What are the potential side effects of ondansetron (Zofran), particularly in patients with a history of gastrointestinal disorders or those undergoing chemotherapy, radiation therapy, or surgery?

Ondansetron Side Effects

Ondansetron is generally well-tolerated with the most common side effects being headache (11-24%) and constipation (9%), but serious cardiac risks including QT prolongation and rare cases of Torsade de Pointes require caution in high-risk patients. 1

Common Side Effects

Most Frequent Adverse Events

• Headache occurs in 11-24% of patients, making it the most common side effect across all indications 1, 2
• Constipation affects approximately 9% of patients receiving ondansetron for chemotherapy-induced nausea, which can be particularly problematic as it may worsen nausea if not addressed 1, 3
• Diarrhea occurs in 4-6% of patients, and paradoxically, ondansetron may increase stool volume in some patients with acute gastroenteritis 1, 4
• Malaise/fatigue is reported in 13% of patients receiving ondansetron for moderately emetogenic chemotherapy 1

Less Common but Notable Effects

• Dizziness, musculoskeletal pain, drowsiness, and shivers are minor side effects reported in perioperative use 5
• Transient elevation of liver enzymes (AST/ALT exceeding twice the upper limit of normal) occurs in 1-2% of patients, though symptomatic hepatic disease is rare 1

Serious Cardiac Risks

QT Prolongation and Arrhythmias

• QT interval prolongation is a well-documented risk, with postmarketing cases of Torsade de Pointes reported in patients using ondansetron 1
• Avoid ondansetron entirely in patients with congenital long QT syndrome 1
• ECG monitoring is recommended in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, bradyarrhythmias, or those taking other QT-prolonging medications 1, 4
• The FDA specifically warned about the 32 mg IV dose due to cardiac concerns, though lower doses may also prolong QT intervals 6

Myocardial Ischemia

• Coronary artery spasm appears to be the most common underlying cause of myocardial ischemia associated with ondansetron 1
• Symptoms may appear immediately after administration but typically resolve with prompt treatment 1
• Monitor patients for chest pain or tightness after oral administration, particularly in those with cardiovascular risk factors 1

Serious Non-Cardiac Risks

Hypersensitivity Reactions

• Anaphylaxis and bronchospasm have been reported, particularly in patients with hypersensitivity to other 5-HT3 receptor antagonists 1
• Discontinue ondansetron immediately if hypersensitivity reactions occur and treat per standard of care 1

Serotonin Syndrome

• Risk is highest with concomitant serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, mirtazapine, fentanyl, lithium, tramadol, and IV methylene blue 1
• Symptoms include mental status changes (agitation, hallucinations, delirium), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus), and GI symptoms 1
• Most cases occur in post-anesthesia care units or infusion centers, with some fatal cases reported 1
• Discontinue ondansetron and initiate supportive treatment if serotonin syndrome develops 1

Special Considerations in Gastrointestinal Disorders

Masking of Bowel Obstruction

• Ondansetron may mask progressive ileus and gastric distension in patients following abdominal surgery or those with chemotherapy-induced nausea 1
• Monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction 1
• Ondansetron does not stimulate gastric or intestinal peristalsis and should not replace nasogastric suction when indicated 1

Constipation Risk

• Regular use can cause constipation, which is particularly problematic in patients already at risk (e.g., those receiving opioids) 4
• Consider prophylactic stool softeners in high-risk patients 7

Comparative Safety Profile

Advantages Over Older Antiemetics

• Lower incidence of sedation compared to conventional antiemetics like droperidol and metoclopramide 5
• Isolated case reports only of extrapyramidal reactions (less than 1% of patients), unlike dopamine antagonists 1, 8
• Does not worsen Parkinson's disease symptoms, unlike dopamine receptor-blocking neuroleptics 9

Class Effect Considerations

• The overall incidence of adverse events in ondansetron recipients is approximately 36% during chemotherapy-induced emesis studies 2
• Side-effect profiles should not be regarded as a class effect among 5-HT3 antagonists, as emerging differences exist between agents 8

Clinical Pitfalls to Avoid

• Do not use ondansetron with apomorphine, as this combination may cause significant hypotension and loss of consciousness 1
• Screen for concomitant serotonergic medications before prescribing to minimize serotonin syndrome risk 1
• Address underlying constipation before attributing worsening nausea to disease progression, as ondansetron-induced constipation can perpetuate the nausea cycle 3
• Ensure adequate hydration and correct electrolyte abnormalities before and during ondansetron therapy to minimize cardiac risks 1