No link seen between ondansetron and tachyarrhythmias in healthy children

Vancouver, B.C. – The antinausea and antiemetic agent ondansetron does not trigger malignant tachyarrhythmias in pediatric patients who have a healthy, native heart, suggests a retrospective cohort study presented at the annual meeting of the Pediatric Academic Societies.

Findings of the study, conducted at a large tertiary care children’s hospital and its affiliated clinics, and spanning a 6-year period, showed that the incidence of tachyarrhythmia within 24 hours after ondansetron (Zofran) administration was just 0.02%, or 1 in 6,299 patients.

Susan London/Frontline Medical News

All of the patients developing tachyarrhythmias had a preexisting cardiac diagnosis, including cardiac transplantation in some cases, and most also had other risk factors, reported lead researcher Dr. Breanne K.P. Shah, a fellow at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Madison.

The median dose of ondansetron administered was consistent with recommendations, although it ranged widely, she noted.

"Only children with cardiac diagnoses were found to have arrhythmia after ondansetron administration," Dr. Shah commented. "In subgroup analyses of patient populations who either received frequent doses or doses higher than average, such as patients in the ED or those with oncologic diagnoses, there were no documented tachyarrhythmias in the 24 hours after receiving ondansetron. It appears that these patients are at low risk."

"The findings of our study support consideration of cardiac monitoring for children with cardiac diagnoses who are receiving ondansetron. They do not support ECG screening or continuous monitoring of other pediatric populations receiving ondansetron," she concluded.

Session comoderator Dr. Julie Brown, an emergency medicine attending physician at Seattle Children’s Hospital who is with the department of pediatrics at the University of Washington, commented, "This is a really important study that I think probably illustrates the ‘creep’ of therapy from what is well studied into applications to a wider population, which is a little frightening."

"Sometimes, we come across something striking in our clinical work that prompts us to investigate a problem that could also maybe stack the deck with adverse events. So I’m wondering if you were aware of any of the identified cases before you proceeded with the retrospective study," she said.

"We were not," Dr. Shah replied, noting that the research was prompted by a 2011 Food and Drug Administration warning about potentially fatal abnormal heart rhythms in patients administered ondansetron.

In their warning about the drug, FDA "recommended avoiding use in patients with congenital long QT. Additionally, they recommended for ECG monitoring in patients with heart failure or bradyarrhythmias, patients taking other medications that can lead to QT prolongation, or patients with electrolyte abnormalities," Dr. Shah noted.

However, "to our knowledge, no pediatric studies have been done to evaluate adverse clinical outcomes with the use of ondansetron."

The researchers retrospectively studied 58,009 visits by patients aged 0-18 years in which ondansetron was administered. A total of 199,773 doses were given to 37,794 patients.

For single doses, the median dose was 4 mg (range, 0.11 to 36 mg) and the median dosage was 0.1 mg/kg per dose (range, 0.005 to 0.86 mg/kg per dose).

Overall, six patients developed a tachyarrhythmia within 24 hours of receiving ondansetron, for an incidence of 0.02%. They ranged in age from 9 weeks to 17 years, and two-thirds were male.

None died at the time of the event, according to Dr. Shah.

The average ondansetron dosage in these patients was 0.1 mg/kg per dose, and the time between dosing and onset of tachyarrhythmia ranged from 2 to 20 hours.

All six patients had underlying cardiac diagnoses (congenital conduction abnormality, congenital heart defect, cardiac tumor, or heart transplantation). And five had concomitant risk factors (use of medications known to prolong the QT interval, electrolyte abnormalities, or prolonged QTc interval).

"The retrospective nature of this study limits our ability to make conclusions," Dr. Shah acknowledged. "We used a conservative approach, assuming that any documentation of a tachyarrhythmia in the medical record within 24 hours of ondansetron constituted an ondansetron-related event, but we cannot prove cause."

Dr. Shah disclosed no relevant conflicts of interest.

Vancouver, B.C. – The antinausea and antiemetic agent ondansetron does not trigger malignant tachyarrhythmias in pediatric patients who have a healthy, native heart, suggests a retrospective cohort study presented at the annual meeting of the Pediatric Academic Societies.

Findings of the study, conducted at a large tertiary care children’s hospital and its affiliated clinics, and spanning a 6-year period, showed that the incidence of tachyarrhythmia within 24 hours after ondansetron (Zofran) administration was just 0.02%, or 1 in 6,299 patients.

Susan London/Frontline Medical News

All of the patients developing tachyarrhythmias had a preexisting cardiac diagnosis, including cardiac transplantation in some cases, and most also had other risk factors, reported lead researcher Dr. Breanne K.P. Shah, a fellow at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Madison.

The median dose of ondansetron administered was consistent with recommendations, although it ranged widely, she noted.

"Only children with cardiac diagnoses were found to have arrhythmia after ondansetron administration," Dr. Shah commented. "In subgroup analyses of patient populations who either received frequent doses or doses higher than average, such as patients in the ED or those with oncologic diagnoses, there were no documented tachyarrhythmias in the 24 hours after receiving ondansetron. It appears that these patients are at low risk."

"The findings of our study support consideration of cardiac monitoring for children with cardiac diagnoses who are receiving ondansetron. They do not support ECG screening or continuous monitoring of other pediatric populations receiving ondansetron," she concluded.

Session comoderator Dr. Julie Brown, an emergency medicine attending physician at Seattle Children’s Hospital who is with the department of pediatrics at the University of Washington, commented, "This is a really important study that I think probably illustrates the ‘creep’ of therapy from what is well studied into applications to a wider population, which is a little frightening."

"Sometimes, we come across something striking in our clinical work that prompts us to investigate a problem that could also maybe stack the deck with adverse events. So I’m wondering if you were aware of any of the identified cases before you proceeded with the retrospective study," she said.

"We were not," Dr. Shah replied, noting that the research was prompted by a 2011 Food and Drug Administration warning about potentially fatal abnormal heart rhythms in patients administered ondansetron.

In their warning about the drug, FDA "recommended avoiding use in patients with congenital long QT. Additionally, they recommended for ECG monitoring in patients with heart failure or bradyarrhythmias, patients taking other medications that can lead to QT prolongation, or patients with electrolyte abnormalities," Dr. Shah noted.

However, "to our knowledge, no pediatric studies have been done to evaluate adverse clinical outcomes with the use of ondansetron."

The researchers retrospectively studied 58,009 visits by patients aged 0-18 years in which ondansetron was administered. A total of 199,773 doses were given to 37,794 patients.

For single doses, the median dose was 4 mg (range, 0.11 to 36 mg) and the median dosage was 0.1 mg/kg per dose (range, 0.005 to 0.86 mg/kg per dose).

Overall, six patients developed a tachyarrhythmia within 24 hours of receiving ondansetron, for an incidence of 0.02%. They ranged in age from 9 weeks to 17 years, and two-thirds were male.

None died at the time of the event, according to Dr. Shah.

The average ondansetron dosage in these patients was 0.1 mg/kg per dose, and the time between dosing and onset of tachyarrhythmia ranged from 2 to 20 hours.

All six patients had underlying cardiac diagnoses (congenital conduction abnormality, congenital heart defect, cardiac tumor, or heart transplantation). And five had concomitant risk factors (use of medications known to prolong the QT interval, electrolyte abnormalities, or prolonged QTc interval).

"The retrospective nature of this study limits our ability to make conclusions," Dr. Shah acknowledged. "We used a conservative approach, assuming that any documentation of a tachyarrhythmia in the medical record within 24 hours of ondansetron constituted an ondansetron-related event, but we cannot prove cause."

Dr. Shah disclosed no relevant conflicts of interest.

Vancouver, B.C. – The antinausea and antiemetic agent ondansetron does not trigger malignant tachyarrhythmias in pediatric patients who have a healthy, native heart, suggests a retrospective cohort study presented at the annual meeting of the Pediatric Academic Societies.

Findings of the study, conducted at a large tertiary care children’s hospital and its affiliated clinics, and spanning a 6-year period, showed that the incidence of tachyarrhythmia within 24 hours after ondansetron (Zofran) administration was just 0.02%, or 1 in 6,299 patients.

Susan London/Frontline Medical News

All of the patients developing tachyarrhythmias had a preexisting cardiac diagnosis, including cardiac transplantation in some cases, and most also had other risk factors, reported lead researcher Dr. Breanne K.P. Shah, a fellow at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Madison.

The median dose of ondansetron administered was consistent with recommendations, although it ranged widely, she noted.

"Only children with cardiac diagnoses were found to have arrhythmia after ondansetron administration," Dr. Shah commented. "In subgroup analyses of patient populations who either received frequent doses or doses higher than average, such as patients in the ED or those with oncologic diagnoses, there were no documented tachyarrhythmias in the 24 hours after receiving ondansetron. It appears that these patients are at low risk."

"The findings of our study support consideration of cardiac monitoring for children with cardiac diagnoses who are receiving ondansetron. They do not support ECG screening or continuous monitoring of other pediatric populations receiving ondansetron," she concluded.

Session comoderator Dr. Julie Brown, an emergency medicine attending physician at Seattle Children’s Hospital who is with the department of pediatrics at the University of Washington, commented, "This is a really important study that I think probably illustrates the ‘creep’ of therapy from what is well studied into applications to a wider population, which is a little frightening."

"Sometimes, we come across something striking in our clinical work that prompts us to investigate a problem that could also maybe stack the deck with adverse events. So I’m wondering if you were aware of any of the identified cases before you proceeded with the retrospective study," she said.

"We were not," Dr. Shah replied, noting that the research was prompted by a 2011 Food and Drug Administration warning about potentially fatal abnormal heart rhythms in patients administered ondansetron.

In their warning about the drug, FDA "recommended avoiding use in patients with congenital long QT. Additionally, they recommended for ECG monitoring in patients with heart failure or bradyarrhythmias, patients taking other medications that can lead to QT prolongation, or patients with electrolyte abnormalities," Dr. Shah noted.

However, "to our knowledge, no pediatric studies have been done to evaluate adverse clinical outcomes with the use of ondansetron."

The researchers retrospectively studied 58,009 visits by patients aged 0-18 years in which ondansetron was administered. A total of 199,773 doses were given to 37,794 patients.

For single doses, the median dose was 4 mg (range, 0.11 to 36 mg) and the median dosage was 0.1 mg/kg per dose (range, 0.005 to 0.86 mg/kg per dose).

Overall, six patients developed a tachyarrhythmia within 24 hours of receiving ondansetron, for an incidence of 0.02%. They ranged in age from 9 weeks to 17 years, and two-thirds were male.

None died at the time of the event, according to Dr. Shah.

The average ondansetron dosage in these patients was 0.1 mg/kg per dose, and the time between dosing and onset of tachyarrhythmia ranged from 2 to 20 hours.

All six patients had underlying cardiac diagnoses (congenital conduction abnormality, congenital heart defect, cardiac tumor, or heart transplantation). And five had concomitant risk factors (use of medications known to prolong the QT interval, electrolyte abnormalities, or prolonged QTc interval).

"The retrospective nature of this study limits our ability to make conclusions," Dr. Shah acknowledged. "We used a conservative approach, assuming that any documentation of a tachyarrhythmia in the medical record within 24 hours of ondansetron constituted an ondansetron-related event, but we cannot prove cause."

Dr. Shah disclosed no relevant conflicts of interest.