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Bendamustine: Drug information

Bendamustine: Drug information
(For additional information see "Bendamustine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Belrapzo;
  • Bendeka;
  • Treanda;
  • Vivimusta
Brand Names: Canada
  • NAT-Bendamustine;
  • Treanda
Pharmacologic Category
  • Antineoplastic Agent, Alkylating Agent;
  • Antineoplastic Agent, Alkylating Agent (Nitrogen Mustard)
Dosing: Adult

Note: Bendamustine is associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting. Infection prophylaxis and/or treatment may be required prior to bendamustine administration. Vigorous hydration and tumor lysis syndrome prophylactic measures (eg, antihyperuricemic therapy) should be instituted prior to bendamustine treatment in high-risk patients. ANC should recover to ≥1,000/mm3 and platelets to ≥75,000/mm3 prior to cycle initiation.

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia: 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).

Chronic lymphocytic leukemia, 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).

Chronic lymphocytic leukemia, 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

Non-Hodgkin lymphomas:

Lymphoma, diffuse large B-cell (DLBC), relapsed or refractory (off-label dosing/combination): IV: 90 mg/m2 on days 2 and 3 of a 21-day treatment cycle (cycle 1), and then 90 mg/m2 on days 1 and 2 of a 21-day treatment cycle for 5 cycles (cycles 2 through 6) (in combination with polatuzumab vedotin and rituximab) (Sehn 2020).

Lymphoma, indolent B-cell, refractory: IV: 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 (eg, follicular, marginal zone) and mantle cell; first-line treatment (off-label use): IV: 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 dosing): IV: 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): IV: 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

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

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

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl <30 mL/minute: Use is not recommended (according to the manufacturer's labeling).

Data suggest minor changes in systemic exposure may occur with mild to moderate renal impairment. Based on a pharmacokinetic study (patients receiving 120 mg/m2 for 2 days every 21 days), only slight differences in bendamustine AUC and Cmax were demonstrated in patients with mild (CrCl >50 to ≤80 mL/minute) and moderate (CrCl >30 to ≤50 mL/minute) renal dysfunction, compared to patients with normal renal function (Owen 2010). In a retrospective study of bendamustine in CLL and NHL patients with renal impairment (CrCl <40 mL/minute) compared to patients with CrCl ≥40 mL/minute, an increased incidence of grades 3/4 thrombocytopenia was noted in NHL patients with renal impairment and grades 3/4 BUN increases were higher when combining data for CLL and NHL patients, compared to those with CrCl ≥40 mL/minute. Grade 1 and 2 fatigue, nausea, and alopecia were more common in patients with renal impairment (Nordstrom 2014). Further data regarding the effects of renal impairment on systemic bendamustine exposure is necessary; however, renal impairment would not be expected to have a notable effect on bendamustine exposure due to its short half-life and minimal (~3% as unchanged drug) renal excretion (Darwish 2015).

Dosing: Hepatic Impairment: Adult

Mild impairment: A pharmacokinetic study showed only slight differences in bendamustine AUC and Cmax in patients with mild hepatic impairment (defined in the study as total bilirubin 1 to 1.5 times ULN or AST greater than ULN), compared to patients with normal hepatic function (Owen 2010).

Moderate impairment (AST or ALT 2.5 to 10 times ULN and total bilirubin 1.5 to 3 times ULN): Use is not recommended.

Severe impairment (total bilirubin >3 times ULN): Use is not recommended.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Hypersensitivity (severe allergic reaction): Discontinue bendamustine. Do not rechallenge for ≥ grade 3 allergic reaction.

Infusion reactions:

Grade 1 or 2: Consider premedication with antihistamines, antipyretics, and corticosteroids in subsequent cycles.

Grade 3: Consider discontinuing treatment.

Grade 4: Discontinue treatment.

Progressive multifocal leukoencephalopathy: Withhold bendamustine and perform appropriate diagnostic evaluations for suspected progressive multifocal leukoencephalopathy (PML). Consider discontinuation or reduction of concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Skin reaction, severe or progressive: Withhold or discontinue bendamustine treatment.

Treatment delay:

Hematologic toxicity ≥ grade 4: Delay treatment until resolves (ANC ≥1,000/mm3, platelets ≥75,000/mm3); reinitiate bendamustine with discretion (consider dose reduction).

Nonhematologic toxicity ≥ grade 2 (clinically significant): Delay treatment until resolves to ≤ grade 1; reinitiate bendamustine with discretion (consider dose reduction).

Dose modification in CLL:

Hematologic toxicity ≥ grade 3: Reduce dose to 50 mg/m2 on days 1 and 2 of each treatment cycle. For recurrent hematologic toxicity (≥ grade 3), further reduce dose to 25 mg/m2 on days 1 and 2 of the treatment cycle. Consider re-escalating dose in subsequent cycles with discretion.

Nonhematologic toxicity ≥ grade 3 (clinically significant): Reduce dose to 50 mg/m2 on days 1 and 2 of the treatment cycle. Consider re-escalating dose in subsequent cycles with discretion.

Dose modification in NHL:

Hematologic toxicity grade 4: Reduce dose to 90 mg/m2 on days 1 and 2 of each treatment cycle. For recurrent hematologic toxicity (grade 4), further reduce dose to 60 mg/m2 on days 1 and 2 of each treatment cycle.

Nonhematologic toxicity ≥ grade 3: Reduce dose to 90 mg/m2 on days 1 and 2 of the treatment cycle with discretion. For recurrent toxicity ≥ grade 3, further reduce dose to 60 mg/m2 on days 1 and 2 of each treatment cycle.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as hydrochloride:

Belrapzo: 100 mg/4 mL (4 mL) [contains polyethylene glycol (macrogol), propylene glycol]

Bendeka: 100 mg/4 mL (4 mL) [contains polyethylene glycol (macrogol), propylene glycol]

Vivimusta: 100 mg/4 mL (4 mL) [contains alcohol, usp, polyethylene glycol (macrogol)]

Generic: 100 mg/4 mL (4 mL [DSC])

Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:

Treanda: 25 mg (1 ea); 100 mg (1 ea)

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous, as hydrochloride:

Treanda: 25 mg (1 ea); 100 mg (1 ea)

Generic: 25 mg (1 ea); 100 mg (1 ea)

Administration: Adult

IV: For chronic lymphocytic leukemia, infuse over 30 minutes (Belrapzo, Treanda), 20 minutes (Vivimusta), or 10 minutes (Bendeka). For non-Hodgkin lymphoma, infuse over 60 minutes (Belrapzo, Treanda), 20 minutes (Vivimusta), or 10 minutes (Bendeka). Administration times for off-label uses/doses vary by protocol.

Consider premedication with antihistamines, antipyretics, and corticosteroids for patients with a previous grade 1 or 2 infusion reaction to bendamustine. Bendamustine is associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); antiemetics are recommended to prevent nausea and vomiting.

Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation; monitor IV site for redness, swelling, or pain.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry cold compresses for 20 minutes 4 times daily (Perez Fidalgo 2012). May be managed with sodium thiosulfate in the same manner as mechlorethamine extravasation (Schulmeister 2011).

Sodium thiosulfate 1/6 M solution (instructions for mechlorethamine): Inject subcutaneously into extravasation area using 2 mL for each mg of drug suspected to have extravasated (Perez Fidalgo 2012; Polovich 2009).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

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

Limitations of use: Efficacy relative to first-line therapies for CLL other than chlorambucil has not been established.

Non-Hodgkin lymphoma, indolent (refractory): 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.

Use: Off-Label: Adult

Hodgkin lymphoma (relapsed or refractory); Multiple myeloma (salvage therapy); Non-Hodgkin lymphoma, diffuse large B-cell (relapsed or refractory); Non-Hodgkin lymphoma, indolent (eg, follicular, marginal zone), and mantle cell; first-line treatment; Non-Hodgkin lymphoma, mantle cell (relapsed or refractory); Waldenström macroglobulinemia

Medication Safety Issues
Sound-alike/look-alike issues:

Bendamustine may be confused with brentuximab, carmustine, lomustine.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Other safety concerns:

Different formulation issues: Bendamustine is available as a liquid solution formulation (100 mg/4 mL [Belrapzo, Bendeka]) and a 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 (ISMP [Smetzer 2015]). Do not mix or combine the formulations.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.

>10%:

Cardiovascular: Peripheral edema (13%)

Dermatologic: Skin rash (8% to 16%)

Endocrine & metabolic: Dehydration (14%), weight loss (7% to 18%)

Gastrointestinal: Abdominal pain (13%), anorexia (23%), constipation (29%), decreased appetite (13%), diarrhea (9% to 37%; grades 3/4: 1% to 3%), dyspepsia (11%), nausea (20% to 75%; grades 3/4: ≤4%), stomatitis (15%; grades 3/4: <1%), vomiting (16% to 40%; grades 3/4: ≤3%)

Hematologic & oncologic: Bone marrow depression (grades 3/4: 98%), decreased hemoglobin (88% to 89%; grades 3/4: 11% to 13%), decreased neutrophils (75% to 86%; grades 3/4: 43% to 60%), decreased platelet count (77% to 86%; grades 3/4: 11% to 25%), leukopenia (61% to 94%; grades 3/4: 28% to 56%), lymphocytopenia (68% to 99%; grades 3/4: 47% to 94%)

Hepatic: Increased serum bilirubin (34%)

Nervous system: Asthenia (8% to 11%), chills (6% to 14%), dizziness (14%), fatigue (9% to 57%), headache (21%), insomnia (13%)

Neuromuscular & skeletal: Back pain (14%)

Respiratory: Cough (4% to 22%), dyspnea (16%)

Miscellaneous: Fever (24% to 34%)

1% to 10%:

Cardiovascular: Chest pain (6%), exacerbation of hypertension (3%; including hypertensive crisis), hypotension (6%), tachycardia (7%)

Dermatologic: Hyperhidrosis (5%), night sweats (5%), pruritus (5% to 6%), xeroderma (5%)

Endocrine & metabolic: Hyperglycemia (grades 3/4: 3%), hyperuricemia (7%), hypocalcemia (grades 3/4: 2%), hypokalemia (9%), hyponatremia (grades 3/4: 2%)

Gastrointestinal: Abdominal distention (5%), dysgeusia (7%), gastroesophageal reflux disease (10%), oral candidiasis (6%), upper abdominal pain (5%), xerostomia (9%)

Genitourinary: Urinary tract infection (10%)

Hematologic & oncologic: Febrile neutropenia (6%)

Hepatic: Increased serum alanine aminotransferase (grades 3/4: 3%), increased serum aspartate transaminase (grades 3/4: 1%)

Hypersensitivity: Hypersensitivity reaction (5%)

Infection: Herpes simplex infection (3%), herpes zoster infection (10%), infection (6%)

Local: Infusion-site pain (6%)

Nervous system: Anxiety (8%), depression (6%), pain (6%)

Neuromuscular & skeletal: Arthralgia (6%), limb pain (5%), ostealgia (5%)

Renal: Increased serum creatinine (grades 3/4: 2%)

Respiratory: Nasal congestion (5%), nasopharyngitis (6% to 7%), pharyngolaryngeal pain (8%), pneumonia (8%; including atypical pneumonia), sinusitis (9%), upper respiratory tract infection (10%), wheezing (5%)

Frequency not defined:

Dermatologic: Bullous rash, dermatitis, erythema of skin, skin necrosis

Gastrointestinal: Oral inflammation

Hematologic & oncologic: Hemolysis, tumor lysis syndrome

Hepatic: Hepatitis

Hypersensitivity: Infusion-related reaction, nonimmune anaphylaxis

Infection: Sepsis, septic shock

Nervous system: Drowsiness, malaise

Renal: Acute kidney injury

Respiratory: Pulmonary fibrosis

Postmarking:

Cardiovascular: Acute myocardial infarction, atrial fibrillation, heart failure, palpitations

Dermatologic: Skin carcinoma (non-melanoma; including basal cell carcinoma of skin and squamous cell carcinoma of skin), Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Nephrogenic diabetes insipidus

Hematologic & oncologic: Acute myelocytic leukemia, myelodysplastic syndrome, pancytopenia

Hepatic: Hepatotoxicity

Hypersensitivity: Anaphylaxis

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Local: Infusion-site reaction (including infusion-site irritation, local pruritus, local swelling, localized phlebitis), injection-site reaction (including injection-site phlebitis, injection-site pruritus, irritation at injection site, pain at injection site, swelling at injection site)

Nervous system: Progressive multifocal leukoencephalopathy

Respiratory: Bronchogenic carcinoma, pneumonia due to Pneumocystis jirovecii, pneumonitis

Contraindications

Known hypersensitivity (eg, anaphylactic or anaphylactoid reactions) to bendamustine or any component of the formulation. Belrapzo and Bendeka are also contraindicated in patients with hypersensitivity to polyethylene glycol 400, propylene glycol, or monothioglycerol. Vivimusta is also contraindicated in patients with hypersensitivity to polyethylene glycol 400, dehydrated alcohol, or monothioglycerol.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Myelosuppression (neutropenia, thrombocytopenia, and anemia) is a common toxicity; nadirs typically occurred in the third week of treatment. Complications due to febrile neutropenia and severe thrombocytopenia have been reported (some fatal).

• Dermatologic toxicity: Serious and fatal dermatologic toxicities, including Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, bullous exanthema, and rash have been reported. Skin reactions have been reported with monotherapy and in combination with other antineoplastic agents or allopurinol and may be progressive or worsen with continued treatment. The risk for severe skin toxicity is increased with concurrent use of allopurinol and other medications known to cause skin toxicity.

• Extravasation: Bendamustine is an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Erythema, marked swelling, and pain have been reported with extravasation.

• Hepatotoxicity: Serious and fatal cases of liver injury have been reported, usually within the first 3 months of treatment initiation. Confounding factors in some patients included combination therapy, progressive disease, and/or hepatitis B reactivation.

• Hypersensitivity/infusion reaction: Infusion reactions, which may include chills, fever, pruritus, and rash, are common. Rarely, anaphylactic and anaphylactoid reactions have occurred, particularly with the second or subsequent cycle(s).

• Infection: Pneumonia, hepatitis, sepsis, and septic shock have been reported. Fatalities due to infection have occurred. Patients with myelosuppression are more susceptible to infection. Reactivation of hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster infection may occur in patients receiving bendamustine.

• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML), which may be fatal, has been reported, primarily when bendamustine was used in combination with obinutuzumab or rituximab. Consider PML with new-onset or changes in preexisting behavioral, cognitive, or neurological signs or symptoms.

• Secondary malignancy: Malignancies (including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, bronchial cancer, and nonmelanoma skin cancer [basal and squamous cell cancer]) and premalignant diseases have been reported.

• Tumor lysis syndrome: Tumor lysis syndrome (usually occurring in the first treatment cycle) may occur as a consequence of antineoplastic treatment, including treatment with bendamustine. May lead to life-threatening acute renal failure (without intervention).

Dosage form specific issues:

• Formulations: Bendamustine is available as a liquid solution formulation (100 mg/4 mL [Belrapzo, Bendeka, Vivimusta]) and a 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.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.

Metabolism/Transport Effects

Substrate of BCRP/ABCG2, CYP1A2 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Allopurinol: May enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced. Risk C: Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

CYP1A2 Inducers (Moderate): May decrease the serum concentration of Bendamustine. Concentrations of active metabolites may be increased. Management: Consider alternatives to moderate CYP1A2 inducers during therapy with bendamustine due to the potential for decreased bendamustine plasma concentrations and reduced efficacy. Risk D: Consider therapy modification

CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification

CYP1A2 Inhibitors (Strong): May increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Management: Consider alternatives to strong CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who can become pregnant. Patients who can become pregnant should use effective contraception during therapy and for 6 months after the last bendamustine dose. Patients with partners who can become pregnant should use effective contraception during therapy and for 3 months after the last dose of bendamustine.

Adverse effects to male fertility have been observed in clinical studies. Effects include impaired spermatogenesis, azoospermia, and total germinal aplasia. Risks are increased with combination therapy. Spermatogenesis may return in some patients following remission and may occur several years after therapy has been discontinued.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to bendamustine may cause fetal harm.

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Breastfeeding Considerations

It is not known if bendamustine is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment or for 1 week after the last bendamustine dose.

Monitoring Parameters

CBC with differential and platelets (frequently; in clinical trials, blood counts were monitored weekly initially); serum creatinine; LFTs (ALT, AST, and total bilirubin; prior to and during treatment); monitor potassium and uric acid levels in patients at risk for tumor lysis syndrome. Evaluate pregnancy status prior to use in patients who can become pregnant. Monitor for signs/symptoms of infusion reactions, anaphylaxis, infection (including reactivations), dermatologic toxicity, progressive multifocal leukoencephalopathy, and tumor lysis syndrome. Monitor IV site during and after infusion. Monitor for development of secondary malignancies, including dermatologic evaluations, during and after treatment.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Bendamustine is an alkylating agent (nitrogen mustard derivative) with a benzimidazole ring (purine analog) which demonstrates only partial cross-resistance (in vitro) with other alkylating agents. It leads to cell death via single and double strand DNA cross-linking. Bendamustine is active against quiescent and dividing cells. The primary cytotoxic activity is due to bendamustine (as compared to metabolites).

Pharmacokinetics

Distribution: Vss: ~20 to 25 L

Protein binding: 94% to 96%

Metabolism: Hepatic (extensive), via CYP1A2 to active (minor) metabolites gamma-hydroxy bendamustine (M3) and N-desmethyl-bendamustine (M4); also via hydrolysis to low cytotoxic metabolites, monohydroxy bendamustine (HP1) and dihydroxy bendamustine (HP2)

Half-life elimination: Bendamustine: ~40 minutes; M3: ~3 hours; M4: ~30 minutes

Time to peak, serum: Typically at end of infusion

Excretion: Feces (~25%); urine (~50%; ~3% as active parent drug).

Clearance: ~700 mL/minute.

Pharmacokinetic note: In a pharmacokinetic study, a 10-minute infusion of Bendeka (120 mg/m2) resulted in higher maximum plasma concentrations and equivalent systemic exposure as the same dose of Treanda infused over 60 minutes.

Pricing: US

Solution (Belrapzo Intravenous)

100 mg/4 mL (per mL): $780.00

Solution (Bendeka Intravenous)

100 mg/4 mL (per mL): $742.14

Solution (reconstituted) (Treanda Intravenous)

25 mg (per each): $891.54

100 mg (per each): $3,566.16

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Alkybend (DK, FI);
  • Bemustin (LK);
  • Bendam (AR);
  • Bendamax (BD);
  • Bendamyl (FI);
  • Bendavar (CL);
  • Bendavival (LB);
  • Bendinfus (BG);
  • Bendit (IN);
  • Demustin (IL);
  • Esevaril (AR);
  • Innomustine (TW);
  • Ledufan (CZ);
  • Levact (AT, BE, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IS, IT, LU, NL, NO, PL, PT, SI, SK, TR);
  • Lynetoril (AT, CZ);
  • Mustin (IN);
  • Mustinal (FI);
  • Nivobral (IT);
  • Orimustine (TW);
  • Rhomustin (BG);
  • Ribobustan (CR, DO, GT, HN, NI, PA, SV);
  • Ribomustin (AE, AR, BH, CH, CL, CO, EG, GR, ID, IL, LB, NZ, PE, PH, TH);
  • Ribomustine (UA);
  • Ribovact (SE);
  • Symbenda (KR, SG);
  • Tabinaz (HU);
  • Treakisym (JP);
  • Treanda (GR, HK)


For country code abbreviations (show table)
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