Bendamustine

IV Preparation

Available in 2 formulations, a solution and a lyophilized powder

Do not mix or combine the 2 formulations

Each formulation vial is intended for single dose only

Solution for injection (45 mg/0.5 mL or 180 mg/2 mL solution)

• Do NOT use the solution with devices containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) including closed system transfer devices (CSTDs), adapters, and syringes
• Contains N,N-dimethylacetamide (DMA), which is incompatible with devices that contain polycarbonate or ABS
• Only use a polypropylene syringe with a metal needle and polypropylene hub to withdraw and transfer solution for injection
• Polypropylene syringes are translucent in appearance
• Solution for injection must be withdrawn and transferred for dilution in a biosafety cabinet (BSC) or containment isolator using a polypropylene syringe with a metal needle and a polypropylene hub
• Aseptically transfer calculated dose amount to 500 mL 0.9% NaCl or 2.5% dextrose/0.45% NaCl infusion bag
• The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2-0.7 mg/mL
• Visually inspect the filled syringe and the prepared infusion bag to ensure the lack of visible particulate matter prior to administration; the admixture should be a clear colorless to yellow solution

Lyophilized powder vials (25 mg/vial or 100 mg/vial)

• Aseptically reconstitute each lyophilized powder vial as follows:
  • 25 mg vial: Add 5 mL of only sterile water for injection
  • 100 mg vial: Add 20 mL of only sterile water for injection
  • Shake well to yield a clear, colorless to a pale yellow solution with a bendamustine HCl concentration of 5 mg/mL
  • The lyophilized powder should completely dissolve in 5 minutes
  • The reconstituted solution must be transferred to the infusion bag within 30 minutes of reconstitution
  • If particulate matter is observed, the reconstituted product should not be used
• Futher dilution
  • Aseptically withdraw the volume needed for the required dose (based on 5 mg/mL concentration) and immediately transfer to 500 mL 0.9% NaCl or 2.5% dextrose/0.45% NaCl infusion bag
  • The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2-0.6 mg/mL
  • After transferring, thoroughly mix the contents of the infusion bag
  • Visually inspect the filled syringe and the prepared infusion bag to ensure the lack of visible particulate matter prior to administration
  • The admixture should be a clear and colorless to slightly yellow solution

IV Administration

CLL: Infuse over 30 min

NHL: Infuse over 60 min

Storage

Does not contain preservatives

Unopened vials

• Refrigerate between 2-8°C (36-46°F)
• Retain in original package until time of use to protect from light

Final admixture

• Refrigerated: Stable for 24 hr when stored under refrigerated conditions at 2-8°C (36-46°F)
• Room temperature: Stable at room temperature (15-30°C or 59-86°F) and room light for 2 hr (diluted solution for injection) or 3 hr (reconstituted and diluted lyophilized powder)
• Administration must be completed within this period

Bendamustine may be found in some form under the following brand names:

• Bendeka

• Treanda

Bendamustine is part of the drug class:

• Nitrogen mustard analogues

Common side effects of bendamustine include:

• nausea
• vomiting
• diarrhea
• fever
• heartburn
• constipation
• stomach pain or swelling
• sores or white patches in the mouth
• dry mouth
• bad taste in the mouth or difficulty tasting food
• loss of appetite
• weight loss
• headache
• anxiety
• depression
• difficulty falling asleep or staying asleep
• back, bone, joint, arm or leg pain
• dry skin
• sweating
• night sweats
• pain in the place where the medication was injected

This is not a complete list of bendamustine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of bendamustine, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. Bendamustine caused problems in animals, when a single dose was administered to pregnant animals. There are no adequate and well controlled studies in pregnant women. Bendamustine can cause harm to your unborn baby.

If you become pregnant while receiving bendamustine, contact your doctor immediately.  

Women should not become pregnant while receiving bendamustine and for 3 months after therapy has stopped. In addition, men receiving bendamustine, should use reliable contraception for the same time period. 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

• If you have an allergy to bendamustine, mannitol, or any other part of bendamustine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Kidney disease or liver disease.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with bendamustine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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Chronic lymphocytic leukemia: Treatment of chronic lymphocytic leukemia (CLL)

Non-Hodgkin lymphoma: Treatment of indolent B-cell non-Hodgkin lymphoma (NHL) which has progressed during or within 6 months of rituximab treatment or a rituximab-containing regimen

Several formulations of bendamustine are available: A liquid solution formulation (45 mg/0.5 mL and 180 mg/2 mL [Treanda] and 100 mg/4 mL [Bendeka]) and the powder for reconstitution (5 mg/mL after reconstitution [Treanda]). Concentrations, storage, and compatibility differ between formulations. Use caution when selecting bendamustine formulation for preparation and administration. Do not mix or combine the formulations.

Bendeka: Prior to administration, allow vial(s) to reach room temperature. Refrigerated vials may partially freeze while under refrigeration; do not use if particles are observed after reaching room temperature. Dilute appropriate dose in 50 mL of NS, D2.51/2NS, or D5W to a final concentration of 1.85 to 5.6 mg/mL; thoroughly mix. The resulting solution should be clear and colorless to yellow.

Treanda:

Powder for solution (for reconstitution): Reconstitute 25 mg vial with 5 mL and 100 mg vial with 20 mL of sterile water for injection to a concentration of 5 mg/mL; powder usually dissolves within 5 minutes (do not use if particulates are visible). Within 30 minutes of reconstitution, dilute appropriate dose for infusion in 500 mL NS (or D2.51/2NS) to a final concentration of 0.2 to 0.6 mg/mL; mix thoroughly. Closed-system transfer devices (CSTDs) or adaptors containing polycarbonate or acrylonitrile-butadiene-styrene (ABS) are safe to use with the lyophilized powder formulation.

Solution: Prior to administration, dilute appropriate dose (using polypropylene syringes with a metal needle and polypropylene hub) in 500 mL NS (or D2.51/2NS) to a final concentration of 0.2 to 0.7 mg/mL; resulting solution should be colorless to yellow. Bendamustine contains N,N-dimethylacetamide, which is incompatible with CSTDs, adapters, and syringes containing polycarbonate or ABS. When used to prepare or transfer the concentrated bendamustine solution into the infusion bag, the plastic components of these devices may dissolve, resulting in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]). If using a syringe to withdraw and transfer bendamustine solution from the vial into the infusion bag, only use polypropylene syringes (translucent in appearance) with a metal needle and polypropylene hub. After dilution into the infusion bag, devices containing polycarbonate or ABS (including infusion sets) may be used.

Adverse events were observed in animal reproduction studies. May cause fetal harm if administered during pregnancy. For women and men of reproductive potential, effective contraception should be used during and for 3 months after treatment.

Commonly reported side effects of bendamustine include: fever, neutropenia, skin rash, and chills. Other side effects include: febrile neutropenia, infection, pneumonia, and pruritus. See below for a comprehensive list of adverse effects.

100 mg/m2 IV on Days 1 and 2 of a 28-day cycle
Duration of Therapy: Up to 6 cycles

Comments:
-Administer this drug via IV infusion over 10 or 30 minutes; consult the manufacturer product information for specific IV infusion time period.
-Efficacy of this drug relative to first-line therapies other than chlorambucil has not been established.

Use: Treatment of chronic lymphocytic leukemia