Note: Bendamustine is associated with a moderate emetic potential (Ref); 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: IV: 100 mg/m2 on days 1 and 2 of a 28-day treatment cycle (as a single agent) for up to 6 cycles (Ref).
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 (Ref).
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 (Ref).
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) (Ref).
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 (Ref).
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 (Ref) 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 (Ref).
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 (Ref) 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) (Ref).
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 (Ref).
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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD, Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl ≥30 mL/minute: IV: No dosage adjustment necessary (Ref).
CrCl <30 mL/minute: IV: No dosage adjustment necessary (minimal excretion of active parent drug by the kidney) (Ref). Although use is not recommended according to prescribing information, studies suggest bendamustine may be used in this patient population (Ref). Incidence of grade 3/4 adverse effects may be higher, including thrombocytopenia and increased BUN. Close monitoring of blood counts and kidney function is needed (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly removed by dialysis (highly protein bound): IV: No dosage adjustment necessary. Patients may have higher risk of leukopenia and thrombocytopenia; monitor blood counts closely (Ref).
Peritoneal dialysis: Unlikely to be significantly removed by dialysis (highly protein bound): IV: No dosage adjustment necessary; patients may have higher risk of leukopenia and thrombocytopenia; monitor blood counts closely (Ref).
CRRT: IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (Ref).
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 (Ref).
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.
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 (Ref).
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.
Refer to adult dosing.
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
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.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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)
Solution Reconstituted, Intravenous, as hydrochloride:
Generic: 25 mg (1 ea); 100 mg (1 ea)
Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:
Treanda: 25 mg (1 ea); 100 mg (1 ea)
Generic: 25 mg (1 ea); 100 mg (1 ea)
Yes
Solution (Belrapzo Intravenous)
100 mg/4 mL (per mL): $780.00
Solution (Bendamustine HCl Intravenous)
100 mg/4 mL (per mL): $702.00 - $962.86
Solution (Bendeka Intravenous)
100 mg/4 mL (per mL): $742.14
Solution (reconstituted) (Bendamustine HCl Intravenous)
25 mg (per each): $156.00 - $480.00
100 mg (per each): $660.00 - $1,920.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Benvyon: 25 mg/mL (1 mL, 4 mL, 8 mL) [contains alcohol, usp, polyethylene glycol (macrogol)]
Solution Reconstituted, Intravenous, as hydrochloride:
Treanda: 25 mg (1 ea); 100 mg (1 ea)
Generic: 25 mg (1 ea); 100 mg (1 ea)
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 (Ref); 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 (Ref). May be managed with sodium thiosulfate in the same manner as mechlorethamine extravasation (Ref).
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 (Ref).
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).
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.
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
Bendamustine may be confused with brentuximab, carmustine, lomustine.
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.
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.
Substrate of BCRP/ABCG2, CYP1A2 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Allopurinol: May enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. 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
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). 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
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
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
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
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
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
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
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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.
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).
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.
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.
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).
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.
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