Brand names: Belrapzo, Bendeka, Treanda
Drug class: Antineoplastic Agents
VA class: AN100
Chemical name: 1H-Benzimidazole-2-butanoic acid, 5-[bis(2-chloroethyl)amino]-1-methyl, monohydrochloride
Molecular formula: C₁₆H₂₁Cl₂N₃O₂ • HCl
CAS number: 3543-75-7

Medically reviewed by Drugs.com on Aug 7, 2023. Written by ASHP.

Introduction

Antineoplastic agent; nitrogen mustard-derivative alkylating agent and purine analog.^{1 2 3 4 6 7 8 12 13}

Uses for Bendamustine

Chronic Lymphocytic Leukemia

Treatment of chronic lymphocytic leukemia (CLL)^{1 2 3 21 23} (designated an orphan drug by FDA for this use).¹⁰

Prolonged progression-free survival and increased overall response rate observed with bendamustine compared with chlorambucil in patients with previously untreated, Binet stage B or C (Rai stages I–IV) CLL.^{1 2 3 4 9 21 23} Incidence of adverse effects generally also higher with bendamustine than with chlorambucil.^{1 4 21 23}

Efficacy of bendamustine relative to first-line therapies other than chlorambucil not established.^{1 2 21 23}

Non-Hodgkin’s Lymphoma

Treatment of rituximab-refractory, indolent, B-cell non-Hodgkin’s lymphoma (NHL).^{1 21 23 10004 10005}

Use in combination with rituximab^{† [off-label]} for treatment of previously untreated^{† [off-label]} advanced-stage indolent NHL or for treatment of previously untreated advanced-stage mantle cell lymphoma^{† [off-label]} is a reasonable choice (accepted, with possible conditions); however, consider histologic subtype of NHL when selecting a combination chemotherapy regimen.^{10001 10018 10019}

Use in combination with rituximab^{† [off-label]} for treatment of relapsed or refractory^{† [off-label]} indolent NHL or for treatment of relapsed or refractory mantle cell lymphoma^† is recommended (accepted).^{10002 10003 10020}

Related/similar drugs

Imbruvica, Tecvayli, Venclexta, methotrexate, rituximab, cyclophosphamide, Revlimid

Bendamustine Dosage and Administration

General

• To minimize risk of infusion-related reactions in patients who have previously experienced grade 1 or 2 infusion reactions, consider premedication with an antihistamine, antipyretic, and corticosteroid during subsequent treatment cycles.^{1 21 23} (See Infusion Reactions and Anaphylaxis under Cautions.)

• To minimize the risk of tumor lysis syndrome, take appropriate measures (e.g., adequate hydration) during therapy.^{1 21 23} (See Tumor Lysis Syndrome under Cautions.)

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.^{1 21 23}

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.^{1 21 23}

Handle cautiously; use protective equipment (e.g., gloves, safety glasses) to minimize risk of exposure.^{1 21 23} If skin or mucosal contact occurs, immediately and thoroughly wash skin with soap and water and flush mucosa with water.^{1 21 23} Manufacturer states that gloves should be removed and discarded (per usual procedures for handling cytotoxic drugs) if contact with undiluted Belrapzo occurs.²³

Avoid extravasation.^{1 21 23} Ensure good venous access prior to administration; monitor infusion site for erythema, swelling, pain, infection, and necrosis during and after administration.^{1 21 23} (See Local Effects under Cautions.)

Commercially available as injection concentrate (Bendeka, Belrapzo) and lyophilized powder (Treanda).^{1 21 23}

Lyophilized powder must be reconstituted and then diluted to prepare final infusion solution.^{1 23} Injection concentrate must be diluted prior to IV administration.^{21 23}

Dilution of Injection Concentrate (Belrapzo)

Injection concentrate is bacteriostatic; may use vial for up to 6 dose withdrawals.²³ (See Storage under Stability.)

Injection concentrate contains no preservatives; infusion solution preferably should be prepared immediately before use.²³ Discard any unused portions of the diluted infusion solution.²³

Injection concentrate may partially freeze when refrigerated.²³ Allow vial to warm to room temperature prior to dilution.²³ Do not use if particulate matter is visible after solution has reached room temperature.²³

Withdraw appropriate dose of injection concentrate from the vial (containing 25 mg/mL) and further dilute immediately in an infusion bag containing 500 mL of 0.9% sodium chloride or 2.5% dextrose and 0.45% sodium chloride to a final concentration of 0.2–0.7 mg/mL.²³

Administration must be completed within 24 hours of dilution when diluted solution is stored under refrigeration or within 3 hours when stored at room temperature under normal room light conditions.²³ (See Storage under Stability.)

Dilution of Injection Concentrate (Bendeka)

Injection concentrate is bacteriostatic; may use vial for up to 6 dose withdrawals.²¹ (See Storage under Stability.)

Injection concentrate contains no preservatives; infusion solution preferably should be prepared immediately before use.²¹ Discard any unused portions of the diluted infusion solution.²¹

Injection concentrate may partially freeze when refrigerated.²¹ Allow vial to warm to room temperature prior to dilution.²¹ Do not use if particulate matter is visible after solution has reached room temperature.²¹

Withdraw appropriate dose of injection concentrate from the vial (containing 25 mg/mL) and further dilute immediately in an infusion bag containing 50 mL of 0.9% sodium chloride, 2.5% dextrose and 0.45% sodium chloride, or 5% dextrose injection to a final concentration of 1.85–5.6 mg/mL.²¹

Administration must be completed within 24 hours of dilution when diluted solution (in 0.9% sodium chloride or 2.5% dextrose and 0.45% sodium chloride injection) is stored under refrigeration or within 6 hours when stored at room temperature under normal room light conditions.²¹ (See Storage under Stability.)

Administration must be completed within 24 hours of dilution when diluted solution (in 5% dextrose injection) is stored under refrigeration or within 3 hours when stored at room temperature under normal room light conditions.²¹ (See Storage under Stability.)

Reconstitution and Dilution of Lyophilized Powder for Injection (Treanda)

Reconstitute vial containing 25 or 100 mg of bendamustine hydrochloride powder with 5 or 20 mL of sterile water for injection, respectively, to provide a solution containing 5 mg/mL.¹

Shake well to ensure complete dissolution;¹ lyophilized powder should dissolve within 5 minutes.¹ Must be diluted further before IV administration.¹

Reconstituted solution contains no preservatives; solution preferably should be prepared immediately before use.¹ Discard any unused portions.¹

Within 30 minutes of reconstitution, withdraw appropriate volume of reconstituted solution from the vial and further dilute immediately in 500 mL of either 0.9% sodium chloride injection or 2.5% dextrose and 0.45% sodium chloride injection to a final concentration of 0.2–0.6 mg/mL.¹ Mix thoroughly.¹

Administration must be completed within 24 hours of dilution when diluted solution is stored under refrigeration or within 3 hours when stored at room temperature under normal room light conditions.¹ (See Storage under Stability.)

Rate of Administration

In patients with CLL, administer by IV infusion over 30 minutes (Treanda, Belrapzo) or 10 minutes (Bendeka).^{1 21 23}

In patients with rituximab-refractory, indolent, B-cell NHL, administer by IV infusion over 60 minutes (Treanda, Belrapzo) or 10 minutes (Bendeka).^{1 21 23}

In patients with untreated^† or relapsed/refractory^† indolent NHL or untreated or relapsed/refractory mantle cell lymphoma^†, bendamustine has been infused IV over 30–60 minutes.^{10001 10002 10003 10018}

Dosage

Available as bendamustine hydrochloride; dosage expressed in terms of the salt.^{1 21 23}

Adults

Chronic Lymphocytic Leukemia

IV

100 mg/m² on days 1 and 2 of each 28-day cycle, for up to 6 cycles.^{1 5 21 23}

Dosage Modification for Toxicity in CLL

IV

If toxicity occurs, delay initiation of next treatment cycle until blood counts have recovered to recommended values (ANC ≥1000/mm³ and platelet count ≥75,000/mm³) and nonhematologic toxicity has improved to grade 1 or better.^{1 21 23}

If grade 4 hematologic toxicity occurs, interrupt therapy.^{1 21 23} When blood counts improve (ANC ≥1000/mm³ and platelet count ≥75,000/mm³), resume therapy at clinician’s discretion.^{1 21 23} For grade 3 or 4 hematologic toxicity, reduce dosage to 50 mg/m² on days 1 and 2 of each treatment cycle.^{1 21 23} If grade 3 or 4 toxicity recurs, further reduce dosage to 25 mg/m² on days 1 and 2 of each cycle.^{1 21 23} Re-escalation of dosage in subsequent cycles may be considered.^{1 21 23}

If clinically important grade 2 or greater nonhematologic toxicity occurs, interrupt therapy; when toxicity improves to grade 1 or better, resume therapy at clinician’s discretion.^{1 21 23} If nonhematologic toxicity was grade 3 or 4, reduce subsequent dosage to 50 mg/m² on days 1 and 2 of each treatment cycle.^{1 21 23} Re-escalation of dosage in subsequent cycles may be considered.^{1 21 23}

Non-Hodgkin’s Lymphoma

Rituximab-refractory, Indolent, B-cell NHL

IV

120 mg/m² on days 1 and 2 of each 21-day cycle, for up to 8 cycles.^{1 21 23 10004}

Dosage Modification for Toxicity in Rituximab-refractory, Indolent, B-cell NHL

IV

If toxicity occurs, delay initiation of next treatment cycle until blood counts have recovered to recommended values (ANC ≥1000/mm³ and platelet count ≥75,000/mm³) and nonhematologic toxicity has improved to grade 1 or better.^{1 21 23}

If grade 4 hematologic toxicity occurs, interrupt therapy.^{1 21 23} When blood counts improve (ANC ≥1000/mm³ and platelet count ≥75,000/mm³), resume therapy at clinician’s discretion; reduce dosage to 90 mg/m² on days 1 and 2 of each treatment cycle.^{1 21 23} If grade 4 toxicity recurs, further reduce dosage to 60 mg/m² on days 1 and 2 of each cycle.^{1 21 23}

If clinically important grade 2 or greater nonhematologic toxicity occurs, interrupt therapy; when toxicity improves to grade 1 or better, resume therapy at clinician’s discretion.^{1 21 23} If nonhematologic toxicity was grade 3 or 4, reduce subsequent dosage to 90 mg/m² on days 1 and 2 of each treatment cycle.^{1 21 23} If grade 3 or 4 toxicity recurs, further reduce dosage to 60 mg/m² on days 1 and 2 of each cycle.^{1 21 23}

Previously Untreated† Advanced-stage Indolent NHL or Previously Untreated Advanced-stage Mantle Cell Lymphoma†

IV

90 mg/m² has been administered on days 1 and 2 of a 28-day cycle for up to 8 cycles, in combination with rituximab^† (375 mg/m² IV on day 1).^{10001 10018}

Relapsed or Refractory† Indolent NHL or Relapsed or Refractory Mantle Cell Lymphoma†

IV

90 mg/m ² has been administered on days 2 and 3 of a 28-day cycle for a total of 4–6 cycles, in combination with rituximab^† (375 mg/m² IV on day 1).^{10002 10003} An additional dose of rituximab has been administered one week prior to the first bendamustine-rituximab treatment cycle and repeated at 28 days following the last bendamustine-rituximab treatment cycle.^{10002 10003}

Special Populations

Hepatic Impairment

Avoid use in patients with hepatic impairment with serum AST or ALT concentration of 2.5–10 times the ULN and total serum bilirubin concentration of 1.5–3 times the ULN or those with total bilirubin concentration >3 times the ULN.^{1 21 23} (See Hepatic Impairment under Cautions.)

Renal Impairment

Avoid use in patients with severe renal impairment.^{1 21 23} (See Renal Impairment under Cautions.)

Geriatric Patients

No special dosage recommendations.^{1 21 23}

Cautions for Bendamustine

Contraindications

• Known history of hypersensitivity (e.g., anaphylactic or anaphylactoid reaction) to bendamustine or any ingredient in the formulation.^{1 21 23}

Warnings/Precautions

Hematologic Effects

Risk of severe (grade 3 or 4) and potentially fatal myelosuppression, manifested primarily as lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.^{1 21 23} Neutropenic sepsis, diffuse alveolar hemorrhage, and cytomegalovirus (CMV) pneumonia reported.^{1 21 23}

Monitor CBCs (i.e., leukocytes, platelets, hemoglobin, neutrophils) frequently;^{1 21 23} in clinical trials, blood counts were monitored weekly initially.^{1 21 23}

Hematologic nadirs occur during the third week of the treatment cycle; dose delays and/or dosage reductions may be required if recovery to recommended values (i.e., ANC ≥1000/mm³ and platelet count ≥75,000/mm³) has not occurred prior to initiation of the next cycle of therapy.^{1 21 23} (See Dosage under Dosage and Administration.)

Infectious Complications

Infections (e.g., pneumonia, sepsis, hepatitis) resulting in septic shock and death have occurred in adults and pediatric patients.^{1 21 23} Increased risk of infection in patients with myelosuppression.^{1 21 23} (See Hematologic Effects under Cautions.)

Increased risk of reactivation of infections (e.g., HBV infection, CMV infection, tuberculosis, herpes zoster).^{1 21 23}

Institute appropriate monitoring and measures to prevent reactivation of infections prior to initiation of therapy.^{1 21 23} If reactivation occurs, institute appropriate anti-infective therapy.^{1 21 23}

Infusion Reactions

Infusion reactions (e.g., fever, chills, pruritus, rash) occur commonly.^{1 21 23} Severe anaphylactic and anaphylactoid reactions reported rarely, mainly in the second and subsequent cycles of therapy.^{1 21 23}

Monitor patients clinically; discontinue therapy if a severe reaction occurs.^{1 21 23} After the first cycle of therapy, ask the patient about symptoms suggestive of infusion reactions.^{1 21 23}

If grade 1 or 2 infusion reactions occur, consider a premedication regimen (e.g., antihistamine, antipyretic, and corticosteroid) during subsequent treatment cycles.^{1 21 23}

If grade 4 infusion reactions occur, discontinue therapy.^{1 21 23} If clinically appropriate, consider discontinuing therapy if grade 3 infusion reactions occur.^{1 21 23}

If grade 3 or worse allergic-type reactions occur, permanently discontinue therapy.^{1 21 23}

Tumor Lysis Syndrome

Tumor lysis syndrome reported, generally during the first cycle of therapy; without appropriate intervention, acute renal failure and death may occur.^{1 21 23}

Closely monitor blood chemistries (particularly potassium and uric acid concentrations) and take appropriate measures (e.g., adequate hydration) to prevent tumor lysis syndrome.^{1 21 23}

Concomitant allopurinol therapy may increase the risk of severe skin reactions.^{1 21 23} (See Dermatologic Reactions under Cautions.)

Dermatologic Reactions

Possible dermatologic reactions (e.g., rash, toxic skin reactions [Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms {DRESS}], bullous exanthema);^{1 21 23} may be progressive and increase in severity with continued therapy.^{1 21 23}

Monitor closely if dermatologic reactions occur; if reaction is severe or progressive, withhold or discontinue bendamustine.^{1 21 23}

Hepatic Toxicity

Liver injury, sometimes fatal or serious, reported, although confounding factors (e.g., concomitant use of other antineoplastic agents, progressive disease, reactivation of HBV) reported in some cases.^{1 21 23} Generally occurs during initial 3 months of therapy.^{1 21 23}

Monitor liver function tests prior to and during therapy.^{1 21 23}

Development of Other Malignancies

Development of premalignant (e.g., myelodysplastic syndrome, myeloproliferative disorders) and malignant diseases (e.g., acute myelogenous leukemia, bronchial carcinoma) reported;^{1 21 23} association with use of bendamustine has not been established.^{1 21 23}

Local Effects

Extravasation may cause pain, erythema, and marked swelling and may result in hospitalization.^{1 21 23} Monitor infusion site for erythema, swelling, pain, infection, and necrosis during and after administration of bendamustine.^{1 21 23}

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; increased resorptions, skeletal and visceral malformations, and decreased fetal body weights demonstrated in animals.^{1 21 23}

Avoid pregnancy during therapy.^{1 21 23} Perform pregnancy test prior to initiation of therapy.^{1 21 23} Females of reproductive potential should use effective contraceptive methods during and for ≥6 months after discontinuance of therapy.^{1 21 23} If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.^{1 21 23} Advise males with partners of reproductive potential to use a reliable method of contraception during and for ≥3 months after discontinuance of therapy.^{1 21 23}

Specific Populations

Pregnancy

May cause fetal harm.^{1 21 23} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Males of Reproductive Potential

May impair male fertility.^{1 21 23}

Lactation

Not known whether bendamustine is distributed into milk.^{1 21 23} Discontinue nursing during therapy and for ≥1 week after last dose.^{1 21 23}

Pediatric Use

Pharmacokinetic and adverse effect profiles in pediatric patients (1–19 years of age) with relapsed or refractory acute leukemia similar to those in adults.^{1 21 23}

Efficacy not established in pediatric patients.^{1 21 23} Evaluated at a dosage of 90 or 120 mg/m² IV daily on days 1 and 2 of each 21-day cycle in a phase 1–2 study in pediatric patients with relapsed or refractory acute leukemia.^{1 21 23} No responses observed in 32 patients during phase 2; however, complete responses observed in 2 patients with acute lymphocytic leukemia (ALL) during phase 1.^{1 21 23}

Geriatric Use

Pharmacokinetic and adverse effect profiles similar to those in younger adults.^{1 21 23}

Decreased progression-free survival and overall response rate observed in patients ≥65 years of age with CLL compared with younger adults.^{1 23} Overall response rate was 47% in patients ≥65 years of age versus 70% in younger adults.^{1 21 23} Median progression-free survival was 12 months in patients ≥65 years of age versus 19 months in younger adults.^{1 21 23}

Overall response rate and duration of response in patients ≥65 years of age with NHL are similar to results in younger adults.^{1 21 23}

Hepatic Impairment

Pharmacokinetics not substantially altered in patients with total serum bilirubin concentration <1.5 times the ULN and serum AST or ALT concentration <2.5 times the ULN.^{1 21 23}

Pharmacokinetics not evaluated in patients with serum AST or ALT concentration of 2.5–10 times the ULN and total serum bilirubin concentration of 1.5–3 times the ULN or those with total bilirubin concentration >3 times the ULN;^{1 21 23} avoid use in such patients.^{1 21 23}

Renal Impairment

Pharmacokinetics not substantially altered in patients with mild or moderate renal impairment (Cl_cr ≥30 mL/minute).^{1 21 22 23}

Pharmacokinetics not evaluated in patients with severe renal impairment (Cl_cr <30 mL/minute);^{1 21 23} avoid use in such patients.^{1 21 23}

Race

Exposure to bendamustine may be increased in Japanese individuals; however, clinical importance in terms of safety and efficacy has not been established.^{1 21 23}

Gender

Pharmacokinetic and adverse effect profiles not affected substantially by gender.^{1 21 23 25 26}

No clinically important differences in efficacy between men and women observed in patients with rituximab-refractory, indolent B-cell NHL.^{25 26}

Overall response rates in men and women with CLL were 60 and 57%, respectively;^{25 26} median durations of progression-free survival in men and women with CLL were 19 and 13 months, respectively.^{25 26}

Common Adverse Effects

Neutropenia,^{1 4 21 23} thrombocytopenia,^{1 4 5 6 7 21 23} anemia,^{1 4 5 6 21 23} leukopenia,^{1 4 6 7 21 23} pyrexia,^{1 21 23} nausea,^{1 6 21 23} vomiting,^{1 5 6 21 23} lymphopenia,^{1 21 23} elevated bilirubin concentrations,^{1 21 23} fatigue,^{1 21 23} diarrhea,^{1 21 23} constipation,^{1 21 23} decreased weight,^{1 21 23} anorexia, ^{1 21 23} dyspnea,^{1 21 23} cough, ^{1 21 23} headache,^{1 21 23} rash,^{1 21 23} stomatitis.^{1 21 23}

Adverse effects during infusion or within 24 hours post-infusion: Nausea, fatigue.^{1 21 23}

Adverse effects similar following administration as a 10-minute IV infusion (Bendeka) or following IV infusion over 30–60 minutes (Treanda).²¹

Drug Interactions

Metabolized mainly by hydrolysis and, to a lesser extent, by CYP1A2.^{1 21 23}

Does not inhibit CYP isoenzymes 1A2, 2C9, 2C10, 2D6, 2E1, 3A4, or 3A5 or induce CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 3A4, or 3A5 in vitro.^{1 21 23}

Substrate of P-glycoprotein and breast cancer resistance protein (BCRP).^{1 21 23}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP1A2: Potential pharmacokinetic interaction (increased plasma concentrations of bendamustine and increased risk of adverse effects).^{1 21 23} Consider alternative therapy without CYP1A2 inhibition potential.^{1 21 23}

Inducers of CYP1A2: Potential pharmacokinetic interaction (decreased plasma concentrations of bendamustine and potential for reduced efficacy of bendamustine).^{1 21 23} Consider alternative therapy without CYP1A2 induction potential.^{1 21 23}

Bendamustine Pharmacokinetics

Absorption

Bioavailability

Following IV administration, peak plasma concentration attained at the end of the infusion.^{1 21 23}

AUC following 10-minute IV infusion (Bendeka) equivalent to that following 60-minute IV infusion (Treanda); shorter infusion results in higher peak plasma concentrations.²⁵

Plasma Concentrations

Correlation between nausea and peak plasma concentration observed in patients with NHL.^{1 21 23}

Distribution

Extent

Substrate of P-glycoprotein and BCRP.^{1 21 23}

Plasma Protein Binding

94–96%.^{1 21 23}

Elimination

Metabolism

Extensively metabolized by hydrolysis, oxidation, and conjugation.^{1 21 23}

Metabolized mainly via hydrolysis to form metabolites with low cytotoxic activity, monohydroxybendamustine (HP1) and dihydroxybendamustine (HP2), and to a lesser extent via CYP1A2 to form 2 active minor metabolites, γ-hydroxybendamustine (M3) and N-desmethylbendamustine (M4).^{1 21 23}

Elimination Route

Eliminated in urine (approximately 50% [about 3.3% as unchanged drug, <5% as dihydroxy, γ-hydroxy, and N-desmethyl metabolites]) and feces (25%).^{1 21 23}

Half-life

Intermediate half-life of bendamustine is approximately 40 minutes after 60-minute infusion.^{1 21 23} Mean terminal half-lives of γ-hydroxybendamustine and N-desmethylbendamustine are approximately 3 hours and 30 minutes, respectively.^{1 21 23}

Special Populations

Age (31–84 years) does not affect bendamustine pharmacokinetics.^{1 21 23}

In Japanese individuals, exposure to bendamustine may be increased; however, clinical importance not established.^{1 21 23}

Pharmacokinetics not substantially altered in patients with total serum bilirubin concentration <1.5 times the ULN and serum AST or ALT concentration <2.5 times the ULN.^{1 21 23} Combined effect of total serum bilirubin concentration of 1.5–3 times the ULN and serum AST or ALT concentration of 2.5–10 times the ULN or effect of total serum bilirubin concentration >3 times the ULN not established.^{1 21 22 23}

Mild or moderate renal impairment (Cl_cr ≥30 mL/minute) does not substantially alter bendamustine pharmacokinetics.^{1 21 22 23} Effect of severe renal impairment not established.^{1 21 23}

Sex does not substantially affect bendamustine pharmacokinetics.^{1 21 23}

Stability

Storage

Parenteral

Injection Concentrate

Bendeka, Belrapzo: 2–8°C; store partially used vials at 2–8ºC for ≤28 days.²¹ Protect from light.^{21 23} Injection concentrate may partially freeze when refrigerated; allow vials to reach room temperature prior to dilution.^{21 23}

Bendeka: Diluted solutions (in 0.9% sodium chloride or 2.5% dextrose and 0.45% sodium chloride injection) are stable for 24 hours when stored at 2–8°C and for 6 hours when stored at 15–30°C under normal room light conditions.²¹ Diluted solutions (in 5% dextrose injection) are stable for 24 hours when stored at 2–8°C and for 3 hours when stored at 15–30°C under normal room light conditions.²¹

Belrapzo: Diluted solutions (in 0.9% sodium chloride or 2.5% dextrose and 0.45% sodium chloride injection) are stable for 24 hours when stored at 2–8°C and for 3 hours when stored at 15–30°C under normal room light conditions.²³

Powder for Injection

≤25°C; may be exposed to temperatures up to 30°C.¹ Protect from light.¹

Diluted solutions (in 0.9% sodium chloride or 2.5% dextrose and 0.45% sodium chloride injection) are stable for 24 hours when stored at 2–8°C and for 3 hours when stored at 15–30°C under normal room light conditions.¹ Administration must be completed within these time periods.¹

Compatibility

Parenteral

Solution Compatibility (for Belrapzo, Treanda)

Solution Compatibility (for Bendeka)

Actions

• Mechanism(s) of action not conclusively established,^{1 21 23} but may interfere with DNA replication and transcription of RNA, ultimately resulting in disruption of nucleic acid function.^{1 3 8 21 23}

• Cytotoxic activity may also result from induction of p53-dependent genes that activate apoptosis and inhibition of several mitotic checkpoints.^{3 8} As a result, DNA-damaged cells entering the M phase of the cell cycle may undergo mitotic catastrophe, a premature form of necrotic cell death.^{3 8}

• Active against both quiescent and dividing cells.^{1 21 23}

• Cross-resistance between bendamustine and other alkylating agents or fludarabine appears to be incomplete.^{3 5 6 7 8 12}

Advice to Patients

• Risk of allergic reactions; importance of immediately reporting rash, facial swelling, or difficulty breathing during or soon after bendamustine infusion.^{1 21 23}

• Importance of immediately reporting severe or worsening rash or pruritus to clinician.^{1 21 23}

• Risk of leukopenia, thrombocytopenia, and anemia; importance of frequent monitoring of blood cell counts; importance of reporting any shortness of breath, marked fatigue, bleeding, or fever or other manifestations of infection.^{1 21 23}

• Risk of increased fatigue; importance of avoiding driving a vehicle or operating machinery if fatigue occurs.^{1 21 23}

• Risk of nausea, vomiting, and diarrhea; importance of reporting these adverse GI effects so that symptomatic treatment may be provided.^{1 21 23}

• Risk of hepatic toxicity; importance of immediately reporting signs and symptoms of hepatic failure (e.g., jaundice, anorexia, bleeding, bruising).^{1 21 23}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise females of reproductive potential and men with partners of reproductive potential to avoid pregnancy and to use effective contraceptive methods during therapy and for ≥3 months (men with partners of reproductive potential) or ≥6 months (females of reproductive potential) following discontinuance of therapy.^{1 21 23} Importance of advising male patients that bendamustine may impair spermatogenesis.^{1 21 23}

• Importance of advising females to avoid breast-feeding while receiving the drug and for ≥1 week following discontinuance of therapy.^{1 21 23}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{1 21 23}

• Importance of informing patients of other important precautionary information.^{1 21 23} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Frequently asked questions

• Are lung nodules common after Bendeka & Rituxan therapy?
• How is Bendeka different to Treanda?
• Why has Bendeka replaced Treanda?
• How often is Bendeka given and how long does treatment last?
• Does Treanda cause hair loss?
• What is Treanda used for and how does it work?
• What is Bendeka used for?

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