bendamustine (Rx)

Brand and Other Names:Bendeka
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, ready-to-dilute solution

  • 100mg/4mL (25mg/mL) (Bendeka; generic)

injection, lyophilized powder for reconstitution

  • 25mg/single-dose vial (Treanda; generic)
  • 100mg/single-dose vial (Treanda; generic)

Chronic Lymphocytic Leukemia

100 mg/m² IV infusion on days 1 and 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

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

Dosage Modifications

Renal impairment

  • Mild-to-moderate: Use caution
  • CrCl <30 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

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Interactions

Interaction Checker

and bendamustine

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Lymphopenia (68-99%)

            Leukopenia (61-94%; grade 3/4, 28-56%)

            Anemia (88-89%; grades 3/4 11-13%)

            Thrombocytopenia (77-86%; grade 3/4, 11-25%)

            Neutropenia (75-86%; grade 3/4, 43-60%)

            Nausea (20-75%)

            Fatigue (9-57%)

            Vomiting (16-40%)

            Diarrhea (9-37%)

            Bilirubin increased (<34%; grade 3/4, 3%)

            Constipation (<29%)

            Fever (24-34%)

            Pyrexia (24%)

            Anorexia (<23%)

            Cough (4-22%)

            Headache (<21%)

            Weight loss (7-18%)

            Dehydration (<16%)

            Rash (8-16%)

            Stomatitis (<15%)

            Back pain (<14%)

            Dizziness (<14%)

            Chills (6-14%)

            Peripheral edema (13%)

            Abdominal pain (5-13%)

            Insomnia (<13%)

            Dyspepsia (<11%)

            Weakness (8-11%)

            1-10%

            Upper respiratory infection (10%)

            Gastroesophageal reflux disease (<10%)

            Urinary tract infection (<10%)

            Xerostomia (9%)

            Hypokalemia (<9%)

            Anxiety (8%)

            Hyperuricemia (<7%)

            Tachycardia (<7%)

            Taste alteration (<7%)

            Arthralgia (<6%)

            Chest pain (<6%)

            Depression (<6%)

            Hypotension (<6%)

            Injection site pain (<6%)

            Pain (<6%)

            Pruritus (5-6%)

            Febrile neutropenia (3-6%)

            Rash (5%)

            Postmarketing Reports

            Injection or infusion site reactions including phlebitis

            Blood and lymphatic systems disorders: Pancytopenia, myelosuppression

            Cardiovascular disorders: Atrial fibrillation, congestive heart failure (some fatal), myocardial infarction (some fatal), palpitation

            General disorders and administration site conditions: Injection site reactions (including irritation, swelling), infusion site reactions (including pruritus, irritation, swelling)

            Immune system disorders: Anaphylaxis Infections and infestations: Pneumocystis jiroveci pneumonia

            Respiratory, thoracic and mediastinal disorders: Pneumonitis

            Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome (with concomitant allopurinol and other medications known to cause the syndrome), toxic epidermal necrolysis (with concomitant allopurinol and other medications known to cause the condition), drug reaction with eosinophilia and systemic symptoms (DRESS)

            Tumor lysis syndrome

            Skin reactions

            Hepatotoxicity

            Other malignancies

            Extravasation Injury

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            Warnings

            Contraindications

            Hypersensitivity to bendamustine or mannitol

            Atrial fibrillation, congestive heart failure (some fatal), myocardial infarction (some fatal), palpitation

            Cautions

            Interrupt if severe infusion reactions

            Mild-mod renal impairment, mild hepatic impairment

            Possibility of anaphylactic/infusion reactions: severe in rare cases

            Myelosuppression may occur; delay or reduce dose; restart treatment based on ANC and platelet count recovery; complications of myelosuppression may lead to death

            Monitor for fever and other signs of infection and treat promptly

            Severe infusion and anaphylactic reactions reported; monitor clinically and discontinue therapy; premedicate in subsequent cycles for milder reactions

            Tumor lysis syndrome reported; acute renal failure and death may occur; anticipate and use supportive measures

            Fatal and serious skin reactions have been reported with bendamustine treatment in clinical trials and postmarketing safety reports, including toxic skin reactions [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema, and rash; events occurred when given as a single agent and in combination with other anticancer agents or allopurinol; monitor patients with skin reactions closely; if skin reactions are severe or progressive, withhold or discontinue bendamustine hydrochloride injection

            Premalignant and malignant diseases reported

            Tumor lysis syndrome reported with use; onset tends to be within first treatment cycle of bendamustine hydrochloride and, without intervention, may lead to acute renal failure and death; preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels

            Fatal and serious cases of liver injury reported with bendamustine hydrochloride injection

            Monitor liver chemistry tests prior to and during treatment

            Erythema and marked swelling can occur with extravasation; assure good venous access and monitor infusion site during and after administration

            Fetal harm can occur when administered to a pregnant woman; women should be advised to avoid becoming pregnant when receiving bendamustine

            Increased risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster; patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration

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            Pregnancy & Lactation

            Pregnancy

            There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; advise pregnant women of potential risk to fetus

            Pregnancy testing recommended for females of reproductive potential prior to initiation of therapy

            Contraception

            • Therapy can cause embryo-fetal harm when administered to pregnant women;
            • advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after final dose
            • Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with drug and for at least 3 months after final dose

            Infertility

            • Based on findings from clinical studies, therapy may impair male fertility; impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs; in some instances spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued; advise patients of potential risk to their reproductive capacities
            • Based on findings from animal studies, drug may impair male fertility due to an increase in morphologically abnormal
            • Spermatozoa; the long-term effects of therapy on male fertility, including the reversibility of adverse effects, have not been studied

            Animal data

            • In animal reproduction studies, intraperitoneal administration to pregnant mice and rats during organogenesis at doses 0.6-1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth

            Lactation

            There are no data on presence of drug or metabolites in either human or animal milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions in breastfed child, advise patients that breastfeeding is not recommended during treatment and for at least 1 week after the last dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Alkylating agent that cross-links single or double DNA strands resulting in DNA breakdown; cell cycle-nonspecific

            Pharmacokinetics

            Protein Bound: 94-96%

            Vd: 25 L

            Half-Life: 40 min

            Metabolism: CYP1A2 (low amount)

            Time to peak (serum): At end of infusion

            Excretion: Feces (90%); urine (1-10%)

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            Administration

            IV Preparation

            Available in 2 formulations, a ready-to-dilute solution that requires further dilution, and a lyophilized powder that requires reconstitution and then further dilution

            Do not mix or combine the 2 formulations

            Each formulation vial is intended for single dose only

            Ready-to-dilute solution for injection

            • Aseptically withdraw the volume needed for the required dose from the 25 mg/mL solution and immediately transfer the solution to a 50 mL infusion bag of 0.9% NaCl, 2.5% dextrose/0.45% NaCl, or 5% dextrose
            • Final concentration following dilution should be within 1.85-5.6 mg/mL
            • After transferring, thoroughly mix the contents of the infusion bag
            • The admixture should be a clear, and 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
            • Further 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
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.