What are the side effects of Zofran (ondansetron)?

Side Effects of Zofran (Ondansetron)

Ondansetron (Zofran) commonly causes headache, constipation, and diarrhea as side effects, but its most serious adverse effects include QT interval prolongation, which can lead to potentially fatal cardiac arrhythmias. 1

Common Side Effects

• Gastrointestinal effects: Constipation, diarrhea, and abdominal pain are frequently reported side effects 1, 2
• Headache: Occurs in approximately 11-24% of patients, making it one of the most common adverse reactions 1, 3
• Malaise/fatigue: Reported in about 13% of patients taking ondansetron 1

Serious Side Effects

Cardiovascular Effects

• QT interval prolongation: Can lead to Torsade de Pointes, a potentially fatal arrhythmia 1, 4
• Myocardial ischemia: Has been reported, particularly during intravenous administration 1
• ECG changes: Require monitoring in patients with electrolyte abnormalities, congestive heart failure, or bradyarrhythmias 1

Neurological Effects

• Serotonin syndrome: Risk increases when combined with other serotonergic drugs (SSRIs, SNRIs, tramadol, etc.) 1
• Extrapyramidal reactions: Reported in less than 1% of patients 1
• Seizures: Rare but reported 1

Other Serious Concerns

• Hypersensitivity reactions: Including anaphylaxis and bronchospasm 1
• Masking of progressive ileus and gastric distention: Particularly concerning in post-surgical patients 1
• Hepatic effects: Transient elevations in liver enzymes (AST/ALT) in 1-2% of patients 1

Special Populations and Considerations

Cardiac Risk Factors

• Contraindicated in congenital long QT syndrome 1
• Requires ECG monitoring in patients with:
  • Electrolyte abnormalities (hypokalemia, hypomagnesemia)
  • Congestive heart failure
  • Bradyarrhythmias
  • Concurrent use of other QT-prolonging medications 1, 4

Drug Interactions

• Increased risk of serotonin syndrome when used with:
  • SSRIs and SNRIs
  • Monoamine oxidase inhibitors
  • Mirtazapine
  • Fentanyl
  • Lithium
  • Tramadol 1

Overdose Concerns

• Symptoms of overdose include:
  • Sudden temporary blindness
  • Severe constipation
  • Hypotension
  • Vasovagal episodes
  • Serotonin syndrome (particularly in children) 1

Specific Uses and Considerations

In Gastrointestinal Disorders

• Effective for nausea and vomiting in irritable bowel syndrome with diarrhea, but constipation is a common side effect 5
• May mask symptoms of bowel obstruction in post-surgical patients 1

In Pregnancy

• Used as a second-line therapy for hyperemesis gravidarum
• Some studies have reported cases of congenital heart defects when used in the first trimester 5

In Children

• Pediatric overdose can result in serotonin syndrome with symptoms including somnolence, agitation, tachycardia, and seizures 1
• Used in children over 4 years old with acute gastroenteritis to facilitate oral rehydration, though it may increase stool volume 5

Pharmacokinetic Considerations

• Rapidly absorbed after oral administration with bioavailability of about 60% 6
• Widely distributed with moderate protein binding (70-76%) 6
• Primarily eliminated through hepatic metabolism (95%) 6
• Half-life averages approximately 3.8 hours 6

Monitoring Recommendations

• ECG monitoring in patients with cardiac risk factors 1
• Watch for signs of serotonin syndrome when combined with other serotonergic medications 1
• Monitor for decreased bowel activity in patients at risk for gastrointestinal obstruction 1
• Observe for signs of myocardial ischemia after administration 1