藥物警訊（第1781期）

Ondansetron (Zofran) IV: Drug Safety Communication - QT prolongation

AUDIENCE: Oncology, Surgery, Gastroenterology

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 label.

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.

* The 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 mg.

* Patients 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

* Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia) should be corrected prior to the infusion of ondansetron.

* The 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:

* Complete 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:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHuma...

FDA提醒醫療人員與大眾，最近完成的臨床試驗初步結果顯示，使用單次靜脈注射劑量32 mg的ondansetron (Zofran()可能會使心臟QT interval porlongation，導致病人引發嚴重的心律不整，如Torsades de Pointes。

GlaxoSmithKline (GSK)藥廠已公告Zofran仿單將刪除“單次靜脈注射劑量32 mg”的建議，更新後的仿單將標示對於預防成人與小孩的化學治療引起的噁心及嘔吐，可繼續用較低劑量的ondansetron，劑量為0.15 mg/kg，每4小時1次共3劑，單次靜脈注射劑量不可超過16 mg。同時，新的臨床試驗資訊也會更新至仿單中。

Zofran是一種5-HT3 receptor antagonist，臨床上被用於預防化學治療、放射治療及手術引起的噁心及嘔吐。FDA將會評估此試驗的最終結果，且將會與GSK合作定出安全且有效 的ondansetron單次靜脈注射劑量，來預防化學治療引起的噁心及嘔吐。

建議：此項新的QT prolongation資訊並不影響任何口服ondansetron的劑量建議，也不影響預防手術引起的噁心及嘔吐的低劑量ondansetron靜脈注射建議。

．應避免使用單次靜脈注射劑量32 mg，新的資訊指出QT prolongation的發生與劑量有相關性，特別是在單次靜脈注射劑量為32 mg時易發生此不良反應。

．使用ondansetron易引發QT prolongation的高風險病人為：本身有先天性long QT症狀、先天性心衰竭、心律過慢或同時併服會引起QT interval prolongation的藥品。

．在注射ondansetron前應先校正電解質不平衡（如低血鉀及低血鎂）的情形。

．預防成人的化學治療引起的噁心及嘔吐，可使用較低劑量的ondansetron 0.15 mg/kg，每4小時1次共3劑，單次靜脈注射劑量不可超過16 mg。

．此項新的QT prolongation資訊並不影響任何口服ondansetron的劑量建議，包括預防化學治療引起的噁心及嘔吐的單次口服建議劑量24 mg。

相關訊息與連結請參考FDA網址：http://www.fda.gov/Safety/MedWatch/SafetyInformation /SafetyAlertsforHumanMedicalProducts/ucm310219.htm
[Posted 06/29/2012]

資料來源：美國FDA之藥物安全警訊
資料提供：台大醫院藥劑部