYP2D6, and CYP1A2 enzymes.
- Elimination: Primarily renal (approximately 44-60% excreted unchanged in urine), with a small portion excreted in feces. The elimination half-life is approximately 3-6 hours in adults, longer in neonates and young children.
- Mode of Action: Competitive antagonism of 5-HT3 receptors on vagal afferent neurons in the gut and the CTZ.
- Receptor Binding/Enzyme Inhibition: Selective 5-HT3 receptor antagonist. It does not interact significantly with other receptor types, including dopamine, histamine, or muscarinic receptors.
- Elimination Pathways: Primarily renal excretion of unchanged drug and metabolites. Hepatic metabolism by CYP3A4, CYP2D6, and CYP1A2 contributes to clearance.
Dosage
Standard Dosage
Adults:
- Chemotherapy/Radiotherapy-induced Nausea/Vomiting:
- Moderately emetogenic chemotherapy: 8 mg orally 30 minutes before chemotherapy, followed by 8 mg every 12 hours for 1-2 days.
- Highly emetogenic chemotherapy: A single dose of up to 24 mg orally (with 12 mg dexamethasone) 1 to 2 hours before chemotherapy, or 0.15 mg/kg IV (max 16 mg/dose) 30 minutes before chemotherapy, then repeated 4 and 8 hours after the first dose. Continue oral dosing at 8 mg every 12 hours for 1-2 days following the intravenous dose.
- Postoperative Nausea/Vomiting:
- Prophylaxis: 16 mg orally 1 hour before anesthesia, or 4 mg IV immediately before or after surgery. Patients weighing >80 kg may require an additional 4 mg IV.
- Treatment: 4 mg IV for established PONV.
- Radiotherapy-induced Nausea/Vomiting: 8 mg orally 1-2 hours before treatment, followed by 8 mg every 8 hours (for total body irradiation and single high-dose fraction to the abdomen). Continue for 1 to 2 days after completion of abdominal therapy, but give the medication before radiotherapy with daily fractions to the abdomen.
Children (6 months and older):
- Chemotherapy-induced Nausea/Vomiting: 0.15 mg/kg IV (maximum 16 mg/dose), 30 minutes before chemotherapy, followed by doses at 4 and 8 hours after the first dose. Alternatively, the dose can be calculated based on body surface area. Oral dosing can begin 12 hours later at 4 mg twice daily for up to 5 days.
Special Cases:
- Elderly Patients: May require dose reduction, particularly for intravenous administration or in patients over 75 years old. Initial IV doses should be administered as a slow infusion. The maximum initial IV dose should not exceed 8 mg.
- Patients with Renal Impairment: No dosage adjustment necessary.
- Patients with Hepatic Dysfunction: Maximum daily dose 8 mg in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Caution in patients with cardiac conditions, electrolyte abnormalities, or those taking other QT-prolonging drugs.
Clinical Use Cases:
- Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use: IV administration is generally preferred for immediate control of nausea and vomiting. Standard dosing applies.
- Emergency Situations: IV administration for rapid control of nausea and vomiting.
Dosage Adjustments:
- Renal/Hepatic Dysfunction: As noted above.
- Metabolic disorders or genetic polymorphisms: No specific adjustments are routinely necessary. However, consider patient-specific factors and monitor for adverse effects.
Side Effects
Common Side Effects:
- Headache
- Constipation
- Diarrhea
- Fatigue/Drowsiness
Rare but Serious Side Effects:
- Hypersensitivity reactions (anaphylaxis, bronchospasm)
- QT prolongation, Torsade de Pointes
- Serotonin syndrome
Long-Term Effects:
No significant long-term effects reported with short-term use.
Adverse Drug Reactions (ADR):
- Anaphylaxis, bronchospasm
- QT prolongation, Torsade de Pointes
- Serotonin syndrome
Contraindications
- Hypersensitivity to ondansetron.
- Concomitant use with apomorphine.
Drug Interactions
- CYP450 Interactions: Ondansetron is metabolized by CYP3A4, CYP2D6, and CYP1A2. Inhibitors or inducers of these enzymes may alter ondansetron levels.
- Other clinically significant drug interactions:
- Apomorphine (contraindicated)
- QT prolonging drugs (additive effects)
- Serotonergic drugs (risk of serotonin syndrome)
- Commonly prescribed medications: Interactions may occur with certain antidepressants, antipsychotics, and antibiotics.
- OTC drugs and supplements: No well-documented significant interactions.
- Food and lifestyle factors: Food may slightly decrease bioavailability. No significant interaction with alcohol or smoking.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Previously Category B, now no official US FDA category exists. While large studies have not shown increased risk of major birth defects, some studies have shown a small increased risk of certain orofacial clefts. Consult with a specialist for detailed risk assessment.
- Fetal risks: Possible but unconfirmed increased risk of orofacial clefts.
- Breastfeeding: Ondansetron is present in breast milk in small amounts. Generally considered safe to use during breastfeeding, with monitoring for infant side effects like gastrointestinal discomfort. Neonatal effects are considered minimal.
Drug Profile Summary
- Mechanism of Action: 5-HT3 receptor antagonist, blocking serotonin-induced nausea and vomiting.
- Side Effects: Headache, constipation, diarrhea, fatigue; rarely QT prolongation, serotonin syndrome, hypersensitivity.
- Contraindications: Hypersensitivity to ondansetron, concomitant apomorphine.
- Drug Interactions: QT prolonging drugs, serotonergic drugs, CYP3A4 inhibitors/inducers.
- Pregnancy & Breastfeeding: Consult specialist regarding pregnancy. Generally safe during breastfeeding, monitor infant.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: ECG (in patients at risk for QT prolongation), signs of serotonin syndrome or hypersensitivity.
Popular Combinations
- Dexamethasone with ondansetron for highly emetogenic chemotherapy to enhance antiemetic efficacy.
Precautions
- General Precautions: Assess for allergies, cardiac conditions, electrolyte abnormalities, hepatic/renal function.
- Specific Populations: Monitor pregnancy closely. Generally safe during breastfeeding but monitor infant. Age-appropriate dosing for children and elderly.
- Lifestyle Considerations: May impair alertness, caution with driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ondansetron?
A: See the detailed dosage guidelines above for adults, children, and special populations.
Q2: How should Ondansetron be administered?
A: Available as oral tablets, oral disintegrating tablets, oral solution, oral soluble film, and injectable solution for IV or IM administration.
Q3: What are the most common side effects of Ondansetron?
A: Headache, constipation, and diarrhea are the most frequently reported side effects.
Q4: Are there any serious side effects to watch for with Ondansetron?
A: Yes, though rare. Monitor for hypersensitivity reactions, QT prolongation (especially in at-risk patients), and serotonin syndrome.
Q5: Can Ondansetron be used in patients with liver disease?
A: Yes, but the maximum daily dose should be reduced to 8 mg in moderate to severe hepatic impairment.
Q6: Can Ondansetron be used in pregnant women?
A: Consult with a specialist for assessment of the risks and benefits. While generally considered safe, some studies have shown a small increased risk of certain orofacial clefts.
Q7: Can Ondansetron be used during breastfeeding?
A: Generally considered safe. Small amounts are present in breast milk. Monitor the infant for any potential adverse effects, like gastrointestinal discomfort.
Q8: What other medications should be avoided while taking Ondansetron?
A: Avoid apomorphine. Caution should be used when co-administering ondansetron with other QT-prolonging drugs or serotonergic medications.
A: Ondansetron is metabolized by CYP3A4. Concomitant use of CYP3A4 inhibitors may increase ondansetron levels, while inducers may decrease levels. Dosage adjustments may be needed.
Q10: Can Ondansetron be used in the emergency setting?
A: Yes, IV administration is frequently used in emergency settings to rapidly control nausea and vomiting.
