Bendamustine

Name: Bendamustine

Dosing & Uses

Dosage Forms & Strengths

solution for injection (Bendeka)

  • 90mg/mL (45mg/0.5mL vial; 180mg/2mL vial) (Treanda)
  • 100mg/4mL (25mg/mL) (Bendeka)

lyophilized powder single vials (Treanda)

  • 25mg
  • 100mg
  • Teva announced that Bendeka (bendamustine HCl) injection solution is now available to replace Treanda (bendamustine HCl) lyophilized powder for reconstitution
  • Teva will continue to process orders for Treanda through March 30, 2016, after which any submitted or open orders will be canceled

Chronic Lymphocytic Leukemia

100 mg/m² IV infution on days 1 & 2 of 28-day cycle, repeated for up to 6 cycles 

Dosage modifications

  • Hematologic toxicity
    • ≥Grade 3: Reduce dose to 50 mg/m² on Days 1 and 2
    • If ≥grade 3 toxicity reoccurs, reduce dose to 25 mg/m² on Days 1 and 2
  • Nonhematologic toxicity
    • Clinically significant toxicity ≥grade 3: Reduce dose to 50 mg/m² on Days 1 and 2 of each cycle
    • Dose re-escalation may be considered

Orphan designation

  • Oral dosage formulation for CLL
  • Sponsor
    • Exinda Theapeutics LLC; 8430 Rovana Circle, Suite B; Sacramento, California 95828

Non-Hodgkin Lymphoma

Indicated for treatment of indolent B-cell non-Hodgkin lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen

120 mg/m² IV infusion on days 1 and 2 of 21-day cycle repeated for up to 8 cycles 

Dosage modifications

  • Hematologic toxicity
    • Grade 4: Reduce dose to 90 mg/m² on Days 1 and 2 of each cycle
    • If grade 4 toxicity recurs, reduce dose to 60 mg/m² on Days 1 and 2 of each cycle  
  • Non-hematologic toxicity
    • ≥Grade 3: Reduce dose to 90 mg/m² on Days 1 and 2 of each cycle
    • If toxicity ≥grade 3 reoccurs, reduce dose to 60 mg/m² on Days 1 and 2 of each cycle

Renal Impairment

Mild-to-moderate: Use caution

CrCl <40 mL/min: Not recommended

Hepatic Impairment

Mild: Use caution

Moderate (AST or ALT 2.5-10 xULN and bilirubin 1.5-3 xULN): Use not recommended

Severe hepatic impairment (bilirubin >3 times ULN): Use not recommended

Mantle Cell Lymphoma (Off-label)

90 mg/m² IV days 2 and 3 of 28-day cycle in combination with rituximab for up to 4 cycles 

Safety and efficacy not established

Bendamustine Precautions

Serious side effects have been reported with bendamustine including the following:

  • Mild or serious allergic reactions. Immediately report rash, facial swelling, or difficulty breathing during or soon after infusion.
  • A decrease in white blood cells, platelets, and red blood cells. Your doctor will monitor your blood counts. Report shortness of breath, significant fatigue, bleeding, fever, or other signs of infection.
  • Bendamustine may also cause tiredness. Avoid driving any vehicle or operating any dangerous tools or machinery if they experience this side effect.
  • Nausea and Vomiting. Tell your doctor if you experience nausea, vomiting, and diarrhea. Your doctor may prescribe treatment to manage these side effects.
  • Rash. Mild rash or itching may occur during treatment with bendamustine. Immediately report severe or worsening rash or itching.
  • Harm to your unborn baby. Women should not become pregnant throughout treatment and for 3 months after treatment with bendamustine has stopped.

Do not take bendamustine if you are allergic to bendamustine or to any of its ingredients.

Inform MD

Before taking bendamustine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to bendamustine, mannitol (Osmitrol), or any other medications
  • have or have ever had kidney or liver disease
  • tell your doctor if you are pregnant or plan to become pregnant, or if you plan to father a child. You or your partner should not become pregnant while you are receiving bendamustine. You should use birth control to prevent pregnancy in yourself or your partner during your treatment with bendamustine and for 3 months afterwards. Talk to your doctor about birth control methods that will work for you. If you or your partner becomes pregnant while receiving bendamustine, call your doctor. Bendamustine can harm the fetus
  • are breastfeeding
  • you should know that bendamustine may make you tired. Do not drive a car or operate machinery until you know how this medication affects you.
  • tell your doctor if you use tobacco products. Smoking may decrease the effectiveness of this medication.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Bendamustine and Lactation

It is not known if bendamustine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and the fact harm was evident in animal studies, a choice should be made whether to stop nursing or to stop use of this medication. Women should avoid breastfeeding while receiving bendamustine. 

How is bendamustine given?

Bendamustine is injected into a vein through an IV. A healthcare provider will give you this injection.

Bendamustine is usually given for 2 days in a row every 21 to 28 days. You may receive up to 8 treatments total, depending on the condition being treated. Follow your doctor's instructions.

You may be given other medications to help prevent certain side effects of bendamustine.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when the medicine is injected.

Bendamustine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

If you have ever had hepatitis B, bendamustine can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

Uses of Bendamustine

  • It is used to treat a type of leukemia.
  • It is used to treat a type of lymphoma.
  • It may be given to you for other reasons. Talk with the doctor.

How is this medicine (Bendamustine) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as an infusion into a vein over a period of time.
  • Other drugs may be given to help with infusion side effects.
  • If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
  • Talk with your doctor before getting any vaccines. Use with bendamustine may either raise the chance of an infection or make the vaccine not work as well.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take bendamustine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to bendamustine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent
  • Antineoplastic Agent, Alkylating Agent (Nitrogen Mustard)

Dosing Adult

Note: Treanda liquid solution formulation (45 mg/0.5 mL and 180 mg/2 mL) has been discontinued in the US for more than 1 year.

Note: Bendamustine is associated with a moderate emetic potential (Basch 2011; Roila 2016); antiemetics are recommended to prevent nausea and vomiting.

Chronic lymphocytic leukemia (CLL): IV: 100 mg/m2 on days 1 and 2 of a 28-day treatment cycle (as a single agent) for up to 6 cycles (Knauf 2009; Knauf 2012)

CLL, first-line treatment (off-label dosing): IV: 90 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for up to 6 cycles (Fischer 2012)

CLL, relapsed/refractory (off-label dosing): IV: 70 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for up to 6 cycles (Fischer 2011)

Non-Hodgkin lymphomas: IV:

Lymphoma, indolent B-cell, refractory: 120 mg/m2 on days 1 and 2 of a 21-day treatment cycle (as a single agent) for up to 8 cycles (Kahl 2010)

Lymphoma, indolent B-cell, follicular, or mantle cell, first-line (off-label use): 90 mg/m2 over 30 to 60 minutes on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for up to 6 cycles (Rummel 2013) or 90 mg/m2 over 30 minutes on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for 6 to 8 cycles (Flinn, 2014)

Lymphoma, follicular, relapsed or refractory (off-label use): 90 mg/m2 over 60 minutes on days 1 and 2 of a 35-day treatment cycle (in combination with bortezomib and rituximab) for 5 cycles (Fowler 2011) or 90 mg/m2 on days 1 and 2 of a 28-day treatment cycle for 6 cycles (in combination with obinutuzumab, then followed by obinutuzumab monotherapy in patients with stable disease, complete response, or partial response after 6 cycles of combination therapy) (Sehn 2016)

Lymphoma, mantle cell, relapsed or refractory (off-label use): 90 mg/m2 over 30 minutes on days 2 and 3 of a 28-day treatment cycle (in combination with rituximab) for up to 4 cycles (Rummel 2005)

Hodgkin lymphoma, relapsed or refractory (off-label use): IV: 120 mg/m2 over 30 minutes on days 1 and 2 of a 28-day treatment cycle for up to 6 cycles (Moskowitz 2013)

Multiple myeloma, salvage therapy (off-label use): IV: 90 to 100 mg/m2 on days 1 and 2 of a 28-day treatment cycle for at least 2 cycles (Knop, 2005) or 75 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with lenalidomide and dexamethasone) for up to 8 cycles (Lentzsch 2012)

Waldenström macroglobulinemia, refractory (off-label use): IV: 90 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for 6 cycles (Treon 2011) or 90 mg/m2 over 30 minutes on days 2 and 3 of a 28-day treatment cycle (in combination with rituximab) for 4 cycles (Rummel 2005)

Storage

Bendeka:

Solution: Store intact vials between 2°C to 8°C (36°F to 46°F); protect from light. Refrigerated vials may partially freeze at the recommended storage temperature; allow to come to room temperature prior to use. Solutions for infusion should be prepared as close as possible to administration. Solutions diluted with NS or D2.51/2NS are stable for up to 24 hours when stored at 2°C to 8°C (36°F to 46°F) or for up to 6 hours when stored at 15°C to 30°C (59°F to 86°F) and room light. Solutions diluted with D5W are stable for up to 24 hours when stored at 2°C to 8°C (36°F to 46°F) or for up to 3 hours when stored at 15°C to 30°C (59°F to 86°F) and room light. Infusion must be completed within these time frames. Bendeka is a multiple-dose vial; after the first use, partially used vials are stable for up to 28 days when stored in the original carton at 2°C to 8°C (36°F to 46°F). Do not withdraw more than 6 doses from each vial.

Treanda:

Powder for solution: Prior to reconstitution, store intact vials up to 25°C (77°F); excursions are permitted up to 30°C (86°F). Protect from light. The solution in the vial (reconstituted with SWFI) is stable for 30 minutes (transfer to 500 mL infusion bag within that 30 minutes). The solution diluted in 500 mL of NS or D2.51/2NS for infusion is stable for 24 hours refrigerated (2°C to 8°C ([36°F to 46°F]) or 3 hours at room temperature (15°C to 30°C [59°F to 86°F]) and room light. Infusion must be completed within these time frames.

Solution: Store intact vials between 2°C to 8°C (36°F to 46°F); protect from light. Solutions diluted for infusion in NS or D2.51/2NS are stable for up to 24 hours when stored at 2°C to 8°C (36°F to 46°F) or for up to 2 hours when stored at 15°C to 30°C (59°F to 86°F) and room light. Infusion must be completed within these time frames.

Monitoring Parameters

CBC with differential and platelets (monitored weekly [initially] in clinical trials); serum creatinine; liver function tests (ALT, AST, and total bilirubin; prior to and during treatment); monitor potassium and uric acid levels in patients at risk for tumor lysis syndrome; monitor for infusion reactions anaphylaxis, infection (including reactivations), and dermatologic toxicity; monitor IV site during and after infusion.

Renal Dose Adjustments

-Mild to Moderate Renal Dysfunction: Use with caution.
-Severe Renal Dysfunction (CrCl less than 40 mL/min): Not recommended.

Dialysis

This drug is dialyzable to a small extent; however, no dose adjustment guidelines have been reported.

Bendamustine Pregnancy Warnings

Animal studies have revealed single intraperitoneal doses causing embryofetal lethality, increased fetal skeletal and visceral malformations, and decreased fetal body weights. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in males treated with alkylating agents, especially in combination with other drugs. Spermatogenesis may return in patients in remission, but only several years after intensive chemotherapy has been discontinued. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use during pregnancy is not recommended unless clearly necessary as this drug may cause fetal harm based on findings from animal studies. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: -Female patients should be advised to avoid becoming pregnant by using effective contraception before therapy, during treatment, and for 3 months after the last dose; male patients should be advised to use reliable contraception for the same time period. -The possibility of irreversible infertility is associated with this drug; male patients should be warned of the potential risk to their reproductive capacities and advised to consider sperm conservation prior to treatment.

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