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Bendamustine: Drug information

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

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

Dosage guidance:

Safety: Vigorous hydration and prophylactic measures (eg, antihyperuricemic therapy) should be instituted prior to bendamustine treatment in patients at high-risk for tumor lysis syndrome. ANC should recover to ≥1,000/mm3 and platelets to ≥75,000/mm3 prior to cycle initiation.

Dosage form considerations: The injection and the reconstituted injection have different concentrations of bendamustine hydrochloride. The concentration of bendamustine hydrochloride in the solution is 25 mg/mL (Belrapzo, Bendeka, Vivimusta) and the concentration of bendamustine hydrochloride in the reconstituted solution of lyophilized powder (Treanda) is 5 mg/mL. Do not mix or combine the formulations.

Clinical considerations: 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. Refer to the protocol or institutional guidance for additional details of off-label dosing.

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 (Ref).

Chronic lymphocytic leukemia, previously untreated (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 or 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).

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 (Ref) or 90 mg/m2 on days 1 and 2 of a 21-day treatment cycle (in combination with brentuximab vedotin) for up to 6 cycles (Ref).

Lymphodepleting therapy prior to chimeric antigen receptor T-cell immunotherapy

Lymphodepleting therapy prior to chimeric antigen receptor T-cell immunotherapy (off-label use):

Prior to tisagenlecleucel:

Note: Bendamustine-based lymphodepleting therapy is indicated in patients with previous grade 4 hemorrhagic cystitis with cyclophosphamide or who demonstrate resistance to a previous cyclophosphamide-containing regimen.

IV: 90 mg/m2/day for 2 days (for relapsed or refractory diffuse large B-cell lymphoma) followed 2 to 11 days later by chimeric antigen receptor (CAR) T-cell infusion (Ref) or 90 mg/m2/day for 2 days (for relapsed or refractory follicular lymphoma) followed 2 to 6 days later by CAR T-cell infusion (Ref).

Multiple myeloma, relapsed or refractory

Multiple myeloma, relapsed or refractory (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 (Ref) 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 (Ref) or 70 mg/m2 on days 1 and 4 of a 28-day treatment cycle (in combination with bortezomib and dexamethasone) for up to 8 cycles (Ref).

Non-Hodgkin lymphomas

Non-Hodgkin lymphomas: 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, 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 (eg, follicular, marginal zone); previously untreated (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, previously untreated (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) or 90 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for cycles 1 to 3, followed by 3 cycles of rituximab with cytarabine (Ref) or 90 mg/m2 on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) during cycles 1, 3, and 5, alternating with cytarabine and rituximab in cycles 2, 4, and 6 (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) or 90 mg/m2 over 30 minutes on days 1 and 2 of a 28-day treatment cycle (in combination with rituximab) for up to 6 cycles (Ref).

Peripheral T-cell lymphoma, relapsed/refractory

Peripheral T-cell lymphoma, relapsed or refractory (off-label use): IV: 120 mg/m2 on days 1 and 2 of a 21-day treatment cycle; continue until disease progression, unacceptable toxicity, or a maximum of 6 cycles (Ref).

Waldenström macroglobulinemia

Waldenström macroglobulinemia (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 (Ref) 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 (Ref) or 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).

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

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).

Dosing: Liver 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 (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.

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 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).

Dosing: Adjustment for Toxicity: Adult

Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.

All indications:

Bendamustine Recommended Dosage Modifications for Adverse Reactions

Adverse reaction

Severity

Bendamustine dosage modification

Dermatologic toxicity (skin reaction)

Severe or progressive

Withhold or discontinue bendamustine.

Hypersensitivity/allergic reaction

Severe

Discontinue bendamustine. Do not rechallenge for ≥ grade 3 allergic reaction.

Infusion-related reaction

Grade 1 or 2

Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent bendamustine treatment cycles.

Grade 3

Consider discontinuation of bendamustine as clinically appropriate considering benefits, risks, and supportive care.

Grade 4

Discontinue bendamustine.

Progressive multifocal leukoencephalopathy

Suspected

Withhold bendamustine and perform appropriate diagnostic evaluations.

If confirmed, consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy.

Chronic lymphocytic leukemia:

Bendamustine Recommended Dosage Modifications for Adverse Reactions in Chronic Lymphocytic Leukemia (Starting Dose: 100 mg/m2 on Days 1 and 2 of a 28-Day Cycle)

Adverse reaction

Severity

Bendamustine dosage modification

Hematologic toxicity

≥ Grade 3

Reduce bendamustine dose to 50 mg/m2 on days 1 and 2 of each treatment cycle.

Recurrence of ≥ grade 3 toxicity following dose reduction: Reduce bendamustine dose to 25 mg/m2 on days 1 and 2 of each treatment cycle.

Consider dose re-escalation in subsequent cycles at the discretion of the treating physician.

Grade 4

Withhold bendamustine until resolution (ANC ≥1,000/mm3, platelets ≥75,000/mm3).

Resume bendamustine at the discretion of the treating physician; consider dose reduction.

Reduce bendamustine dose to 50 mg/m2 on days 1 and 2 of each treatment cycle.

Recurrence of ≥ grade 3 toxicity following dose reduction: Reduce bendamustine dose to 25 mg/m2 on days 1 and 2 of each treatment cycle.

Consider dose re-escalation in subsequent cycles at the discretion of the treating physician.

Nonhematologic toxicity

Clinically significant ≥ grade 2

Withhold bendamustine until resolution to ≤ grade 1.

Resume bendamustine at the discretion of the treating physician; consider dose reduction.

Clinically significant ≥ grade 3

Reduce bendamustine dose to 50 mg/m2 on days 1 and 2 of each treatment cycle.

Consider dose re-escalation in subsequent cycles at the discretion of the treating physician.

Non-Hodgkin lymphoma, indolent, relapsed or refractory:

Bendamustine Recommended Dosage Modifications for Adverse Reactions in Non-Hodgkin Lymphoma (Starting Dose: 120 mg/m2 on Days 1 and 2 of a 21-Day Cycle)

Adverse reaction

Severity

Bendamustine dosage modification

Hematologic toxicity

Grade 4

Withhold bendamustine until resolution (ANC ≥1,000/mm3, platelets ≥75,000/mm3).

Resume bendamustine at the discretion of the treating physician; consider dose reduction.

Reduce bendamustine dose to 90 mg/m2 on days 1 and 2 of each treatment cycle.

Recurrence of grade 4 toxicity following dose reduction: Reduce bendamustine dose to 60 mg/m2 on days 1 and 2 of each treatment cycle.

Nonhematologic toxicity

Clinically significant ≥ grade 2

Withhold bendamustine until resolution to ≤ grade 1.

Resume bendamustine at the discretion of the treating physician; consider dose reduction.

≥ Grade 3

Reduce bendamustine dose to 90 mg/m2 on days 1 and 2 of each treatment cycle.

Recurrence of ≥ grade 3 toxicity following dose reduction: Reduce bendamustine dose to 60 mg/m2 on days 1 and 2 of each treatment cycle.

Dosing: Older Adult

Refer to adult dosing.

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, 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, 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 kidney failure and death (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.

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Belrapzo Intravenous)

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

Solution (Bendamustine HCl Intravenous)

100 mg/4 mL (per mL): $702.00 - $977.31

Solution (Bendeka Intravenous)

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

Solution (reconstituted) (Bendamustine HCl Intravenous)

25 mg (per each): $105.00 - $480.00

100 mg (per each): $420.00 - $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.

Dosage Forms: Canada

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)

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 (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 Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 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 2023; NIOSH 2024; 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, relapsed or 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; Lymphodepleting therapy prior to chimeric antigen receptor T-cell immunotherapy; Multiple myeloma, relapsed or refractory; Non-Hodgkin lymphoma, diffuse large B-cell, relapsed or refractory; Non-Hodgkin lymphoma, indolent (eg, follicular, marginal zone), previously untreated; Non-Hodgkin lymphoma, mantle cell, previously untreated; Non-Hodgkin lymphoma, mantle cell, relapsed or refractory; Peripheral T-cell lymphoma, relapsed or refractory; Waldenström macroglobulinemia

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

Bendamustine may be confused with brentuximab vedotin, carmustine, fotemustine, lomustine.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

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.

Metabolism/Transport Effects

Substrate of BCRP, CYP1A2 (Minor), P-glycoprotein (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 drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

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

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

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

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. 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 (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

CYP1A2 Inducers (Moderate): May decrease 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 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 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 increase neutropenic effects 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 decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects 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 increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects 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 decrease therapeutic effects 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

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects 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 decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Bendamustine may increase immunosuppressive effects of Ofatumumab. Bendamustine may decrease serum concentration of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Palifermin: May increase adverse/toxic effects 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 decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of 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 increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects 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 increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects 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 Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects 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

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Reproductive Considerations

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

Adverse effects to fertility, including impaired spermatogenesis, azoospermia, and total germinal aplasia, have been observed in clinical studies. 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/hypersensitivity, 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 (Adult Data Unless Noted)

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.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Adesial | Bemux | Bendam | Bendamustina glenmark | Bendamustina gp pharm | Bendavar | Bendeka | Bendel | Bentaman | Benzimir | Endexin | Eriotib | Esevaril | Linfomustin | Mexed | Mubetin | Nalona | Queramus | Ribomustin;
  • (AT) Austria: Bendamustin accord | Bendamustin actavis | Bendamustin hikma | Bendamustin intas | Bendamustin kabi | Levact;
  • (AU) Australia: Bendamustine sandoz | Bendamustine viatris | Ribomustin;
  • (BE) Belgium: Bendamustine accord | Levact;
  • (BG) Bulgaria: Bendamustine accord | Bendamustine actavis | Bendamustine mylan | Bendamustine sandoz | Levact | Lynetoril | Ribomustin;
  • (BR) Brazil: Ribomustin;
  • (CH) Switzerland: Bendamustin accord | Bendamustin sandoz | Ribomustin;
  • (CL) Chile: Avectar | Bendamustina | Bendavar | Bendeka | Ribomustin;
  • (CN) China: Le wei xin | Treanda;
  • (CO) Colombia: Bendal | Bendamustina | Besumid | Demustin | Genstina | Leukustim | Purpulz | Ramiza | Ribomustin | Xebina;
  • (CZ) Czech Republic: Bendamustin medac | Bendamustine accord | Bendamustine glenmark | Bendamustine kabi | Bendamustine pharmagen | Ledufan | Levact;
  • (DE) Germany: Benda nc | Bendamustin accord | Bendamustin axios | Bendamustin baxter | Bendamustin beta | Bendamustin cell pharm | Bendamustin chemi | Bendamustin hexal | Bendamustin hikma | Bendamustin kabi | Bendamustin medac | Bendamustin mylan | Bendamustin omnicare | Bendamustin onkovis | Bendamustin ribosepharm | Levact | Ribomustin;
  • (DO) Dominican Republic: Ribomustin;
  • (EC) Ecuador: Bendalid | Bendam | Bendamustina | Bendamustina clorhidrato | Bendamustina hcl | Bendavar | Leukustim | Ramiza | Ribomustin;
  • (EE) Estonia: Bendamustine accord | Bendamustine medac | Bendamustine sandoz | Ribomustin;
  • (EG) Egypt: Bendamustine hydrochloride accord | Ribomustin;
  • (ES) Spain: Bendamustina accord | Bendamustina baxter | Bendamustina dr reddys | Bendamustina dr. reddy's | Bendamustina glenmark | Bendamustina Hikma | Bendamustina intas | Bendamustina kabi | Bendamustina mylan | Bendamustina tillomed | Levact;
  • (ET) Ethiopia: Bendit | Xyotin;
  • (FI) Finland: Bendamustine accord | Bendamustine Avansor | Bendamustine fresenius kabi | Bendamustine intas | Bendamustine medac | Bendamyl | Levact;
  • (FR) France: Bendamustine accord | Bendamustine fresenius kabi | Bendamustine hikma | Bendamustine medac | Bendamustine mylan | Bendamustine reddy | Levact;
  • (GB) United Kingdom: Bendamustine | Bendamustine hydrochloride accord | Levact;
  • (GR) Greece: Bendamustine accord | Bendamustine/accord | Bendamustine/actavis | Bendamustine/sandoz | Bentalya;
  • (HK) Hong Kong: Treanda;
  • (HR) Croatia: Benmak;
  • (HU) Hungary: Bendamustin aramis | Bendamustin teva | Bendamustine accord | Bendamustine onkogen | Tabinaz;
  • (ID) Indonesia: Ribomustin;
  • (IE) Ireland: Bendamustine | Levact;
  • (IN) India: Bendit | Benzz | Bimode | Leuben | Mustin | Neomustin | Nexben | Purplz | Rolanda | Zumustin;
  • (IT) Italy: Bendamustina accord | Bendamustina dr. reddy's | Bendamustina eg | Bendamustina Hikma | Bendamustina kabi | Bendamustina medac | Levact | Stinred;
  • (JO) Jordan: Ribomustin;
  • (JP) Japan: Bendamustine hydrochloride pfizer | Bendamustine hydrochloride towa | Treakisym;
  • (KR) Korea, Republic of: Bendalid | Symbenda;
  • (KW) Kuwait: Ribomustin;
  • (LB) Lebanon: Bendavival | Ribomustin;
  • (LT) Lithuania: Bendamustine accord | Bendamustine kabi | Bendamustine medac | Bendamustine sandoz;
  • (LV) Latvia: Bendamustine accord | Bendamustine kabi | Bendamustine medac | Levact;
  • (MA) Morocco: Ribomustin;
  • (MX) Mexico: Glindeka | Ribobustan | Ribomustin;
  • (MY) Malaysia: Levact | Ribomustin | Treanda;
  • (NL) Netherlands: Bendamustine | Bendamustine accord | Bendamustine Baxter | Bendamustine HCL Mylan | Bendamustine hcl teva | Levact;
  • (NO) Norway: Bendamustina kabi | Bendamustine accord | Bendamustine fresenius kabi | Levact | Ribomustin;
  • (NZ) New Zealand: Bendamustine | Ribomustin;
  • (PE) Peru: Bendam | Bendavar | Bentine | Ribomustin;
  • (PH) Philippines: Bendamustine | Ribomustin;
  • (PK) Pakistan: Bendamustine hydochloride;
  • (PL) Poland: Bendamustine accord | Bendamustine actavis | Bendamustine glenmark | Bendamustine intas | Bendamustine sandoz | Bendamustine stada | Bendamustine Zentiva | Levact | Ribomustin;
  • (PR) Puerto Rico: Belrapzo | Bendamustine HCL | Bendeka | Treanda | Vivimusta;
  • (PT) Portugal: Bendamustina accord | Bendamustina G.E.S. | Bendamustina generis | Bendamustina Hikma | Levact;
  • (PY) Paraguay: Bemux | Bendam | Bendamustina Farmaco Uruguayo | Bendamustina gebina | Bendamustina varifarma | Esevaril | Ramiza | Ribomustin;
  • (QA) Qatar: Ribomustin;
  • (RO) Romania: Bendamustina accord | Bendamustina zentiva;
  • (RU) Russian Federation: Bendamustine canon | Kovada | Ribomustin | Rozustin;
  • (SA) Saudi Arabia: Ribomustin;
  • (SE) Sweden: Bendamustin actavis | Bendamustine accord | Bendamustine fresenius kabi | Bendamustine medac | Ribovact;
  • (SG) Singapore: Bemunat | Symbenda;
  • (SI) Slovenia: Bendamustin accord | Bendamustin sandoz | Benmak | Levact;
  • (SK) Slovakia: Bendamustin medac | Bendamustine accord | Bendamustine actavis | Bendamustine glenmark | Bendamustine intas | Bendamustine kabi | Bendamustine mylan | Bendamustine pharmagen | Bendamustine sandoz | Ledufan | Levact | Lynetoril;
  • (TH) Thailand: Ribomustin;
  • (TN) Tunisia: Bemux | Levact;
  • (TR) Turkey: Beastin | Bemustu | Bendamus | Bendustine | Levact;
  • (TW) Taiwan: Innomustine | Orimustine;
  • (UA) Ukraine: Bendamustin accord | Bendamustine accord | Bendamusvista | Bentero | Ribomustin;
  • (UY) Uruguay: Bendamustina Farmaco Uruguayo | Benzimir | Ramiza | Ribomustin;
  • (ZA) South Africa: Bimode | Ribomustin | Spalbend
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