The Cardiotoxic Potential of the 5-HT3 Receptor Antagonist Antiemetics: Is There Cause for Concern?

Keefe, Deborah L.

doi:10.1634/theoncologist.7-1-65

Cited by 73 publications

(60 citation statements)

References 46 publications

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“…Other antineoplastic agents, such as arsenic trioxide (AsO 3 , Trisenox), have been observed to affect QT interval duration (20). This effect is also observed with numerous nonneoplastic agents (21), including the serotonin receptor antagonist antiemetic agents commonly given to mitigate the side effects of chemotherapeutic agents (14).…”

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confidence: 99%

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Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma

Piekarz

Frye

Wright

et al. 2006

Clinical Cancer Research

230

166

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Purpose: The histone deacetylase inhibitor depsipeptide (FK228) has activity in patients with cutaneous or peripheral T-cell lymphoma. Electrocardiogram abnormalities, thought to be a class effect, were observed in preclinical animal studies and phase I testing and led to the incorporation of intensive cardiac monitoring in an ongoing efficacy trial. Patients and Methods: This report summarizes the cardiac monitoring of 42 patients enrolled and treated on a phase II trial with depsipeptide. Cardiac evaluations included serial electrocardiograms to evaluate T-wave, STsegment, and QT interval effects and serial serum cardiac troponin I levels and left ventricular ejection fraction (LVEF) evaluations to exclude myocardial damage. Results: Cardiac studies from 282 cycles and 736 doses of depsipeptide included 2,051 electrocardiograms and 161 LVEF evaluations. Although T-wave flattening (grade 1) or ST segment depression (grade 2) was observed in more than half of the electrocardiograms obtained posttreatment, these electrocardiogram abnormalities were not associated with elevation of cardiac troponin I or with altered left ventricular function. No significant changes in LVEF were observed, even in 16 patients treated for z6 months and regardless of prior anthracycline exposure. Posttreatment electrocardiograms had a mean heart rate^corrected QT interval prolongation of 14.4 milliseconds compared with baseline. Electrolyte replacement has been instituted to mitigate potential untoward effects. Conclusion: The data obtained in this study show that the administration of depsipeptide is not associated with myocardial damage or impaired cardiac function. The potential effect of heart rate^corrected QT interval prolongation remains under study.

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confidence: 99%

“…Cardiac disease in cancer patients is common and can be due to the malignancy itself, preexisting heart disease, or cardiotoxic chemotherapeutic agents (14). The most prominent heartrelated chemotherapeutic toxicity is myocardial damage that may lead to impaired cardiac function and overt congestive heart failure.…”

mentioning

confidence: 99%

Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma

Piekarz

Frye

Wright

et al. 2006

Clinical Cancer Research

230

166

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“…It is metabolized by the liver by CYP-4503A, together with other drugs (e.g., cyclophosphamide, diazepam), yet no drug interactions have been reported. 16 Granisetron is not cardiotoxic in dosages lower than 300 mg/kg. 16,17 The recommended dose of granisetron is 40 mg/kg.…”

Section: Discussionmentioning

confidence: 98%

“…16 Granisetron is not cardiotoxic in dosages lower than 300 mg/kg. 16,17 The recommended dose of granisetron is 40 mg/kg. In more than 60% of patients, this dose prevents emesis for 24 hours post chemotherapy or radiation therapy.…”

Section: Discussionmentioning

confidence: 98%

Does Granisetron Eliminate the Gag Reflex? A Crossover, Double-Blind, Placebo-Controlled Pilot Study

Barenboim

Dvoyris

Kaufman

2009

Anesthesia Progress

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Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT 3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, doubleblind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O 2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P 5 .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect.

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“…These ranged from increased PR interval, increased QRS complex duration, and increased heart rate observed with dolasetron to prolonged QT c interval and decreased heart rate observed with ondansetron. 2 Between 2011 and 2012, the US Food and Drug Administration (FDA) released a series of safety communications regarding ondansetron and the risk of prolonged QT intervals leading to torsades de pointes. Ultimately, the FDA required labeling changes to the prescribing information of ondansetron, removing the 32 mg single intravenous (IV) dose of administration and limiting the maximum single IV dose to 16 mg. 3 We report a case of bradycardia after IV administration of ondansetron in a pregnant patient followed by asystole on rechallenge.…”

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Bradycardia after Intravenous Ondansetron with Asystole on Rechallenge: A Case Report

2015

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Purpose: There have been 3 published reports (4 cases) of symptomatic sinus bradycardia occurring after intravenous (IV) administration of the selective 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonist ondansetron. We report a fifth case in which the patient developed asystole after rechallenge with ondansetron. Summary: A 36-year-old pregnant patient with no cardiac history, status post cerclage for cervical insufficiency, experienced nausea in the post ambulatory care unit after administration of morphine and indomethacin for pain. After IV administration of ondansetron, the patient's heart rate decreased to the 40s and improved spontaneously. The patient experienced a second episode of nausea, another dose of ondansetron was administered, and the patient went into asystole. Advanced cardiac life support measures were initiated and chest compressions were conducted for 3 minutes with return of spontaneous circulation. The patient was monitored overnight with no development of new cardiac arrhythmias and was discharged from the hospital in stable condition. Conclusions: Sinus bradycardia after IV administration of ondansetron was observed in a 36-year-old pregnant patient status post cerclage. On rechallenge, the patient went into asystole. This case report adds to the available literature regarding ondansetron-induced cardiac arrhythmias and the possibility of asystole upon rechallenge.

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The Cardiotoxic Potential of the 5-HT3 Receptor Antagonist Antiemetics: Is There Cause for Concern?

Cited by 73 publications

References 46 publications

Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma

Cardiac Studies in Patients Treated with Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma

Does Granisetron Eliminate the Gag Reflex? A Crossover, Double-Blind, Placebo-Controlled Pilot Study

Bradycardia after Intravenous Ondansetron with Asystole on Rechallenge: A Case Report

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