FDA Issues Drug Safety Alert for Bendamustine Hydrochloride

The U.S. Food and Drug Administration (FDA) has issued a safety alert warning healthcare professionals about use of bendamustine hydrochloride (Treanda Injection solution), which has prompted a labeling change.

Use of this medication is not compatible with closed system transfer devices (CSTD), syringes, and adapters that contain acrylonitrile-butadiene-styrene or polycarbonate.

Instead, the FDA recommends that this medication (45 mg/0.5 mL or 180 mg/2 mL solution) be used solely with polypropylene syringes containing a metal needle and a polypropylene hub.

Bendamustine hydrochloride is approved to treat patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkins lymphoma (NHL) that has progressed during or after treatment with rituximab or a rituximab-containing regimen.

Drug manufacturer Teva Pharmaceuticals has received 40 complaints about this issue since December. It recently shared these with the FDA, who also received notice regarding the compatibility issues from a pharmacist. The issues involve the following: presence of particulate matter in the IV bag post-dilution, breaking or failure of the CSTD components, and CSTD leakage.

The culprit is one of the drug’s ingredients, N-dimethylacetamide (DMA), according to Teva’s investigation.

Although serious adverse health events can occur if administered to a patient, Teva has not received any such reports.

The label change will require notice of safe preparation information.

The FDA statement listed the following recommendations for healthcare professionals:

• Health care professionals should stop using Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) with CSTDs or vial adapters and syringes containing polycarbonate or ABS.
• If using Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution):
• If a CSTD would be used with Treanda Injection (45 mg/0.5 mL or 180 mg/2 mLsolution), FDA advises health care professionals to verify with the CSTD manufacturer or Teva U.S. Medical Information (1-800-896-5855) that the CSTD is compatible with Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) prior to preparing the drug.
• FDA recommends health care professionals only use a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer Treanda Injection.  Polypropylene syringes are translucent in appearance.
• Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
• Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) must be withdrawn and transferred for dilution in a biosafety cabinet (BSC) or containment isolator and withdrawn and transferred using a polypropylene syringe with a metal needle and a polypropylene hub. 
• If using Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder):
• Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder), must be reconstituted.  If a CTSD or adaptor is to be used as supplemental protection during preparation, only use Treanda for Injection(25mg/vial or 100 mg/vial lyophilized powder) and not the solution formulation.
• Do not mix or combine the solution and lyophilized powder formulations of Treanda.

Reference:

1. U.S. Food and Drug Administration. FDA warns health care professionals not to use Treanda Injection (solution) with closed system transfer devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene [press release]. www.fda.gov. 2015 Mar 10.