Bendamustine Hydrochloride (Treanda) Injection Solution Incompatible with Most Closed System Transfer Devices - update
September 10, 2015
In March 2015, FDA issued a warning that bendamustine 90 mg/mL injection solution (Treanda – Teva) should not be used with most closed system transfer devices, adapters, or syringes. Bendamustine 90 mg/mL injection is incompatible with polycarbonate or acrylonitrile-butadiene-styrene (ABS), components of most marketed closed system transfer devices used to prepare or administer hazardous drugs. Between FDA and Teva, there have been more than 40 reports of incompatibility between bendamustine 90 mg/mL injection and closed system transfer devices.
Bendamustine 90 mg/mL injection contains N,N-dimethylacetamide (DMA), which causes dissolution of devices containing polycarbonate or ABS. Use of incompatible products may cause the closed system transfer device to leak, break, or become inoperable; may cause drug solution to appear cloudy; or may result in particulates in the drug solution. Device leaking may lead to product contamination or cause healthcare workers to be exposed to hazardous drugs. Currently, no adverse events have been reported because of this incompatibility.
Bendamustine 90 mg/mL injection is supplied in 45 mg/0.5 mL and 180 mg/2 mL vials. Prepare and administer bendamustine 90 mg/mL injection only with polypropylene syringes with a metal needle and a polypropylene hub. Do not use polycarbonate- or ABS-containing devices to prepare or transfer bendamustine injection into an infusion bag. Infusion sets containing polycarbonate or ABS can be used once bendamustine injection is diluted in the infusion bag. Teva has specifically tested the BD Phaseal closed system transfer device and found it compatible with bendamustine injection. The BD Phaseal system includes BD Phaseal Protector P14 (REF 515100), BD Phaseal Injector Luer Lock N35 (REF 515003), BD Phaseal Infusion Adapter C100 (REF 515306), and BD syringe 5 mL (REF 309646 and 309657). If use of an alternative closed system transfer device is desired, contact Teva Medical Information at 1-800-896-5855 prior to use to verify that the specific device is compatible with bendamustine injection.
Teva has also tested several vial adapters, polypropylene syringes, IV administration sets, and disposable gloves for compatibility with bendamustine injection. A list of compatible devices is available at www.fda.gov/Drugs/DrugSafety/ucm437469.htm.
Bendamustine is also supplied as lyophilized powder for injection in 25 mg or 100 mg single-dose vials, which must be reconstituted to 5 mg/mL prior to administration. Closed system transfer devices or adapters may be used for preparation and administration of solutions prepared from bendamustine lyophilized powder. Do not mix the commercially available solution with the lyophilized powder.
The bendamustine package insert has been updated to discuss this potential incompatibility and now includes information for safe preparation and use before and after dilution of bendamustine injection. Report adverse events related to the use of bendamustine injection and closed system transfer devices to the MedWatch Safety Information and Adverse Event Reporting Program at www.fda.gov/MedWatch/report. Additional information is available at the following links:
- FDA MedWatch Alert (March 10, 2015):
- FDA Statement (Updated September 4, 2015):
- Revised package insert (September 2015):
- Teva Dear Health Care Provider Letter (September 2, 2015):
September 10, 2015; March 16, 2015; University of Utah, Drug Information Service. Copyright 2015, Drug Information Service, University of Utah, Salt Lake City, UT.