Does Zofran (ondansetron) increase the QT interval?

Does Zofran (Ondansetron) Increase QT Interval?

Yes, ondansetron (Zofran) does increase the QT interval, with ECG changes including QT interval prolongation documented in patients receiving the medication, and post-marketing cases of Torsade de Pointes have been reported. 1

Evidence of QT Prolongation

• The FDA drug label explicitly states that "Electrocardiogram (ECG) changes including QT interval prolongation have been seen in patients receiving ondansetron" and warns about post-marketing cases of Torsade de Pointes in patients using ondansetron tablets 1
• Ondansetron is specifically listed as a medication that can increase the risk of QT prolongation in multiple clinical guidelines 2
• In guidelines for non-tuberculous mycobacterial pulmonary disease management, ondansetron is identified among antiemetics that increase the risk of QT prolongation 2
• Cardiovascular guidelines note that antiemetics including 5HT3 antagonists (the class to which ondansetron belongs) can prolong the QT interval 2

Magnitude of QT Prolongation

• A prospective study found that ondansetron caused a mean prolongation of the QTc by 20 ms (95% CI = 14 to 26 ms) in adult emergency department patients 3
• In patients with cardiovascular disease and additional risk factors for torsades de pointes, ondansetron prolonged QTc by 19.3 ± 18 msec (P < 0.0001) 120 minutes after administration 4
• A recent study showed QTc prolongation peaked at 5 minutes after administration (7.9 ± 18.1 ms) and remained consistent at 15 and 30 minutes 5
• The effect appears to be dose-dependent, with 8 mg doses associated with higher rates of QTc prolongation compared to 4 mg doses 6

Risk Factors for QT Prolongation with Ondansetron

• The risk of QT prolongation is higher in patients with: 1, 7

  • Congenital long QT syndrome
  • Electrolyte abnormalities (especially hypokalemia or hypomagnesemia)
  • Congestive heart failure
  • Bradyarrhythmias
  • Patients taking other medications that prolong the QT interval

• Patients with cardiovascular disease are at particularly high risk, with 31% of heart failure patients and 46% of acute coronary syndrome patients meeting gender-related thresholds for prolonged QTc after ondansetron administration 4

Drug Interactions That Increase Risk

• Concomitant use of ondansetron with other QT-prolonging medications significantly increases the risk of QT prolongation and potential arrhythmias 1, 2
• Specific medications to avoid in combination with ondansetron include: 2
  • Antiarrhythmics (especially class IA and III)
  • Antimalarials (chloroquine, hydroxychloroquine)
  • Antipsychotics (haloperidol, droperidol)
  • Antidepressants (tricyclics, escitalopram)
  • Other antiemetics (domperidone)
  • Antiviral drugs (lopinavir/ritonavir)

Monitoring Recommendations

• ECG monitoring is recommended in patients with risk factors for QT prolongation when receiving ondansetron 1
• Baseline ECG should be obtained in all patients and electrolyte abnormalities corrected prior to starting treatment 2
• ECG should be repeated at appropriate intervals after initiation of therapy and following any dosing changes 2
• For patients receiving arsenic trioxide (which also prolongs QT) in combination with ondansetron, alternative rate-correction formulas (Fridericia, Hodges, or Sagie/Framingham) are recommended over the Bazett formula to avoid unnecessary treatment interruptions 2

Management of QT Prolongation

• Avoid ondansetron in patients with congenital long QT syndrome 1
• Consider alternative antiemetics in patients with multiple risk factors for QT prolongation 7
• If QTc reaches >500 ms or increases >60 ms from baseline: 2, 7
  • Temporarily withhold ondansetron
  • Correct electrolyte abnormalities
  • Discontinue other medications that may prolong QT interval if possible
  • Monitor via ECG until QTc returns to acceptable range

Clinical Significance

• Despite documented QT prolongation, some studies suggest the clinical impact may be questionable in patients without additional risk factors 5, 3
• No cases of cardiac arrhythmia were reported in several prospective studies of ondansetron administration in emergency department settings 5, 8
• However, in high-risk patients (cardiovascular disease with additional risk factors), the risk of clinically significant QT prolongation is substantial 4

In conclusion, ondansetron does increase the QT interval, with particular concern in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications. ECG monitoring and careful patient selection are warranted in high-risk populations.