Generic Name

Chlorambucil

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Classification

FDA Approved Indications

• Chronic lymphocytic leukemia (CLL)
• Hodgkin's lymphoma (occasionally)
• Other lymphoid malignancies

Mechanism of Action

Chlorambucil crosslinks DNA strands, leading to apoptosis of rapidly dividing cells. It alkylates RNA and DNA, disrupting nucleic acid synthesis and function.

Dosage and Administration

Adult: Typically 0.1-0.2 mg/kg/day orally, divided into doses, with adjustments based on response and tolerability.

Pediatric: Use is limited; doses are calculated based on body surface area or weight, under specialist supervision.

Geriatric: Start at lower doses due to increased sensitivity and potential for adverse effects.

Renal Impairment: Use with caution; monitor renal function and adjust dose if necessary.

Hepatic Impairment: Use cautiously; consider dose adjustments and close monitoring.

Pharmacokinetics

Absorption: Well absorbed after oral administration

Distribution: Widely distributed in body tissues, crosses the blood-brain barrier

Metabolism: Metabolized in the liver, forms active metabolites

Excretion: Primarily excreted in urine

Half Life: Approximately 1.5 hours, though active metabolites may last longer

Contraindications

• Hypersensitivity to chlorambucil or other alkylating agents.
• Pregnancy and lactation (see detailed precautions)

Precautions

• Use cautiously in patients with bone marrow suppression, hepatic or renal impairment, active infections, or history of secondary malignancies. Monitor blood counts regularly. Pregnant women should avoid use; effective contraception is advised during treatment.

Adverse Reactions - Common

• Bone marrow suppression (anemia, leukopenia, thrombocytopenia) (Common)
• Alopecia (Common)
• Nausea and vomiting (Common)

Adverse Reactions - Serious

• Secondary malignancies, such as leukemia (Rare)
• Severe immunosuppression leading to infection (Rare)
• Gastrointestinal ulceration (Rare)

Drug-Drug Interactions

• Other myelosuppressive agents, including chemotherapies and immunosuppressants.
• CNS depressants.

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report signs of infection, unusual bleeding, or fatigue.
• Avoid live vaccines during therapy.
• Use contraception during and for at least 6 months after treatment.

Special Considerations

Black Box Warnings:

• Risk of secondary malignancies, including leukemia and other solid tumors.

Genetic Factors: N/A

Lab Test Interference: N/A

Overdose Management

Signs/Symptoms: Severe myelosuppression, infection, bleeding, gastrointestinal toxicity.

Treatment: Supportive care; management of cytopenias; consider hemofiltration or exchange transfusion in severe cases; use of rescue agents not well established.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable under recommended storage conditions for the shelf life specified by manufacturer.