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FDA warns against using Treanda Injection (solution) with closed system transfer devices, adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene; provides list of compatible devices

Updated warnings for safe preparation and handling of Treanda Injection (solution) for intravenous administration

Important safety and compatibility information for Treanda injection (solution)

[09/04/2015] On March 10, 2015, the FDA issued a statement warning health care professionals not to use chemotherapy drug Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) with closed system transfer devices (CSTDs), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).

As an update, FDA is providing information on specific devices tested by Treanda manufacturer Teva Pharmaceuticals and found compatible with Treanda injection (See Tables 1 and 2).  Treanda (bendamustine hydrochloride) is used to treat patients with chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. 

Treanda is available in two formulations: a solution, Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution); and a lyophilized powder, Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder).  The information discussed here is referring to compatibility with the solution, Treanda Injection.

Treanda Injection contains N, N-dimethylacetamide (DMA), which is incompatible with devices that contain polycarbonate or nitrile-butadiene-styrene (ABS). Devices including CSTDs, adapters, and syringes that contain polycarbonate or ABS have been shown to dissolve when they come in contact with DMA in the drug product.  This incompatibility leads to device failure such as leaking, breaking, or operational failure of CSTD components; possible product contamination; and potential serious adverse health consequences to practitioners such as skin reactions, or to patients, including the risk of small blood vessel blockage if the product is contaminated with dissolved ABS or polycarbonate.

Users should contact device manufacturers prior to use of the specific devices listed to ensure there have been no changes made to the material composition of the devices to ensure compatibility with Treanda use. 


Table 1 lists the compatibility of Treanda Injection with specific closed system transfer devices, syringes, vial adapters and gloves.

Table 1: Compatible devices for use with Treanda Injection (based on testing conducted by Teva from February 2015 through June 2015)

Component Tested

Component Brand Name (Part Number)

Closed System Transfer Devices (CSTDs)

BD Phaseal System consisting of:
BD Phaseal Protector P14 (REF 515100), BD Phaseal Injector Luer Lock N35 (REF 515003),
BD Phaseal Infusion Adapter C100 (REF 515306),
BD syringe 5 mL (REF 309646 and 309657)

Vial Adapters

Baxter CHEMO-AIDE Dispensing Pin (REF 2N9106)
Medimop Swabable Vial Adapter (REF 8070101)
Alaris Smartsite (REF 2202E and 2203E)

Polypropylene Syringes

BD (Becton Dickinson), 5 mL (REF 309646); 3 mL (REF 309657)

Covidien Monoject, 5 mL (REF 1180600777); 3 mL (REF 1180300777)

B. Braun, 5 mL (REF 4617053V-02);
3 mL (REF 4610303-02)

Air-Tite Norm Jet, 5 mL (REF 4050.X00V0) and 3 mL (REF 4020.X00V0)
Medline 5 mL (REF SYR105010) and
3 mL (REF SYR103010)
Terumo, 5 mL (REF SS-05L)

Disposable Gloves*

ChemoPlus (REF CT0194-1)
EP-Blue (REF 181350)
Jackson Safety G29 (REF 49824)
NeoPro (REF NPG-888)
NitriDerm (REF 182350)
Purple (REF 50604)
Purple KC 500 (REF 55084)
UltraSense EC (REF USE-880)

*Part numbers reflect a specific size glove used in the compatibility tests.  Brand names are trademarks of the respective manufacturer.
 

Table 2 lists the IV administration set tested and found to be compatible with Treanda Injection after dilution in a 500 mL 0.9% sodium chloride IV infusion bags.

Table 2: Compatible IV administration sets for use with Treanda injection following dilution in 500 mL 0.9% sodium chloride IV infusion bags (based on testing conducted by Teva from February 2015 through June 2015)*

Component Tested

Brand Name / Part Number

IV Administration Sets**

B. Braun Safeline (REF NF3482) and AdditIV (REF V1921)
Baxter DuoVent Spike (REF 2C7575) and Clearlink System (2H8480)
BD Phaseal Secondary set (REF 515301)
ICU Medical Clave (REF CH3011)

*Compatibility studies did not include testing with 2.5% Dextrose/0.45% Sodium Chloride Injection; however, the results of these studies are not expected to change, so either diluent, 0.9% sodium chloride or 2.5% Dextrose/0.45% Sodium Chloride Injection, can be used with Treanda injection. Teva Pharmaceuticals, Inc., the manufacturer of Treanda injection performed the compatibility testing. The recommendations for use of specific devices are provided by Teva.

** Brand names are trademarks of the respective manufacturer.

FDA required label changes (PDF) for both the solution and the powder formulations of Treanda to reflect the following information for safe preparation and handling for IV administration.

Additional Recommendations for Drug Preparation

Safe Preparation and Handling for IV Administration of Treanda Injection

  • When preparing and transferring concentrated Treanda Injection (solution) into the infusion bag, do not use devices that contain polycarbonate or ABS. However, after Treanda Injection is diluted into the infusion bag, devices that contain polycarbonate or ABS, including infusion sets, may be used.
  • Use only a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer Treanda Injection from the vial into an infusion bag.
  • If a CSTD or adapter that contains polycarbonate or ABS is used as supplemental protection prior to dilution, only use Treanda for Injection, the lyophilized powder formulation.
  • The use of gloves and safety glasses is recommended to avoid exposure in case of vial breakage or other accidental spillage. If gloves come in contact with Treanda Injection prior to or after dilution, remove gloves and follow disposal procedures. If a solution of Treanda contacts the skin, wash immediately and thoroughly with soap and water. If Treanda contacts the mucous membranes, flush thoroughly with water.

For additional details on compatibility of Treanda Injection with specific closed system transfer devices, syringes, vial adapters, gloves, and IV administration sets, please refer to Teva’s Dear Health Care Provider letter (PDF).

FDA asks health care professionals and consumers to report adverse events or quality problems associated with the use of Treanda products to FDA’s MedWatch Adverse Event Reporting program by:

  • Completing and submitting the report online at MedWatch Online Voluntary Reporting Form.
  • Downloading and completing the form (PDF), then submitting it via fax at 1-800-FDA-0178.  FDA will continue to monitor this issue.


 

[03/10/2015]  FDA is warning health care professionals not to use Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) with closed system transfer devices (CSTD), adapters, and syringes containing polycarbonate or acrylonitrile-butadiene-styrene (ABS).  CSTDs are devices that are used to prepare and administer hazardous drugs for intravenous infusion, such as chemotherapy drugs.  Most marketed CSTDs contain either polycarbonate or ABS and are not compatible with Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution). 

Treanda (bendamustine hydrochloride), manufactured by Teva, is used to treat patients with chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkins lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Treanda is available in two formulations:

  •  a solution, Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution); and
  • a lyophilized powder, Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder).

FDA is recommending health care professionals use Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) only with polypropylene syringes containing a metal needle and a polypropylene hub. If a CSTD would be used with Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution), 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. Alternatively, health care professionals can use Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder) with a CSTD.

Since December 2014, Teva has received 40 complaints of this incompatibility issue, which was recently brought to FDA’s attention.  FDA also received a notification of device incompatibility with the use of Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) from a pharmacist.  These incompatibility issues included leaking of the CSTD, breaking or operational failure of the CSTD components, and a cloudy appearance or presence of particulate matter in the intravenous (IV) bag after dilution.

Teva investigated the complaints and found that N, N-dimethylacetamide (DMA), an ingredient in Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution), is incompatible with polycarbonate or ABS.  Devices that contain polycarbonate or ABS dissolve when coming into contact with DMA.  This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.  To date, no adverse events have been reported related to this incompatibility. 

FDA is requiring label changes (PDF) for both the solution and the powder formulations of Treanda to reflect the following safe preparation information.

Recommendations for Health Care 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.

For additional details on safe preparation of either the Treanda Injection (45 mg/0.5 mL or 180 mg/2 mL solution) or Treanda for Injection (25mg/vial or 100 mg/vial lyophilized powder), please refer to Teva’s Dear Health Care Provider letter (PDF).

FDA asks health care professionals and consumers to report adverse events or quality problems associated with the use of Treanda products to FDA’s MedWatch Adverse Event Reporting program by:

  • Completing and submitting the report online at MedWatch Online Voluntary Reporting Form.
  • Downloading and completing the form (PDF), then submitting it via fax at 1-800-FDA-0178.  FDA will continue to monitor this issue.

 

 

Page Last Updated: 09/08/2015
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