INN monograph
Bendamustine
Therapeutic agent (verify pharmacological class) · POM
Source-linked · Updated 03 Aug 2026 · Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Kenya market
Wholesale / list prices where loaded
Risk first
Contraindications
- (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, absolute ethanol, sodium hydroxide and monothioglycerol. [see Warnings and Precautions ( 5.4 )] Bendamustine hydrochloride injection is contraindicated in patients with a history of a hypersensitivity reaction to bendamustine, polyethylene glycol 400, absolute ethanol, sodium hydroxide and monothioglycerol.
- Reactions to bendamustine hydrochloride have included anaphylaxis and anaphylactoid reactions.
- ( 4 , 5.4 )
Precautions
- 5 WARNINGS AND PRECAUTIONS Myelosuppression: Delay or reduce dose and restart treatment based on ANC and platelet count recovery.
- ( 5.1 ) Infections: Monitor for fever and other signs of infection or reactivation of infections and treat promptly.
- ( 5.2 ) Progressive multifocal leukoencephalopathy (PML): Monitor for new or worsening neurological, cognitive or behavioral signs or symptoms suggestive of PML.
- ( 5.3 ) Anaphylaxis and Infusion Reactions: Severe anaphylactic reactions have occurred.
- Monitor clinically and discontinue drug for severe reactions.
- Pre-medicate in subsequent cycles for milder reactions.
- ( 5.4 ) Tumor Lysis Syndrome: May lead to acute renal failure and death
- anticipate and use supportive measures in patients at high risk.
- ( 5.5 ) Skin Reactions: Discontinue for severe skin reactions.
- Cases of SJS, DRESS and TEN, some fatal, have been reported.
- ( 5.6 ) Hepatotoxicity: Monitor liver chemistry tests prior to and during treatment.
- ( 5.7 ) Other Malignancies: Pre-malignant and malignant diseases have been reported.
Point of care
Dosing
Adult
: • 120 mg/m 2 infused intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles ( 2.1 ) 2.1 Dosing Instructions for NHL Recommended Dosage: The recommended dosage is 120 mg/m 2 administered intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Dose Delays, Dosage Modifications and Reinitiation of Therapy for NHL: Delay bendamustine hydrochloride injection administration in the event of a Grade 4 hematologic toxicity or clinically significant greater or equal to Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 10 9 /L, platelets ≥ 75 x 10 9 /L], reinitiate bendamustine hydrochloride injection at the discretion of the treating physician. In addition, consider dose reduction. [ see Warnings and Precautions ( 5.1 )] Dosage modifications for hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m 2 on Days 1 and 2 of each cycle; if Grade 4 toxicity recurs, reduce the dose to 60 mg/m 2 on Days 1 and 2 of each cycle. Dosage modifications for non-hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m 2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m 2 on Days 1 and 2 of each cycle. 2.2 Preparation for Intravenous Administration Bendamustine hydrochloride injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Bendamustine hydrochloride injection is in a multiple-dose vial. Bendamustine hydrochloride injection is a clear and colorless to yellow solution. Store bendamustine hydrochloride injection at recommended refrigerated storage conditions (2°C to 8°C or 36°F to 46°F). When refrigerated the contents may freeze. Allow the vial to reach room temperature (15°C to 30°C or 59°F to 86°F) prior to use. Observe the contents of the vial for any visible solid or particulate matter and discoloration. Do not use the product if solid or particulate matter is observed after reaching room temperature. Intravenous Infusion Aseptically withdraw the volume needed for the required dose from the 25 mg/mL solution as per Table A below and immediately transfer to a 500 mL infusion bag of one of the following diluents: - 0.9% Sodium Chloride Injection, USP; or - 2.5% Dextrose/0.45% Sodium Chloride Injection, USP. The resulting final concentration of bendamustine hydrochloride injection in the infusion bag should be within 0.05 mg/mL to 0.7 mg/mL. After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear and colorless to slightly yellow solution. Use either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, for dilution, as outlined above. No other diluents have been shown to be compatible. Table A: Volume (mL) of Bendamustine Hydrochloride Injection required for dilution into 500 mL of 0.9% Sodium Chloride Injection, USP, or 0.45% Sodium Chloride/2.5% Dextrose Injection, USP for a given dose (mg/m 2 ) and Body Surface Area (m 2 ) Body Surface Area (m 2 ) Volume of Bendamustine Hydrochloride Injection to withdraw (mL) 120 mg/m 2 90 mg/m 2 60 mg/m 2 1 4.8 3.6 2.4 1.1 5.3 4 2.6 1.2 5.8 4.3 2.9 1.3 6.2 4.7 3.1 1.4 6.7 5 3.4 1.5 7.2 5.4 3.6 1.6 7.7 5.8 3.8 1.7 8.2 6.1 4.1 1.8 8.6 6.5 4.3 1.9 9.1 6.8 4.6 2 9.6 7.2 4.8 2.1 10.1 7.6 5 2.2 10.6 7.9 5.3 2.3 11 8.3 5.5 2.4 11.5 8.6 5.8 2.5 12 9 6 2.6 12.5 9.4 6.2 2.7 13 9.7 6.5 2.8 13.4 10.1 6.7 2.9 13.9 10.4 7 3 14.4 10.8 7.2 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics. 2.3 Admixture Stability Bendamustine hydrochloride injection contains no antimicrobial preservative. The admixture should be prepared as close as possible to the time of patient administration. If diluted with 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored refrigerated (2°C to 8°C or 36°F to 46°F) or for 3 hours when stored at room temperature (15°C to 30°C or 59°F to 86°F) and room light. Administration of diluted bendamustine hydrochloride injection must be completed within this period of time. Bendamustine hydrochloride injection is supplied in a multiple-dose vial. Retain the partially used vial in original package to protect from light and store refrigerated (2°C to 8°C or 36°F to 46°F) if additional dose withdrawal from the same vial is intended. 2.4 Stability of Partially Used Vials (Needle Punched Vials) Bendamustine hydrochloride injection is supplied as a multiple-dose vial. Although it does not contain any antimicrobial preservative, bendamustine hydrochloride injection is bacteriostatic. The partially used vials are stable for up to 28 days when stored in its original carton under refrigeration (2°C to 8°C or 36°F to 46°F). Each vial is not recommended for more than a total of six (6) dose withdrawals. After first use, store the partially used vial in original carton at 2°C to 8°C (36°F to 46°F), and then discard after 28 days.
Paediatric
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Safety, pharmacokinetics and efficacy were assessed in a single open-label trial (NCT01088984) in patients aged 1 to 19 years with relapsed or refractory acute leukemia, including 27 patients with acute lymphocytic leukemia (ALL) and 16 patients with acute myeloid leukemia (AML). Bendamustine hydrochloride was administered as an intravenous infusion over 60 minutes on Days 1 and 2 of each 21-day cycle. There was no treatment response (CR+ CRp) in any patient. The safety profile in these patients was consistent with that seen in adults, and no new safety signals were identified. The pharmacokinetics of bendamustine in 43 patients, aged 1 to 19 years (median age of 10 years) were within range of values previously observed in adults given the same dose based on body surface area.
Renal
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Safety
Drug interactions
- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Safety
Adverse effects
- information.
- Myelosuppression [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions ( 5.3 )] Anaphylaxis and Infusion Reactions [see Warnings and Precautions ( 5.4 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )] Skin Reactions [see Warnings and Precautions ( 5.6 )] Hepatotoxicity [see Warnings and Precautions ( 5.7 )] Other Malignancies [see Warnings and Precautions ( 5.8 )] Extravasation Injury [ see Warnings and Precautions ( 5.9 ) ] Adverse reactions (frequency >5%) during infusion and within 24 hours post-infusion are nausea and fatigue.
- ( 6.1 ) Most common adverse reactions (≥15%) for NHL are lymphopenia, leukopenia, anemia, neutropenia, thrombocytopenia, nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.( 6.1 ).
- To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Clinical Trials Experience in NHL The data described below reflect exposure to bendamustine hydrochloride in 176 patients with indolent B-cell NHL treated in two single-arm studies.
- The population was 31 to 84 years of age, 60% male, and 40% female.
- The race distribution was 89% White, 7% Black, 3% Hispanic, 1% other, and <1% Asian.
- These patients received bendamustine hydrochloride at a dose of 120 mg/m 2 intravenously on Days 1 and 2 for up to eight 21-day cycles.
- The adverse reactions occurring in at least 5% of the NHL patients, regardless of severity, are shown in Table 3.
- The most common non-hematologic adverse reactions (≥30%) were nausea (75%), fatigue (57%), vomiting (40%), diarrhea (37%) and pyrexia (34%).
- The most common non-hematologic Grade 3 or 4 adverse reactions (≥5%) were fatigue (11%), febrile neutropenia (6%), and pneumonia, hypokalemia and dehydration, each reported in 5% of patients.
- Table 3: Non-Hematologic Adverse Reactions Occurring in at Least 5% of NHL Patients Treated with Bendamustine Hydrochloride by System Organ Class and Preferred Term (N=176) Body System Number (%) of patients* Adverse Reaction All Grades Grade 3/4 Total number of patients with at least 1 adverse reaction 176 (100) 94 (53) Cardiac disorders Tachycardia 13 (7) 0 Gastrointestinal disorders Nausea 132 (75) 7 (4) Vomiting 71 (40) 5 (3) Diarrhea 65 (37) 6 (3) Constipation 51 (29) 1 (<1) Stomatitis 27 (15) 1 (<1) Abdominal pain 22 (13) 2 (1) Dyspepsia 20 (11) 0 Gastroesophageal reflux disease 18 (10) 0 Dry mouth 15 (9) 1 (<1) Abdominal pain upper 8 (5) 0 Abdominal distension 8 (5) 0 General disorders and administration site conditions Fatigue 101 (57) 19 (11) Pyrexia 59 (34) 3 (2) Chills 24 (14) 0 Edema peripheral 23 (13) 1 (<1) Asthenia 19 (11) 4 (2) Chest pain 11 (6) 1 (<1) Infusion site pain 11 (6) 0 Pain 10 (6) 0 Catheter site pain 8 (5) 0 Infections and infestations Herpes zoster 18 (10) 5 (3) Upper respiratory tract infection 18 (10) 0 Urinary tract infection 17 (10) 4 (2) Sinusitis 15 (9) 0 Pneumonia 14 (8) 9 (5) Febrile neutropenia 11 (6) 11 (6) Oral candidiasis 11 (6) 2 (1) Nasopharyngitis 11 (6) 0 Investigations Weight decreased 31 (18) 3 (2) Metabolism and nutrition disorders Anorexia 40 (23) 3 (2) Dehydration 24 (14) 8 (5) Decreased appetite 22 (13) 1 (<1) Hypokalemia 15 (9) 9 (5) Musculoskeletal and connective tissue disorders Back pain 25 (14) 5 (3) Arthralgia 11 (6) 0 Pain in extremity 8 (5) 2 (1) Bone pain 8 (5) 0 Nervous system disorders Headache 36 (21) 0 Dizziness 25 (14) 0 Dysgeusia 13 (7) 0 Psychiatric disorder s Insomnia 23 (13) 0 Anxiety 14 (8) 1 (<1) Depression 10 (6) 0 Respiratory, thoracic and mediastinal disorders Cough 38 (22) 1 (<1) Dyspnea 28 (16) 3 (2) Pharyngolaryngeal pain 14 (8) 1 (<1) Wheezing 8 (5) 0 Nasal congestion 8 (5) 0 Skin and subcutaneous tissue disorders Rash 28 (16) 1 (<1) Pruritus 11 (6) 0 Dry skin 9 (5) 0 Night sweats 9 (5) 0 Hyperhidrosis 8 (5) 0 Vascular disorders Hypotension 10 (6) 2 (1) *Patients may have reported more than 1 adverse reaction.
- NOTE: Patients counted only once in each preferred term category and once in each system organ class category.
- Hematologic toxicities, based on laboratory values and CTC grade, in NHL patients treated in both single arm studies combined are described in Table 4.
Use
Indications
- (NHL) Bendamustine hydrochloride injection is indicated for the treatment of adult patients with indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
- Bendamustine hydrochloride injection is an alkylating drug indicated for treatment of adult patients with: • Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
Pharmacology
Mode of action
ring.
Full mechanism text
ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown.
ADME
Pharmacokinetics & PD
| Onset | Product-specific |
|---|---|
| Duration | Product-specific |
| Route | INTRAVENOUS |
| Absorption | Following a single IV dose of bendamustine hydrochloride C max typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied. |
| Distribution | The protein binding of bendamustine ranged from 94% to 96% and was concentration independent from 1 to 50 mcg/mL. The blood to plasma concentration ratios in human blood ranged from 0.84 to 0.86 over a concentration range of 10 to 100 mcg/mL. The mean steady-state volume of distr... |
| Metabolism | Bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways. Bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity in vitro . Two active minor metabolites,... |
| Elimination | After a single intravenous dose of 120 mg/m 2 of bendamustine over 1 hour, the intermediate |
| Half-life | (t ½ ) of the parent compound is approximately 40 minutes. The mean terminal |
Full PK/PD text
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown. 12.2 Pharmacodynamics Based on the pharmacokinetics/pharmacodynamics analyses of data from adult NHL patients, nausea increased with increasing bendamustine C max . Cardiac Electrophysiology The effect of bendamustine on the QTc interval was evaluated in 53 patients with indolent NHL and mantle cell lymphoma on Day 1 of Cycle 1 after administration of rituximab at 375 mg/m 2 intravenous infusion followed by a 30-minute intravenous infusion of bendamustine at 90 mg/m 2 /day. No mean changes greater than 20 milliseconds were detected up to one hour post infusion. The potential for delayed effects on the QT interval after one hour was not evaluated. 12.3 Pharmacokinetics Absorption Following a single IV dose of bendamustine hydrochloride C max typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied. Distribution The protein binding of bendamustine ranged from 94% to 96% and was concentration independent from 1 to 50 mcg/mL. The blood to plasma concentration ratios in human blood ranged from 0.84 to 0.86 over a concentration range of 10 to 100 mcg/mL. The mean steady-state volume of distribution (V ss ) of bendamustine was approximately 20 to 25 L. Elimination After a single intravenous dose of 120 mg/m 2 of bendamustine over 1 hour, the intermediate half-life (t ½ ) of the parent compound is approximately 40 minutes. The mean terminal elimination t ½ of two active metabolites, γ-hydroxybendamustine (M3) and N-desmethylbendamustine (M4) are approximately 3 hours and 30 minutes, respectively. Bendamustine clearance in humans is approximately 700 mL/min. Metabolism Bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways. Bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity in vitro . Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2 in vitro . M3 and M4 concentrations of these metabolites in plasma are 1/10 th and 1/100 th that of the parent compound, respectively. Excretion Following IV infusion of radiolabeled bendamustine hydrochloride in cancer patients, approximately 76% of the dose was recovered. Approximately 50% of the dose was recovered in the urine (3.3% unchanged) and approximately 25% of the dose was recovered in the feces. Less than 1% of the dose was recovered in the urine as M3 and M4, and less than 5% of the dose was recovered in the urine as HP2. Specific Populations No clinically meaningful effects on the pharmacokinetics of bendamustine were observed based on age (31 to 84 years), sex, mild to moderate renal impairment (CLcr ≥ 30 mL/min), or hepatic impairment with total bilirubin 1.5 < ULN and AST or ALT < 2.5 × ULN. The effects of severe renal impairment (CLcr < 30 mL/min), or hepatic impairment with total bilirubin 1.5-3 × ULN and AST or ALT 2.5-10 × ULN or total bilirubin > 3 × ULN on the pharmacokinetics of bendamustine is unknown. Race/Ethnicity Exposures in Japanese subjects (n=6) were 40% higher than that in non-Japanese subjects receiving the same dose. The clinical importance of this difference on the safety and efficacy of bendamustine hydrochloride in Japanese subjects has not been established. Drug Interaction Studies In Vitro Studies Effect of Bendamustine on CYP Substrates Bendamustine did not inhibit CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5. Bendamustine did not induce metabolism of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Effect of Transporters on Bendamustine Hydrochloride Bendamustine is a substrate of P-glycoprotein and breast cancer resistance protein (BCRP).
Kenya
Brands & prices
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Special populations
Pregnancy & lactation
Pregnancy
8.1 Pregnancy Risk Summary In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data). There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m 2 (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated. Repeat intraperitoneal administration of bendamustine hydrochloride in mice on gestation days 7 to 11 resulted in an increase in resorptions from 75 mg/m 2 (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m 2 (approximately 0.9 times the MRHD), similar to those seen after a single intraperitoneal administration. Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m 2 (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses. A significant increase in external (effect on tail, head, and herniation of external organs [exomphalos]) and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats.
Lactation
Lactation: Advise not to breastfeed. ( 8.2 ) Infertility: May impair fertility. ( 8.3 ) Renal Impairment: Do not use in patients with creatinine clearance <30 mL/min. ( 8.6 ) Hepatic Impairment: Do not use in patients with total bilirubin 1.5-3 x ULN and AST or ALT 2.5-10 x ULN, or total bilirubin >3 x ULN. ( 8.7 ) 8.1 Pregnancy Risk Summary In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data). There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m 2 (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated. Repeat intraperitoneal administration of bendamustine hydrochloride in mice on gestation days 7 to 11 resulted in an increase in resorptions from 75 mg/m 2 (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m 2 (approximately 0.9 times the MRHD), similar to those seen after a single intraperitoneal administration. Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m 2 (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses. A significant increase in external (effect on tail, head, and herniation of external organs [exomphalos]) and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats. 8.2 Lactation Risk Summary There are no data on the presence of bendamustine hydrochloride or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with bendamustine hydrochloride injection, and for 1 week after the last dose. 8.3 Females and Males of Reproductive Potential Bendamustine hydrochloride injection can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )]. Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiation of treatment with bendamustine hydrochloride injection. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with bendamustine hydrochloride injection and for 6 months after the last dose. Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with bendamustine hydrochloride injection and for 3 months after the last dose [see Nonclinical Toxicology ( 13.1 )]. Infertility Based on findings from clinical studies, bendamustine hydrochloride injection may impair male fertility. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs. In some instances, spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued. Advise patients of the potential risk to their reproductive capacities. Based on findings from animal studies, bendamustine hydrochloride injection may impair male fertility due to an increase in morphologically abnormal spermatozoa. The long-term effects of bendamustine hydrochloride injection on male fertility, including the reversibility of adverse effects, have not been studied [see Nonclinical Toxicology ( 13.1 )]. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Safety, pharmacokinetics and efficacy were assessed in a single open-label trial (NCT01088984) in patients aged 1 to 19 years with relapsed or refractory acute leukemia, including 27 patients with acute lymphocytic leukemia (ALL) and 16 patients with acute myeloid leukemia (AML). Bendamustine hydrochloride was administered as an intravenous infusion over 60 minutes on Days 1 and 2 of each 21-day cycle. There was no treatment response (CR+ CRp) in any patient. The safety profile in these patients was consistent with that seen in adults, and no new safety signals were identified. The pharmacokinetics of bendamustine in 43 patients, aged 1 to 19 years (median age of 10 years) were within range of values previously observed in adults given the same dose based on body surface area. 8.5 Geriatric Use No overall differences in safety were observed between patients ≥65 years of age and younger patients. No overall differences in efficacy in patients with non-Hodgkin Lymphoma were observed between geriatric patients and younger patients. 8.6 Renal Impairment Do not use bendamustine hydrochloride injection in patients with creatinine clearance (CLcr) < 30 mL/min. [see Clinical Pharmacology ( 12.3 )] 8.7 Hepatic Impairment Do not use bendamustine hydrochloride injection in patients with AST or ALT 2.5 to 10 × upper limit of normal (ULN) and total bilirubin 1.5 to 3 × ULN, or total bilirubin > 3 × ULN [see Clinical Pharmacology (12.3 )]
Diet
Food & alcohol
- Drug & food interactions (label) 7 DRUG INTERACTIONS Consider alternative therapies that are not CYP1A2 inducers or inhibitors during treatment with bendamustine hydrochloride injection. ( 7.1 ) 7.1 Effect of Other Drugs on Bendamustine Hydrochloride Injection CYP1A2 Inhibitors The coadministration of bendamustine hydrochloride injection with CYP1A2 inhibitors may increase bendamustine plasma concentrations and may result in increased incidence of adverse reactions with bendamustine hydrochloride injection [see Clinical Pharmacology ( 12.3 )]. Consider alternative therapies that are not CYP1A2 inhibitors during treatment with bendamustine hydrochloride injection. CYP1A2 Inducers The coadministration of bendamustine hydrochloride injection with CYP1A2 inducers may decrease bendamustine plasma concentrations and may result in decreased efficacy of bendamustine hydrochloride injection [see Clinical Pharmacology ( 12.3 )]. Consider alternative therapies that are not CYP1A2 inducers during treatment with bendamustine hydrochloride injection.
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Sources & disclaimer
Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Clinical review date not recorded.
Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.