Bendamustine

• Approved Indications:
• Treatment of chronic lymphocytic leukemia (CLL) in adults.
• Treatment of indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
• Treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy.
• Off-label Uses:
• Certain aggressive lymphomas refractory to standard therapy.
• Other hematologic malignancies as determined by oncologists in clinical practice.

• Route: Intravenous infusion.
• Adult Dosing:
• CLL: 100 mg/m² IV on Days 1 and 2 of a 28-day cycle.
• Indolent NHL and MCL: 120 mg/m² IV on Days 1 and 2 of a 21-day cycle.
• Treatment usually continued for 6 cycles or until disease progression or unacceptable toxicity.
• Pediatrics: Safety and efficacy not established; use only in clinical trials or specialized centers.
• Elderly: Dose adjustments may be required based on tolerability and renal/hepatic function.
• Special Populations:
• Renal impairment: Use with caution; no specific dose adjustment but monitor closely.
• Hepatic impairment: Use cautiously; severe impairment not studied.
• Administration Notes:
• Infuse over 30-60 minutes diluted in appropriate IV fluids.
• Pre-medications may be administered to prevent nausea and hypersensitivity reactions.

Bendamustine is an alkylating agent with a unique mechanism combining properties of alkylators and purine analogs. It causes cross-linking of DNA strands via alkylation, leading to disruption of DNA replication and transcription. This results in DNA damage triggering apoptosis and cell death in rapidly dividing malignant cells, particularly lymphoid cells. Its dual mechanism may overcome resistance to other alkylating agents.

• Absorption: Administered IV; 100% bioavailability.
• Distribution: Widely distributed; plasma protein binding approximately 95%.
• Metabolism: Primarily metabolized in the liver via hydrolysis and CYP1A2 to active metabolites.
• Elimination: Metabolites and unchanged drug excreted via urine and feces.
• Half-life: Biphasic; initial half-life approximately 40 minutes; terminal half-life 3–4 hours.

• Pregnancy: Category D — positive evidence of human fetal risk. Use only if potential benefits justify risks. Avoid pregnancy during treatment.
• Lactation: Unknown if excreted in human milk; breastfeeding not recommended during treatment.

• Primary Therapeutic Class: Antineoplastic Agent
• Subclass: Alkylating Agent (Nitrogen Mustard Derivative)

• Known hypersensitivity to bendamustine or any formulation components.
• Severe bone marrow suppression.
• Active severe infections.

• Bone marrow suppression: Monitor blood counts; risk of neutropenia, thrombocytopenia, anemia.
• Increased risk of infections due to immunosuppression.
• Infusion-related reactions: Monitor for fever, chills, rash.
• Hepatic and renal function impairment requires close monitoring.
• Secondary malignancies and tumor lysis syndrome reported.
• Use caution in elderly patients and those with comorbidities.

• Common:
• Hematologic: Neutropenia, thrombocytopenia, anemia.
• Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis.
• Fatigue, pyrexia, headache.
• Skin reactions: rash, pruritus.
• Serious/Rare:
• Severe infections, sepsis.
• Tumor lysis syndrome.
• Hypersensitivity/anaphylaxis.
• Secondary malignancies.

• Avoid co-administration with other myelosuppressive agents without close monitoring.
• CYP1A2 inhibitors/inducers may alter bendamustine metabolism (e.g., fluvoxamine, ciprofloxacin).
• No significant CYP3A4 interactions.

• Guidelines endorse bendamustine as first-line or salvage therapy in CLL and indolent NHL.
• Recent data support combination regimens to improve outcomes.
• Ongoing monitoring for long-term safety advised.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light.
• Use reconstituted solution promptly; do not freeze.
• Handle with caution using appropriate protective equipment.