Chlorambucil

• Chronic Lymphocytic Leukemia (CLL):
  Used as a first-line or palliative treatment to reduce lymphocyte count and control disease progression.
• Hodgkin’s Disease and Non-Hodgkin’s Lymphoma:
  Employed for certain lymphomas responsive to alkylating agents.
• Waldenström’s Macroglobulinemia:
  Treatment of malignant lymphoproliferative disorders.
• Other Hematologic Malignancies:
  Used in some cases of multiple myeloma and other leukemias as part of combination chemotherapy or palliative care.
• Off-label Uses:
  Occasionally used in autoimmune disorders like rheumatoid arthritis and nephrotic syndrome when resistant to other treatments.

• Route: Oral administration.
• Adults (Hematologic Malignancies):
  Initial dose typically 0.1 to 0.2 mg/kg/day orally in divided doses for 4 to 6 weeks, or 10 to 20 mg daily.
  Maintenance or repeated courses as tolerated and based on clinical response.
• Elderly:
  Start with lower doses and adjust carefully due to increased risk of myelosuppression.
• Pediatrics:
  Limited data; doses adjusted by body surface area and clinical response.
• Renal/Hepatic Impairment:
  Use with caution; no specific dosing guidelines but monitor closely for toxicity.
• Duration:
  Treatment duration varies based on disease and response; intermittent or continuous dosing.

Chlorambucil is a bifunctional alkylating agent belonging to the nitrogen mustard class. It forms reactive alkyl groups that bind covalently to nucleophilic sites on DNA, particularly at the N7 position of guanine bases, leading to DNA cross-linking. This cross-linking inhibits DNA replication and RNA transcription, ultimately triggering apoptosis in rapidly dividing cells such as malignant lymphocytes. The drug’s cytotoxicity disrupts cell proliferation and induces cell death, making it effective in treating certain cancers.

• Absorption:
  Well absorbed orally, with peak plasma levels occurring within 1 to 2 hours.
• Distribution:
  Widely distributed throughout body tissues; crosses the placenta and is found in breast milk.
• Metabolism:
  Metabolized primarily in the liver to active phenylacetic acid mustard metabolite.
• Elimination:
  Excreted mainly via the kidneys as metabolites; minor amount excreted unchanged in urine.
• Half-life:
  Approximately 1.5 hours for parent drug; active metabolites have longer half-life.

• Pregnancy:
  Category D — Positive evidence of human fetal risk based on adverse reaction data; contraindicated in pregnancy unless benefits outweigh risks.
• Lactation:
  Excreted in breast milk; breastfeeding not recommended during treatment due to potential toxicity.

• Alkylating agent
• Antineoplastic agent

• Known hypersensitivity to chlorambucil or related alkylating agents.
• Severe bone marrow suppression.
• Active infections requiring systemic therapy.
• Pregnancy and breastfeeding.

• Monitor blood counts regularly due to risk of myelosuppression (leukopenia, thrombocytopenia, anemia).
• Risk of secondary malignancies including leukemia and bladder cancer.
• Use caution in patients with hepatic or renal impairment.
• Potential for infertility; counsel patients accordingly.
• Avoid live vaccines during therapy.
• Increased risk of infections; monitor closely.

Common:

• Myelosuppression (neutropenia, thrombocytopenia)
• Nausea, vomiting
• Anorexia
• Fatigue
• Mild alopecia
• Diarrhea

Serious/Rare:

• Severe bone marrow suppression
• Secondary malignancies (leukemia, bladder cancer)
• Hepatotoxicity
• Allergic reactions
• Pulmonary toxicity (rare)

• Additive myelosuppression with other bone marrow suppressive agents.
• Increased toxicity with allopurinol due to altered metabolism.
• Potential reduced efficacy with drugs inducing hepatic enzymes.
• Avoid concurrent live vaccines.

• Current guidelines recommend careful monitoring of blood counts and liver function during therapy.
• Emphasis on patient counseling regarding long-term risks including secondary cancers.
• Newer combination regimens with targeted agents may reduce reliance on chlorambucil in some malignancies.

• Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.