ISSUE: The U.S. Food and Drug Administration (FDA)
is informing healthcare professionals and the public that preliminary results
from a recently completed clinical study suggest that a 32 mg single
intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and
generics) may affect the electrical activity of the heart (QT interval
prolongation), which could pre-dispose patients to develop an abnormal and
potentially fatal heart rhythm known as Torsades de Pointes.
GlaxoSmithKline (GSK) has announced changes
to the Zofran drug label to remove the 32 mg single intravenous dose. The
updated label will state that ondansetron can continue to be used in adults and
children with chemotherapy-induced nausea and vomiting at the lower intravenous
dose recommended in the drug label, a dose of 0.15 mg/kg administered every 4
hours for three doses; however, no single intravenous dose should exceed 16 mg.
Information from the new clinical study will be included in the updated drug
BACKGROUND: Zofran (ondansetron) is in a class of
medications called 5-HT3 receptor antagonists. It is used to prevent nausea and
vomiting caused by cancer chemotherapy, radiation therapy and surgery. FDA will
evaluate the final study results when available, and will work with GSK to explore
an alternative single dose regimen that is both safe and effective for the
prevention of chemotherapy-induced nausea and vomiting in adults.
RECOMMENDATION: The new information on QT prolongation does
not change any of the recommended oral dosing regimens for ondansetron.
It also does not change the recommended lower dose intravenous dosing of
ondansetron to prevent post-operative nausea and vomiting.
use of a single 32 mg intravenous dose of ondansetron should be
avoided. New information indicates that QT prolongation occurs in a
dose-dependent manner, and specifically at a single intravenous dose of 32
who may be at particular risk for QT prolongation with ondansentron are
those with congenital long QT syndrome, congestive heart failure,
bradyarrhythmias, or patients taking concomitant medications that prolong
the QT interval
abnormalities (e.g., hypokalemia or hypomagnesemia) should be corrected
prior to the infusion of ondansetron.
lower dose intravenous regimen of 0.15 mg/kg every 4 hours for three doses
may be used in adults with chemotherapy-induced nausea and vomiting.
However, no single intravenous dose of ondansetron should exceed 16 mg due
to the risk of QT prolongation.
- The new information does not change any of the
recommended oral dosing regimens for ondansetron, including the single
oral dose of 24 mg for chemotherapy induced nausea and vomiting.
Healthcare professionals and patients are encouraged to report adverse events
or side effects related to the use of this product to the FDA's MedWatch Safety
Information and Adverse Event Reporting Program:
and submit the report Online: www.fda.gov/MedWatch/report.htm
- Download form or call 1-800-332-1088 to
request a reporting form, then complete and return to the address on the
pre-addressed form, or submit by fax to 1-800-FDA-0178
Read the MedWatch safety alert, including a
link to the Drug Safety Communication, at:
U.S. Food and Drug Administration (FDA)