Zofran - Drug Monograph

Introduction

Zofran (ondansetron) is a selective serotonin 5-HT3 receptor antagonist developed by GlaxoSmithKline. It is primarily used for the prevention and treatment of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative recovery. First approved by the FDA in 1991, ondansetron has become a cornerstone therapy in antiemetic management across various clinical settings.

Mechanism of Action

Ondansetron exerts its antiemetic effects through selective antagonism of serotonin 5-HT3 receptors located both centrally in the chemoreceptor trigger zone (CTZ) of the area postrema and peripherally on vagal nerve terminals in the gastrointestinal tract. By blocking these receptors, ondansetron prevents serotonin-induced stimulation of the vomiting reflex pathway, thereby reducing nausea and vomiting episodes.

Indications

• Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
• Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy
• Prevention of postoperative nausea and vomiting (PONV)
• Prevention of nausea and vomiting associated with radiotherapy in patients receiving total body irradiation, single high-dose fraction, or daily fractions to the abdomen

Dosage and Administration

• Chemotherapy-induced nausea/vomiting: 8-24 mg orally 30 minutes before chemotherapy; or 0.15 mg/kg IV 30 minutes before chemotherapy
• Radiotherapy-induced nausea/vomiting: 8 mg orally three times daily
• Postoperative nausea/vomiting: 16 mg orally 1 hour before anesthesia; or 4 mg IV immediately before induction

• Chemotherapy-induced (4-18 years): 0.15 mg/kg IV before chemotherapy
• Postoperative (1 month-12 years): 0.1 mg/kg IV (maximum 4 mg)

• Hepatic impairment: Maximum daily dose 8 mg
• Renal impairment: No dosage adjustment required
• Elderly: No dosage adjustment required

Pharmacokinetics

• Absorption: Well absorbed orally (60% bioavailability); Tmax: 1.5-2 hours
• Distribution: Volume of distribution: 1.8-2.2 L/kg; Protein binding: 70-76%
• Metabolism: Extensive hepatic metabolism via multiple cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP3A4)
• Elimination: Half-life: 3-6 hours; Excretion: primarily urine (5% unchanged)

Contraindications

• Known hypersensitivity to ondansetron or any component of the formulation
• Concomitant use with apomorphine due to risk of profound hypotension and loss of consciousness
• Patients with congenital long QT syndrome

Warnings and Precautions

• QT Prolongation: Dose-dependent QT interval prolongation reported; use with caution in patients with cardiac conditions or electrolyte abnormalities
• Serotonin Syndrome: Risk increased with concomitant serotonergic drugs
• Hypersensitivity Reactions: Anaphylaxis, bronchospasm, and urticaria reported
• Masking of Progressive Ileus: Use with caution in abdominal surgery patients
• Phenylketonuria: Orally disintegrating tablets contain phenylalanine

Drug Interactions

• Apomorphine: Contraindicated combination
• Serotonergic Drugs: Increased risk of serotonin syndrome (SSRIs, SNRIs, tramadol)
• Drugs that Prolong QT Interval: Additive effects (antiarrhythmics, antipsychotics, antibiotics)
• CYP450 Inducers/Inhibitors: May alter ondansetron concentrations
• Tramadol: May reduce analgesic efficacy

Adverse Effects

• Headache (16-25%)
• Constipation (5-11%)
• Diarrhea (5-8%)
• Fatigue (5-13%)
• Dizziness (4-7%)

• QT prolongation and torsades de pointes
• Anaphylactic reactions
• Serotonin syndrome
• Extrapyramidal reactions
• Transient visual disturbances

Monitoring Parameters

• Efficacy of nausea/vomiting control
• ECG monitoring in patients at risk for QT prolongation
• Signs/symptoms of hypersensitivity reactions
• Electrolyte status (potassium, magnesium)
• Signs of serotonin syndrome
• Bowel function in postoperative patients

Patient Education

• Take medication as prescribed, usually 30 minutes before chemotherapy or 1 hour before surgery
• Report any chest pain, palpitations, or irregular heartbeat immediately
• Be aware of potential drug interactions with other medications
• Report severe constipation or abdominal pain
• Orally disintegrating tablets should be placed on tongue to dissolve
• Avoid alcohol during therapy
• Inform healthcare providers of all medications being taken
• Seek immediate medical attention for signs of allergic reaction

References

1. FDA Prescribing Information: Zofran (ondansetron) 2. Roila F, et al. Ann Oncol. 2016;27(suppl 5):v119-v133 3. ASCO Guidelines for Antiemetics in Oncology 4. Gan TJ, et al. Anesth Analg. 2014;118(1):85-113 5. Grunberg SM, et al. Cancer. 2011;117(4):842-852 6. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information 7. Micromedex Solutions, Greenwood Village, Colorado: IBM Watson Health