Chlorambucil

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Information about Chlorambucil

Chlorambucil is an orally administered alkylating agent which is currently used in the therapy of chronic lymphocytic leukemia, Hodgkin and non-Hodgkin lymphomas, and rarely in severe autoimmune conditions including rheumatoid arthritis, uveitis and nephrotic syndrome.

Liver safety of Chlorambucil

Chlorambucil therapy has been associated with low rates of serum enzyme elevations during therapy and to rare instances of acute, clinically apparent injury.

Mechanism of action of Chlorambucil

Chlorambucil (klor am' bue sil) is an orally available, alkylating agent similar to mechlorethamine, cyclophosphamide and melphalan (nitrogen mustard-like). The alkylating agents act by causing modification and cross linking of DNA, thus inhibiting DNA, RNA and protein synthesis and causing cell death in rapidly dividing cells. alkylating agents also have immunosuppressive activity, and chlorambucil has also been used in the therapy of autoimmune diseases and allograft rejection.

FDA approval information for Chlorambucil

Chlorambucil was approved for use in the United States in 1957. Current major indications include Hodgkin and non-Hodgkin lymphomas, chronic lymphocytic leukemia and lymphosarcoma. Chlorambucil has also been used for macroglobulinemia, polycythemia vera, rheumatoid arthritis, autoimmune uveitis and minimal change nephrotic syndrome, but its link to development of leukemia and secondary cancers has led to recommendations that its use be restricted to malignant conditions. Chlorambucil is available as Leukeran in tablets of 2 mg, and the usual dose ranges from 2 to 10 mg daily, often being given long term. Chlorambucil is generally well tolerated, and flexible dosing allows for dose adjustment to minimize side effects.

Side effects of Chlorambucil

Chlorambucil shares common side effects with other alkylating agents such as nausea, vomiting, diarrhea, alopecia, oral ulcers, bone marrow suppression, hypersensitivity reactions and rash. Long term therapy may be associated with an increased rate of acute myelocytic leukemia, interstitial pneumonitis and pulmonary fibrosis. Acute hypersensitivity reactions are rare but can include drug fever, angioedema, erythema multiforme, and Stevens Johnson syndrome.

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