Ondansetron

Uses

Ondansetron, a selective serotonin (5-HT3) receptor antagonist, is widely used for the prevention and treatment of nausea and vomiting. Its primary indications include:

Primary Indications

1. Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV):

   • Effective in both acute and delayed phases of CINV when used alone or in combination with corticosteroids (e.g., dexamethasone).

2. Prevention of Postoperative Nausea and Vomiting (PONV):

   • Used preoperatively or postoperatively to reduce the incidence of nausea and vomiting in patients undergoing surgical procedures.

3. Radiotherapy-Induced Nausea and Vomiting:

   • Prevents nausea and vomiting associated with total body irradiation or high-dose radiotherapy to the abdomen or pelvis.

4. Treatment of Gastroenteritis-Induced Nausea and Vomiting:

   • Commonly used off-label to alleviate nausea and vomiting caused by acute viral or bacterial gastroenteritis, particularly in pediatric and emergency care settings.

5. Hyperemesis Gravidarum (off-label use):

   • Sometimes used in severe cases of pregnancy-induced nausea and vomiting when other treatments are ineffective.

Dosage and Administration

Adults:

1. CINV:

   • Oral: 8 mg 30 minutes before chemotherapy, followed by 8 mg every 12 hours for 1–2 days after chemotherapy.
   • IV: 8–16 mg as a single dose before chemotherapy.

2. PONV:

   • IV: 4 mg as a single dose at induction of anesthesia.
   • Oral: 16 mg taken 1 hour before anesthesia.

3. Radiotherapy-Induced Nausea and Vomiting:

   • Oral: 8 mg 1–2 hours before radiotherapy, followed by 8 mg every 8 hours.

4. Gastroenteritis:

   • Oral or IV: 4–8 mg as needed, depending on severity.

Pediatrics:

1. CINV/PONV:

   • IV: 0.1–0.15 mg/kg (maximum single dose: 4 mg), administered prior to chemotherapy or surgery.
   • Oral: 4 mg for children aged 4–11 years; 8 mg for those aged ≥12 years.

2. Gastroenteritis:

   • Oral: 0.15 mg/kg (maximum single dose: 4 mg).

Presentation

1. Oral Tablets: 4 mg, 8 mg.
2. Oral Disintegrating Tablets (ODT): 4 mg, 8 mg.
3. Oral Solution: 4 mg/5 mL.
4. Injectable Solution: 2 mg/mL, 4 mg/2 mL ampoules.

Mechanism of Action

Ondansetron selectively inhibits serotonin 5-HT3 receptors located:

• In the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS).
• Peripherally in the vagal nerve terminals.

By blocking serotonin’s action, ondansetron prevents the signaling cascade that leads to nausea and vomiting.

Precautions and Safety

1. QT Prolongation:

   • Ondansetron can prolong the QT interval, potentially leading to torsades de pointes.
   • Caution is advised in patients with:
     • Congenital long QT syndrome.
     • Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia).
     • Use of other QT-prolonging drugs (e.g., amiodarone).

2. Hepatic Impairment:

   • Dose adjustment is necessary in severe hepatic impairment (maximum daily dose: 8 mg).

3. Serotonin Syndrome:

   • Rare but serious, especially when combined with other serotonergic drugs (e.g., SSRIs, SNRIs, tramadol). Symptoms include agitation, confusion, tachycardia, hyperreflexia, and diarrhea.

4. Allergic Reactions:

   • Hypersensitivity reactions, including anaphylaxis, are rare but documented.

Side Effects

Common:

• Headache.
• Constipation.
• Dizziness.
• Fatigue or malaise.

Less Common but Serious:

• QT interval prolongation and arrhythmias.
• Serotonin syndrome (when used with serotonergic agents).
• Hypersensitivity reactions (e.g., rash, bronchospasm).

Recent Updates and Guidelines

1. American Society of Clinical Oncology (ASCO) 2023 Guidelines:

   • Recommends the use of ondansetron in combination with neurokinin-1 receptor antagonists (e.g., aprepitant) and corticosteroids for highly emetogenic chemotherapy.

2. National Institute for Health and Care Excellence (NICE) 2022:

   • Supports ondansetron’s off-label use in pediatric gastroenteritis to reduce hospital admissions and improve oral rehydration therapy success rates.

3. FDA Update on QT Prolongation Risk (2020):

   • Reinforces the need for ECG monitoring in high-risk patients receiving ondansetron intravenously, especially at doses exceeding 16 mg.

References

1. National Comprehensive Cancer Network (NCCN) Guidelines: Antiemesis (2023).
2. American Society of Clinical Oncology (ASCO): Antiemetic Guidelines (2023).
3. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics (13th Edition).
4. NICE Guidelines: Management of Gastroenteritis in Children (2022).
5. FDA Drug Safety Communication: Ondansetron and QT Prolongation (2020).