DESCRIPTION
Bendamustine
CLASSIFICATION Alkylating agent
Bifunctional alkylating agent consisting of a purine benzimidazole ring and a nitrogen mustard moiety.
Forms cross-links with DNA resulting in single- and double-strand breaks and inhibition of DNA synthesis and function.
• inhibits mitotic checkpoints and induces mitotic catastrophe, leading to cell death.
Cell cycle–nonspecific. Active in all phases of the cell cycle.
ABSORPTION
High oral bioavailability on the order of 90%. No oral formulation is currently available, and as such, it is administered only via the IV route.
DISTRIBUTION
Bendamustine is highly protein bound (> 95%), mainly to albumin. Protein binding is not affected by age or low serum albumin levels.
INDICATIONS
1. FDA-approved for the treatment of chronic lymphocytic leukemia (CLL).
2. FDA-approved for the treatment of indolent B-cell non-Hodgkin’s lymphoma that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.
DOSAGE RANGE
1. CLL treatment-naïve—100 mg/m2 IV on days 1 and 2 every 28 days. May give up to a total of 6 cycles.
2. Non-Hodgkin’s lymphoma—120 mg/m2 IV on days 1 and 2 every 21 days. May give up to a total of 8 cycles.
DRUG INTERACTIONS
Inhibitors or inducers of CYP1A2—Concurrent use of bendamustine with CYP1A2 inhibitors (ciprofloxacin, fluvoxamine) or CYP1A2 inducers (omeprazole, smoking) may alter bendamustine metabolism and subsequent drug levels.
SPECIAL CONSIDERATIONS
1. Use with caution in patients with mild or moderate renal impairment. Bendamustine should not be used in patients with CrCl < 40 mL/min.
2. Use with caution in patients with mild hepatic impairment. Should not be used in the setting of moderate (SGOT or SGPT 2.5–10 × ULN and total bilirubin 1.5–3 × ULN) or severe (total bilirubin > 3 × ULN) hepatic impairment.
3. Monitor for tumor lysis syndrome, especially within the first treatment cycle. Consider using allopurinol during the first 1 to 2 weeks of bendamustine therapy in patients at high risk.
4. Closely monitor CBCs on a periodic basis. Treatment delays and/or dose reduction may be warranted. Prior to starting the next cycle of therapy, the ANC should be ≥ 1,000/mm3 and the platelet count ≥ 75,000/mm3.
5. Closely monitor for hypersensitivity infusion reactions, and discontinuation of therapy should be considered in patients who experience grade 3 or 4 infusion reactions.
6. Bendamustine therapy should be held or discontinued in the setting of severe or progressive skin reactions.
7. Pregnancy category D. Breastfeeding should be avoided.
TOXICITY 1
Myelosuppression with neutropenia and thrombocytopenia is dose-limiting and may warrant treatment delay or dose reduction.
TOXICITY 2
Mild nausea and vomiting.
TOXICITY 3
Hypersensitivity reactions presenting with fever, chills, pruritus, and rash. Anaphylactoid and severe anaphylactic reactions have occurred rarely.
TOXICITY 4
Pyrexia, fatigue, and asthenia.
TOXICITY 5
Tumor lysis syndrome typically occurs within the first treatment cycle and in high-risk patients.
TOXICITY 6
Skin rash, toxic skin reactions, and bullous exanthema occur in < 10% of patients.
SPECIFICATION
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