What are the adverse effects of ondansetron?

Side Effects of Ondansetron

Ondansetron is generally well-tolerated with the most common adverse effects being headache (occurring in 17-28% of patients), constipation (7-11%), and transient asymptomatic elevations in liver transaminases (5-8%), while the most serious but rare adverse effect is QT interval prolongation leading to potentially fatal ventricular arrhythmias. 1, 2

Most Common Adverse Effects

Neurological

• Headache is the most frequently reported adverse effect, occurring in 17-28% of adult patients receiving ondansetron for chemotherapy-induced nausea and vomiting 2, 3, 4
• Lightheadedness, fatigue, and dizziness occur in fewer than 10% of patients 4

Gastrointestinal

• Constipation occurs in 7-11% of patients, particularly those receiving multi-day ondansetron therapy for chemotherapy 2, 5
• Diarrhea occurs in approximately 15% of patients receiving intravenous ondansetron, though this was less common than with metoclopramide (29%) 3
• In pediatric patients aged 1-24 months, diarrhea was seen more frequently (2%) compared with placebo (<1%) 2

Hepatic

• Transient asymptomatic elevations of serum aminotransferases (AST and ALT) exceeding twice the upper limit of normal occur in approximately 5-8% of chemotherapy patients with normal baseline values 1, 2
• These elevations are transient, not dose-related, and do not progress to symptomatic hepatic disease even on repeat exposure 2
• The incidence appears related to cisplatin dose rather than ondansetron dose 3

Serious but Rare Cardiovascular Adverse Effects

QT Interval Prolongation and Arrhythmias

• QT interval prolongation is the most serious adverse effect, which can lead to torsades de pointes and fatal ventricular tachycardia 6, 7, 8
• Special caution must be exercised in children with heart disease due to this QT prolongation risk 6, 9
• Doses greater than 8 mg should be avoided or used with extreme caution when co-administered with other QT-prolonging agents (citalopram, escitalopram, domperidone, certain antineoplastic drugs) 6, 7
• The combination of ondansetron >8mg with domperidone is contraindicated due to additive risk of torsades de pointes 7

Other Cardiovascular Effects

• Rare cases of angina (chest pain), electrocardiographic alterations, hypotension, and tachycardia have been reported 2
• Acute myocardial ischemia has been reported in adults 8

Less Common Adverse Effects

Dermatologic

• Rash occurs in approximately 1% of patients 2
• Fever and malaise have been reported 8

Neurological (Rare)

• Extrapyramidal reactions are rare but have been reported, though they are far less common than with metoclopramide (0% vs 5%) 1, 2, 3
• Rare cases of grand mal seizure have been reported 2

Metabolic

• Rare cases of hypokalemia have been reported 2

Pregnancy-Related Risks

• Ondansetron use during the first trimester has been associated with congenital cardiac defects and should only be administered as second-line therapy 9
• The American Gastroenterological Association recommends case-by-case use before 10 weeks of gestation due to potential risks of congenital cardiac defects 9

Critical Safety Monitoring

Patients Requiring Enhanced Surveillance

• Routine monitoring of serum potassium and magnesium levels is recommended for patients at risk for cardiac events (those with electrolyte disturbances, heart failure, or concurrent QT-prolonging medications) 6
• Baseline QTc interval should be evaluated, as ondansetron should be used cautiously if QTc is already prolonged 7

Drug Interactions to Avoid

• Active assessment for concomitant use with serotonergic agents (SSRIs, SNRIs, MAO inhibitors) is essential, as combinations heighten the likelihood of serious cardiac adverse events 6
• When ondansetron therapy is required, domperidone should be replaced with metomimazine to minimize QT-prolonging drug interactions 6, 7

Common Pitfalls to Avoid

• Do not use ondansetron in patients with suspected inflammatory diarrhea or diarrhea with fever, as it may mask serious bacterial gastroenteritis 6
• Do not assume ondansetron is safe in all pediatric patients—children under 4 years should receive oral rehydration solution as first-line therapy, and those with heart disease require special caution 6
• Do not overlook electrolyte abnormalities (hypokalemia from vomiting/diarrhea, corticosteroid use, or diuretics) that compound arrhythmia risk 7
• Do not combine ondansetron with other QT-prolonging medications without careful risk assessment and monitoring 6, 7