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

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).
Prevention of Postoperative Nausea and Vomiting (PONV):
- Used preoperatively or postoperatively to reduce the incidence of nausea and vomiting in patients undergoing surgical procedures.
Radiotherapy-Induced Nausea and Vomiting:
- Prevents nausea and vomiting associated with total body irradiation or high-dose radiotherapy to the abdomen or pelvis.
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.
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:

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.
PONV:
- IV: 4 mg as a single dose at induction of anesthesia.
- Oral: 16 mg taken 1 hour before anesthesia.
Radiotherapy-Induced Nausea and Vomiting:
- Oral: 8 mg 1–2 hours before radiotherapy, followed by 8 mg every 8 hours.
Gastroenteritis:
- Oral or IV: 4–8 mg as needed, depending on severity.

Pediatrics:

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

Presentation

Oral Tablets: 4 mg, 8 mg.
Oral Disintegrating Tablets (ODT): 4 mg, 8 mg.
Oral Solution: 4 mg/5 mL.
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

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

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.
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.
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.