Bendamustine

Bendamustine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

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Overview

Bendamustine is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin Lymphoma (NHL). Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Chronic Lymphocytic Leukemia

• Dosing information

• Recommended Dosage:
• Recommended dosage:100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles.

• Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL:

• TREANDA administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant ≥ 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 109/L, platelets ≥ 75 x 109/L], TREANDA can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted.

• Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle.
• Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle.
• Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Bendamustine in adult patients.

Non–Guideline-Supported Use

Metastatic breast cancer

• Dosing information

• ‘120 mg/m(2) IV over 30 minutes on days 1 and 2 every 4 weeks'17872900
• 60 mg/m(2) IV over 30 minutes on days 1, 8, and 15 every 28 days17667603

Multiple myeloma

• Dosing information

• 150 mg/m(2) (in 500 mL of normal saline) IV over 30 minutes on days 1 and 216402269

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

The effectiveness of TREANDA in pediatric patients has not been established

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Bendamustine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Bendamustine in pediatric patients.

Contraindications

TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine.

Warnings

Myelosuppression

TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies (see Table 4). Three patients (2%) died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV). In the event of treatment-related myelosuppression, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the ANC should be ≥ 1 x 109/L and the platelet count should be ≥ 75 x 109/L. [See Dosage and Administration (2.1) and (2.2)]

Infections

Infection, including pneumonia, sepsis, septic shock, and death have occurred in adult and pediatric patients in clinical trials and in postmarketing reports. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Advise patients with myelosuppression following TREANDA treatment to contact a physician if they have symptoms or signs of infection.

Anaphylaxis and Infusion Reactions

Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experience Grade 3 or worse allergic-type reactions should not be rechallenged. Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions. Discontinue TREANDA for patients with Grade 4 infusion reactions. Consider discontinuation for Grade 3 infusions reactions as clinically appropriate considering individual benefits, risks, and supportive care.

Tumor Lysis Syndrome

Tumor lysis syndrome associated with TREANDA treatment has occurred in patients in clinical trials and in postmarketing reports. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. Allopurinol has also been used during the beginning of TREANDA therapy. However, there may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly [see Warnings and Precautions (5.5)].

Skin Reactions

Skin reactions have been reported with TREANDA treatment in clinical trials and postmarketing safety reports, including rash, toxic skin reactions and bullous exanthema. Some events occurred when TREANDA was given in combination with other anticancer agents. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab (see rituximab package insert). Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. The relationship to TREANDA cannot be determined. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA.

Other Malignancies

There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with TREANDA therapy has not been determined.

Extravasation Injury

TREANDA extravasations have been reported in post marketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA.

Embryo-fetal Toxicity

TREANDA can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights.

Adverse Reactions

Clinical Trials Experience

The data described below reflect exposure to TREANDA in 153 patients with CLL studied in an active-controlled, randomized trial. The population was 45-77 years of age, 63% male, 100% white, and were treatment naïve. All patients started the study at a dose of 100 mg/m2 intravenously over 30 minutes on Days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0. Non-hematologic adverse reactions (any grade) in the TREANDA group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis. Worsening hypertension was reported in 4 patients treated with TREANDA in the CLL trial and in none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving TREANDA were hypersensitivity (2%) and pyrexia (1%). Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study.

Postmarketing Experience

There is limited information regarding Bendamustine Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Bendamustine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Bendamustine in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Bendamustine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Bendamustine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Bendamustine in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Bendamustine in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Bendamustine in geriatric settings.

Gender

There is no FDA guidance on the use of Bendamustine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Bendamustine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Bendamustine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Bendamustine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Bendamustine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Bendamustine in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Bendamustine Administration in the drug label.

Monitoring

There is limited information regarding Bendamustine Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Bendamustine and IV administrations.

Overdosage

There is limited information regarding Bendamustine overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Bendamustine Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Bendamustine Mechanism of Action in the drug label.

Structure

There is limited information regarding Bendamustine Structure in the drug label.

Pharmacodynamics

There is limited information regarding Bendamustine Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Bendamustine Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Bendamustine Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Bendamustine Clinical Studies in the drug label.

How Supplied

There is limited information regarding Bendamustine How Supplied in the drug label.

Storage

There is limited information regarding Bendamustine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Bendamustine Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Bendamustine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Bendamustine Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Bendamustine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.