QT Prolongation Observed with Ondansetron: A Clinical Concern?

Ondansetron is typically a first-line agent for the prevention of nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. Because these are common complaints among inpatients, it is the most frequently administered drug in US emergency departments.¹

The drug’s safety and efficacy have driven its prevalence, but concerns began to arise when the FDA issued a safety warning in 2011 regarding QT prolongation.² Although this warning was based on evidence from ondansetron 32 mg administered intravenously, the use of the lower 4-mg dose in emergency departments has come into question.

A prospective, observational, single-center cohort study conducted at Carl R. Darnall Army Medical Center in Fort Hood, Texas, recently investigated this concern.³

Patients enrolled in this study had their baseline QT interval measurements compared before and after receiving ondansetron 4 mg intravenously in the emergency department. Patients were excluded if they had received any oral or intravenous ondansetron in the 4 hours prior to enrollment, had a known allergy to ondansetron, or had altered mental status.

Patients with a potential confounding factor for QT interval prolongation were similarly excluded. Those confounding factors included: planned co-administration of any known QT interval prolongation, signs or symptoms of cardiac ischemia, known hypokalemia/hypomagnesemia, non-sinus cardiac rhythm, baseline QT interval prolongation >450 ms in men and >470 ms in women, QRS >120 mg, bundle branch block, ventricular pre-excitation, or signs of left ventricular hypertrophy with repolarization abnormalities.

Of the 22 patients included in the final analysis, ondansetron administration was associated with an increase in the QT interval by 20 ms (95% CI, 14.0 mg to 26 mg; p<0.0001). A pairwise analysis similarly demonstrated a significant prolongation of the QT interval at 6, 12, and 14 minutes. No serious cardiac adverse events occurred.

The authors concluded that while the QT interval prolongation occurred in this population, its clinical impact was questionable.

It is important to note that the observed QT prolongation was within the previously measured change of 1.6 ms to 22 ms and within the same time frame of 4 to 11 minutes after administration. Thus, this research demonstrated that ondansetron performs consistently and reliably within the populations studied.

However, the use of ondansetron in the real world includes patient who were excluded from this study—namely, those with QT prolongation risk factors. Furthermore, given that ondansetron is the most widely used drug in the emergency department, if there was a clinically significant risk of cardiac events, it would be plausible to suggest that such events would have limited the drug’s use by now.

References

1. Centers for Disease Control and Prevention. National Hospital Ambulatory Medical Care Survey: 2011 Emergency Department Summary. www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2011_ed_web_tables.pdf. Accessed January 17, 2016.

2. Food and Drug Administration. FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran), 2011. www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Accessed January 17, 2016.

3. Moffett PM, et al. Intravenous ondansetron and the QT interval in adult emergency department patients: an observational study. Acad Emerg Med. 2016 Jan;23(1):102-5. doi: 10.1111/acem.12836. Epub 2015 Dec 31.