Zofran

Zofran (ondansetron) is a highly selective 5-HT3 receptor antagonist indicated for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, radiotherapy, and postoperative recovery. It is a cornerstone of modern antiemetic therapy, offering targeted action with a well-established efficacy and safety profile. Its mechanism provides a significant advancement in supportive care, improving patient quality of life and treatment adherence.

Features

• Active Ingredient: Ondansetron hydrochloride.
• Available Formulations: Oral tablets (4mg, 8mg), orally disintegrating tablets (4mg, 8mg), oral solution (4mg/5mL), and injectable solution (2mg/mL).
• Mechanism of Action: Selective antagonism of serotonin 5-HT3 receptors in the central and peripheral nervous systems.
• Onset of Action: Oral: ~1-2 hours; IV: within minutes.
• Duration of Effect: Up to 24 hours following a single dose.
• Bioavailability: Approximately 60% for oral formulations.

Benefits

• Provides rapid and effective control of acute nausea and vomiting.
• Reduces the need for rescue antiemetic medication.
• Supports completion of chemotherapy and radiotherapy regimens.
• Minimizes postoperative complications related to emesis.
• Available in multiple formulations for flexible administration.
• Generally well-tolerated with a favorable side effect profile.

Common use

Zofran is primarily prescribed for the prevention and treatment of nausea and vomiting in three key clinical scenarios. First, it is a first-line agent for preventing chemotherapy-induced nausea and vomiting (CINV), particularly with moderately to highly emetogenic regimens, often as part of a combination antiemetic protocol. Second, it is used for the prevention of nausea and vomiting associated with radiotherapy. Third, it is indicated for the prevention and treatment of postoperative nausea and vomiting (PONV) in patients who have undergone surgical procedures. Off-label uses may include management of nausea and vomiting in hyperemesis gravidarum (under specialist supervision) and gastroenteritis, though evidence and guidelines for these uses vary.

Dosage and direction

Dosage is highly indication-specific and must be individualized.

For Chemotherapy-Induced Nausea and Vomiting: Adults:

• IV: 0.15 mg/kg administered 30 minutes before chemotherapy, then repeated 4 and 8 hours after the first dose. Alternatively, a single 32 mg dose may be used.
• Oral: 24 mg given as three 8 mg tablets 30 minutes before the start of single-day highly emetogenic chemotherapy. For moderately emetogenic chemotherapy: 8 mg orally twice daily. The first dose should be administered 30 minutes before chemotherapy, with subsequent doses 8 hours after the first dose, then every 12 hours for 1 to 2 days after chemotherapy completion.

Pediatric Patients (4-18 years): Dosing is based on body surface area or weight. Consult specific pediatric dosing protocols.

For Radiotherapy-Induced Nausea and Vomiting: Adults: 8 mg orally taken 1 to 2 hours before radiotherapy, and every 8 hours after the first dose for the duration of radiotherapy sessions.

For Postoperative Nausea and Vomiting (PONV): Adults:

• Prevention: 16 mg orally or 4 mg IV undiluted administered over 2-5 minutes immediately before induction of anesthesia.
• Treatment: 4 mg IV administered over 2-5 minutes for patients who experience nausea/vomiting shortly after surgery.

Oral Administration: Tablets can be taken with or without food. Orally disintegrating tablets should be placed on the tongue and will dissolve rapidly; they may be swallowed with saliva. No water is needed.

Precautions

• Cardiac Effects: Use with caution in patients with underlying cardiac conditions (e.g., congenital long QT syndrome, congestive heart failure, bradyarrhythmias) or those taking other medications that prolong the QT interval. Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia) should be corrected prior to and during administration.
• Serotonin Syndrome: There have been reports of serotonin syndrome with the use of 5-HT3 receptor antagonists, especially when used concomitantly with other serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, fentanyl, lithium, tramadol, and drugs that impair metabolism of serotonin). Monitor for symptoms such as mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms.
• Gastrointestinal Motility: Ondansetron does not stimulate gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. Use in patients with abdominal surgery or chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distention.
• Phenylketonurics: Orally disintegrating tablets contain aspartame, which is a source of phenylalanine (approximately 1.7 mg and 3.4 mg per 4 mg and 8 mg tablet, respectively).
• Hepatic Impairment: In patients with severe hepatic impairment, total daily dose should not exceed 8 mg due to decreased clearance.

Contraindications

Zofran is contraindicated in patients with:

• Known hypersensitivity to ondansetron or any component of the formulation.
• Concomitant use of apomorphine due to the risk of profound hypotension and loss of consciousness.
• Patients with a history of phenylketonuria should avoid the orally disintegrating tablet formulation.

Possible side effect

The most common side effects are generally mild and transient.

• Very Common (≥1/10): Headache, constipation.
• Common (≥1/100 to <1/10): Sensation of warmth or flushing, dizziness, drowsiness (somnolence), fatigue, transient asymptomatic increases in liver transaminases, hiccups, injection site reactions (for IV formulation).
• Uncommon (≥1/1,000 to <1/100): Chest pain, palpitations, bradycardia, tachycardia, syncope, hypotension, blurred vision, involuntary motor movements, seizures, hypokalemia.
• Rare (<1/1,000): Anaphylaxis, angioedema, bronchospasm, shock, arrhythmias (including QT interval prolongation and Torsade de Pointes), extrapyramidal reactions, transient blindness.

Drug interaction

• Drugs that Prolong QT Interval: Concomitant use with other drugs known to prolong the QT interval (e.g., certain antiarrhythmics [amiodarone, sotalol], antipsychotics [haloperidol, pimozide], antibiotics [erythromycin, moxifloxacin], antidepressants) may result in additive effects and increased risk of malignant arrhythmias. Avoid concomitant use or monitor ECG closely.
• Serotonergic Drugs: Concomitant use with other serotonergic drugs (SSRIs, SNRIs, MAOIs, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort) may increase the risk of serotonin syndrome.
• Apomorphine: Contraindicated. Ondansetron may cause profound hypotension and loss of consciousness.
• Phenytoin, Carbamazepine, Rifampin: These CYP3A4 inducers may increase ondansetron clearance and decrease plasma concentrations, potentially reducing efficacy.
• Tramadol: Ondansetron may inhibit the analgesic effect of tramadol.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped, and the regular dosing schedule resumed. Do not double the dose to make up for a missed one. For scheduled chemotherapy or surgical prophylaxis, the timing relative to the procedure is critical; contact the prescribing physician for guidance if a pre-procedural dose is missed.

Overdose

Symptoms of overdose may be an exaggeration of known adverse effects. Reported effects include sudden transient blindness, severe constipation, hypotension, and syncope. In specific cases, especially with IV administration, QT prolongation and ventricular arrhythmias have been observed. There is no specific antidote for ondansetron overdose. Management consists of discontinuation of the drug and supportive and symptomatic therapy, including continuous ECG monitoring for at least 24 hours. Hemodialysis is not likely to be effective in enhancing elimination.

Storage

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
• Protect from light.
• Keep the blister packages for orally disintegrating tablets dry.
• Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided may not cover all possible uses, directions, precautions, drug interactions, or adverse effects.

Reviews

Zofran is consistently highly rated in clinical practice and by patients for its efficacy in controlling debilitating nausea and vomiting. It is considered a gold-standard antiemetic in oncology and anesthesiology. Clinical studies and meta-analyses repeatedly demonstrate its superiority over older antiemetics like metoclopramide in the prevention of CINV and PONV. Patient testimonials frequently highlight its role in enabling them to tolerate and complete difficult cancer treatments. The main critiques in the literature pertain to its cost compared to older generic agents and the potential for QT prolongation at high IV doses, leading to more cautious use in certain patient populations. Overall, its benefit-risk profile remains overwhelmingly positive for its approved indications.