What are the contraindications for Zofran (ondansetron)?

Contraindications for Zofran (Ondansetron)

Zofran (ondansetron) is contraindicated in patients with known hypersensitivity to ondansetron or any components of the formulation, and in patients receiving concomitant apomorphine due to risk of profound hypotension and loss of consciousness. 1

Absolute Contraindications

1. Hypersensitivity reactions:

   • Known hypersensitivity to ondansetron or any components of the formulation 1
   • Previous anaphylactic or anaphylactoid reactions 2
   • Reactions can include anaphylaxis and bronchospasm

2. Concomitant apomorphine use:

   • Combined use can cause profound hypotension and loss of consciousness 1

Relative Contraindications/Precautions

1. Cardiac conditions:

   • Congenital long QT syndrome 1
   • Electrolyte abnormalities (hypokalemia, hypomagnesemia) 1
   • Congestive heart failure 1
   • Bradyarrhythmias 1
   • Use with other medications that prolong QT interval 1
   • History of myocardial ischemia (risk of coronary artery spasm) 1

2. Risk of serotonin syndrome when used with:

   • Selective serotonin reuptake inhibitors (SSRIs) 1
   • Serotonin and norepinephrine reuptake inhibitors (SNRIs) 1
   • Monoamine oxidase inhibitors (MAOIs) 1
   • Other serotonergic drugs (mirtazapine, fentanyl, lithium, tramadol) 1
   • Intravenous methylene blue 1

3. Hepatic impairment:

   • Severe hepatic impairment (Child-Pugh score ≥10) requires dose adjustment (maximum daily dose of 8 mg) 1

Special Populations and Considerations

1. Pregnancy:

   • Use caution during pregnancy as safety data is limited
   • Risk-benefit assessment should be performed

2. Elderly patients:

   • While aging is associated with decreased clearance and increased bioavailability, specific dosage adjustments are generally not required 3

3. Patients with cancer:

   • May have slightly enhanced bioavailability 3

Monitoring Recommendations

1. ECG monitoring recommended in patients with:

   • Electrolyte abnormalities 1
   • Congestive heart failure 1
   • Bradyarrhythmias 1
   • Concurrent use of QT-prolonging medications 1

2. Monitor for signs of serotonin syndrome:

   • Mental status changes (agitation, hallucinations, delirium, coma) 1
   • Autonomic instability (tachycardia, labile blood pressure, hyperthermia) 1
   • Neuromuscular symptoms (tremor, rigidity, myoclonus) 1
   • Seizures 1
   • Gastrointestinal symptoms 1

Clinical Pearls

• High-dose ondansetron (32 mg IV or equivalent) has greater risk of QT prolongation than lower doses 4
• Ondansetron should be administered at least 30 minutes before chemotherapy for optimal effect 3
• The FDA has issued specific warnings regarding QT interval prolongation with ondansetron, particularly at higher doses 4
• While there have been concerns about potential kidney injury, recent evidence suggests ondansetron is not associated with increased risk of acute kidney injury in critically ill patients 5

By understanding these contraindications and taking appropriate precautions, clinicians can safely prescribe ondansetron for its approved indications while minimizing potential adverse effects.