ben-da-MUSS-teen

Therapeutic Classification: antineoplastics

Pharmacologic Classification: benzimidazoles

• Chronic lymphocytic leukemia.
• Indolent B-cell non-Hodgkin's lymphoma that has progressed during or within 6 mo of receiving rituximab or a rituximab-containing regimen.

• Damages DNA resulting in death of rapidly replicating cells.

• Decreased proliferation of leukemic cells.
• Death of lymphoma cells.

Absorption: IV administration results in complete bioavailability.

Distribution: Distributes freely into red blood cells.

Protein Binding: 94–96%.

Metabolism/Excretion: Mostly metabolized (partially by the CYP1A2 enzyme system); 90% excreted in feces; some renal elimination. Although metabolites have antineoplastic activity, levels are extremely low.

Half-life: 40 min.

(blood levels)

Contraindicated in:

• Hypersensitivity to bendamustine or mannitol
• Hypersensitivity to polyethylene glycol 400, propylene glycol, or monothioglycerol (in multidose vial)
• Severe renal impairment (CCr <30 mL/min)
• Moderate or severe hepatic impairment
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Patients at risk for tumor lysis syndrome (concurrent allopurinol recommended)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be more susceptible to adverse reactions.

Derm: drug reaction with eosinophilia and systemic symptoms (dress), stevens-johnson syndrome, toxic epidermal necrolysis, bullous exanthema, rash.

GI: hepatotoxicity, nausea, vomiting, diarrhea.

GU: ↓fertility (males).

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia.

Metab: hyperuricemia.

Neuro: fatigue, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, weakness.

Resp: cough.

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION (INCLUDING REACTIVATION OF TUBERCULOSIS, HEPATITIS B, CYTOMEGALOVIRUS, AND HERPES ZOSTER), infusion reactions, SECONDARY MALIGNANCY, TUMOR LYSIS SYNDROME.

Drug-Drug:

• CYP1A2 inhibitors, including fluvoxamine and ciprofloxacin may ↑ levels of bendamustine and ↓ levels of active metabolites; consider alternative treatments.
• CYP1A2 inducers, including omeprazole and smoking may ↓ levels of bendamustine and ↑ levels of its active metabolites; consider alternative treatments.

Chronic Lymphocytic Leukemia

• IV (Adults): 100 mg/m² on Days 1 and 2 of a 28-day cycle, up to 6 cycles.

Non-Hodgkin's Lymphoma

• IV (Adults): 120 mg/m² on Days 1 and 2 of a 21-day cycle, up to 8 cycles.

(Generic available)

• Powder for injection: 25 mg/vial; 100 mg/vial;
• Solution for injection: 25 mg/mL;

• Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia; anemia may occur; monitor for increased fatigue, dyspnea, and orthostatic hypotension.
• Monitor for symptoms of infusion reactions (fever, chills, pruritus, rash). May rarely cause severe allergic and anaphylactic reactions, especially in second and subsequent cycles. Discontinue therapy if severe reactions occur. Ask patient about symptoms suggestive of infusion reactions after first cycle of therapy. Consider using antihistamines, antipyretics, and corticosteroids in patients who previously experienced Grade 1 or 2 reactions. Consider discontinuation of therapy in patients with Grade 3 or 4 reactions.
• Assess for tumor lysis syndrome. Usually occurs during first cycle of bendamustine. May lead to acute renal failure and death. Maintain adequate volume status, close monitoring of blood chemistry, especially potassium and uric acid levels; use allopurinol during first 1–2 wk of therapy in high risk patients.
• Assess for skin reactions (rash, toxic skin reactions, bullous exanthema). Withhold or discontinue therapy if reactions are progressive or severe. If non-hematologic toxicity is Grade 3, reduce dose to 50 mg/m² on Days 1 and 2 of each cycle.
• Monitor intake and output, appetite, and nutritional intake. Assess for nausea and vomiting. Administration of an antiemetic before and during therapy and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
• Monitor IV site for redness, swelling, pain, infection, and necrosis frequently during an after infusion. Extravasation may cause erythema, marked swelling, and pain.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

• Verify negative pregnancy test prior to starting therapy.Monitor CBC with differential and platelet count before and during therapy. The hematologic nadirs occur wk 3. Recovery usually occurs in 28 days. Hold dose and notify health care professional if ANC is 1 × 10⁹/L and platelet count is 75,000 × 10⁹/L. For patients treated for chronic lymphocytic leukemia: If hematologic toxicity Grade 3, reduce dose to 50 mg/m² on Days 1 and 2. If Grade 3 or greater toxicity recurs, reduce dose to 25 mg/m² on Days 1 and 2. For patients treated for non-Hodgkin's lymphoma: If hematologic toxicity Grade 4, reduce dose to 90 mg/m² on Days 1 and 2. If Grade 4 toxicity recurs, reduce dose to 60 mg/m² on Days 1 and 2.
  • Monitor blood chemistry, especially serum potassium and uric acid before and periodically during therapy. Allopurinol may be used during first wk of therapy to prevent tumor lysis syndrome.
  • Monitor liver function tests prior to starting and periodically during therapy, especially during first 3 mo of therapy.

• High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.

IV Administration:

• Prepare solution in a biologic cabinet. Wear gloves and safety glasses while handling medication. Discard equipment in designated containers.
• Do not confuse or combine solution for injection with powder for injection. Each has a different concentration.
• Intermittent Infusion: Bendeka, Belrapzo, and Vivimusta:
  Diluent: Allow vial to reach room temperature. Withdraw volume for dose from 25 mg/mL solution and immediately transfer to 50 mL infusion bag of 0.9% NaCl, D2.5W/0.45% NaCl, or D5W (only 0.9% NaCl, D2.5W/0.45% NaCl for Belrapzo). Do not use other diluents.Concentration: Bendeka: 0.49–5.6 mg/mL; Belrapzo: 0.05–0.7 mg/mL.Mix contents of bag thoroughly. Solutions is clear and colorless to yellow; do not infuse solutions that are discolored or contain precipitate matter. Solution is stable for 24 hrs if refrigerated or up to 3 hrs at room temperature).
• Rate: Chronic Lymphocytic Leukemia: Administer 100 mg/m² over 10 min for Bendeka, over 30 min for Belrapzoand over 20 min for Vivimusta. Non-Hodgkin's lymphoma: Administer 120 mg/m²over 10 min for Bendeka, over 60 min for Belrapzo and over 20 min for Vivimusta.
• Treanda: Reconstitute with 5 mL or 20 mL of Sterile Water for Injection for 25 mg or 100 mg vial, respectively. Shake well for clear colorless to pale yellow solution; do not use solutions that are discolored or contain particulate matter.
  Diluent: Transfer reconstituted solution to infusion bag of 500 mL of 0.9% NaCl or 2.5% dextrose/0.45% NaCl within 30 min of reconstitution. Concentration: 0.2–0.6 mg/mL.Can be used if intending use of closed system transfer devices, adapters and syringes containing polycarbonate or acrylonitrile-butadiene-styrene prior to dilution in the infusion bag.
  • Diluted solution is stable for 24 hr when refrigerated or 3 hr at room temperature; administration must be completed within this period. Solution contains no preservatives; discard unused solution.
• Rate: Chronic Lymphocytic Leukemia: Administer 100 mg/m² over 30 min. Non-Hodgkin's lymphoma: Administer 120 mg/m² over 60 min.
• Additive Incompatibility: Do not admix or dilute with other solutions or medication.

• Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; lower back or side pain; difficult or painful urination; shortness of breath; fatigue; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patients to avoid alcoholic beverages and products containing aspirin or NSAIDs; may precipitate gastric bleeding.
• Instruct patient to notify health care professional immediately if symptoms of allergic reactions (rash, facial swelling, or difficulty breathing), hepatotoxicity (jaundice, anorexia, bleeding, bruising), progressive multifocal leukoencephalopathy (confusion, memory loss, trouble thinking, difficulty talking or walking, vision loss, other neurological or cognitive symptoms), or nausea, vomiting or diarrhea occur.
• May cause tiredness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
• May cause secondary malignancies. Advise patient to have regular dermatologic evaluations.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for at least 6 mo after last dose of bendamustine. Advise males with partners of reproductive potential to use effective contraceptions for at least 3 mo following completion of therapy. Advise women to avoid breastfeeding during therapy and for at least 1 wk after last dose of therapy. May impair male fertility.
• Emphasize need for periodic lab tests to monitor for side effects.

• Improvement in hematologic parameters.

Belrapzo, Bendeka, Treanda, Vivimusta

NDC Code^*

• 42367- Eagle Pharmaceuticals, Inc
  • 42367-520- BENDAMUSTINE HYDROCHLORIDE
    • 42367-520-25- 1 VIAL, MULTI-DOSE in 1 CARTON (42367-520-25) > 1 INJECTION in 1 VIAL, MULTI-DOSE

• 42367- Eagle Pharmaceuticals, Inc
  • 42367-521- BELRAPZO
    • 42367-521-25- 1 VIAL, MULTI-DOSE in 1 CARTON (42367-521-25) > 1 INJECTION in 1 VIAL, MULTI-DOSE

• 63459- Teva Pharmaceuticals USA, Inc.
  • 63459-348- Bendeka
    • 63459-348-04- 1 VIAL, MULTI-DOSE in 1 CARTON (63459-348-04) > 4 mL in 1 VIAL, MULTI-DOSE

• 63459- Cephalon, Inc.
  • 63459-390- TREANDA
    • 63459-390-08- 1 VIAL, SINGLE-DOSE in 1 CARTON (63459-390-08) > 5 mL in 1 VIAL, SINGLE-DOSE

• 63459- Cephalon, Inc.
  • 63459-391- TREANDA
    • 63459-391-20- 1 VIAL, SINGLE-DOSE in 1 CARTON (63459-391-20) > 20 mL in 1 VIAL, SINGLE-DOSE