Background
Just like many other medications, ondansetron can prolong the QTc interval on an electrocardiogram. In fact, the FDA released a Drug Safety Communication in 2012 recommending against IV doses > 16 mg to help limit the risk. A prospective, observational study in 40 cardiac patients (heart failure or ACS) found that ondansetron 4 mg IV prolonged the QTc interval by 19 msec for up to 2 hours after the dose (Hafermann, Drug Healthc Patient Safety 2011). A retrospective cohort study of 210 ondansetron doses in pediatric ICU patients found that the QTC interval increased to 460-500 msec in 29% and to more than 500 msec in 11% (Trivedi, Pediatr Crit Care Med 2016). Underlying electrolyte abnormalities and organ dysfunction seemed to add the most risk.
But, what about in ED patients? What is the extent of QTC prolongation and is it clinically significant? Two groups have now published on this patient population. Here’s what they found.
Study 1 (Moffett, Acad Emerg Med 2016)
Prospective, observational study of 22 ED patients given IV ondansetron 4 mg with an ECG before and after (every 2 minutes for 20 minutes).
- Mean QT increase = 20 msec
- Zero cardiac events
- Clinical significance = probably none
Study 2 (Li, Am J Health Syst Pharm 2018)
Prospective, observational study of 20 ED patients given IV ondansetron 4 mg with an ECG before and 5 minutes after.
- Mean QT increase = 16 msec
- Zero (related) cardiac events
- Clinical significance = probably none
Application to Clinical Practice
- Do we need an ECG prior to giving IV ondansetron in the ED? Probably not in most patients unless there is reason to suspect underlying QTc prolongation or other medications that prolong the QTc (either home medications or concomitantly administered medications in the ED).
- What about an ECG before a repeat ondansetron dose? It is reasonable to obtain an ECG if a second dose is given within 2 hours. If more than 2 hours later, there is probably not a need to get an ECG first unless the patient has a significant medical history or concomitant use of a QT-prolonging medication.
- A systematic review evaluating the risk of cardiac dysrhythmias with ondansetron concluded: “Current evidence does not support routine ECG and electrolyte screening before single oral ondansetron dose administration to individuals without known risk factors. Screening should be targeted to high-risk patients and those receiving ondansetron intravenously” (Freedman, Ann Emerg Med 2014). This seems a reasonable approach with respect to high-risk patients, but probably not before an IV dose in the ED patient unless they meet the high-risk criteria described in points 1 and 2 above.
Further Information
Dr. Jessica Mason and I discussed ‘Antiemetics and the QTc’ in a February 2017 EMRAP episode.
The PharmERToxGuy 
Antiemetic of choice for those with prolonged QTc?
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Thanks for your question. The safest antiemeitcs from a QTc prolongation perspective are metoclopramide, prochlorperazine, and promethazine. Trimethobenzamide is also an option.
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Thanks for this information. Can one extrapolate this information to the outpatient use of ondansetron as well, i.e. giving the patient a several day course of tablets when discharged? Also what is your antiemetic of choice for patients on psych meds such as lexapro, in which Serotonin Syndrome is a concern?
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Mark, thanks for your questions. The systematic review does address oral ondansetron therapy as well and deems it to be lower risk than IV. Regarding the serotonin syndrome concern, this is a good question. It’s difficult to quantify an individual’s risk since we know serotonin syndrome is a continuum and each person reacts differently. Most of the data is with case reports, too, so it is unknown what the true risk is. Metoclopramide and ondansetron probably have the higher risk, compared to promethazine and prochlorperazine. Since escitalopram can cause QTc prolongation, it is probably best to avoid the combination of it with ondansetron.
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My understanding is that all of these (as dopaminergic antagonists) prolonged QTc as well. I teach all my residents to consider either benzos or antihistamines (though admittedly diphenhydramine can also mildly prolong the QTc.) Am I incorrect in this understanding?
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One of the places I like to start is qtdrugs.org, which is now crediblemeds.org. You need a free registration to view the QT med list, but it is worth it. They have 4 categories:
Known risk of TdP: ondansetron, droperidol, haloperidol
Possible risk of TdP: dolasetron, granisetron, promethazine
Conditional risk of TdP: metoclopramide, diphenhydramine
Drugs to avoid in congenital long QT: no antiemetics in this category
No classification: prochlorperazine
So, metoclopramide is a good alternative, followed by prochlorperazine.
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an emergency study would not have much relevance .. but a study of importance for further risk / benefit studies and the importance of having a drug without significant side effects
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Any thoughts on 8mg vs 4mg in single dose on qtc?
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While there have not been any prospective studies in ED patients looking at the 8 mg dose, we do know that it does seem to be dose-related. This is why doses > 16 mg are no longer recommended.
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Why do you think this option is better? What are its advantages over other possibilities?
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