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Chlorambucil (Leukeran)
(klor- AM-byou-sill)
Pregnancy Category: D Leukeran (Abbreviation: CHL) (Rx)

Classification: Antineoplastic, alkylating agent

See Also: See also Antineoplastic Agents and Alkylating Agents .

Action/Kinetics: Cell-cycle nonspecific; cytotoxic to nonproliferating cells and has immunosuppressant activity. Forms an unstable ethylenimmonium ion which binds (alkylates) with intracellular substances such as nucleic acids. The cytotoxic effect is due to cross-linking of strands of DNA and RNA and inhibition of protein synthesis. Rapidly absorbed from the GI tract. Peak plasma levels: 1 hr. t½, plasma;: 1.5 hr. 99% bound to plasma proteins, especially albumin. Extensively metabolized by the liver; at least one metabolite is active. Fifteen to 60% is excreted through the urine 24 hr after drug administration; 40% is bound to tissues, including fat.

Uses: Palliation in chronic lymphocytic leukemia, malignant lymphomas (including lymphosarcoma), giant follicular lymphomas, and Hodgkin's disease. Investigational: Uveitis and meningoencephalitis associated with Behcet's disease. With a corticosteroid for idiopathic membranous nephropathy. Rheumatoid arthritis. Possible alternative to MOPP in combination with vinblastine, procarbazine, and prednisone.

Special Concerns: Use during lactation only if benefits outweigh risks. Safety and efficacy have not been established in children. The drug is carcinogenic in humans and may be both mutagenic and teratogenic in humans. It also affects fertility. May be cross-hypersensitivity with other alklyating agents.

Additional Side Effects: Hepatic: Hepatotoxicity with jaundice. Pulmonary: Pulmonary fibrosis bronchopulmonary dysplasia. CNS: Children with nephrotic syndrome have an increased risk of seizures. Miscellaneous: Keratitis, drug fever, sterile cystitis, interstitial pneumonia, peripheral neuropathy. Cross-sensitivity (skin rashes) may occur with other alkylating agents.

Laboratory Test Alterations: Uric acid levels in serum and urine.

Overdose Management: Symptoms: Pancytopenia (reversible), ataxia, agitated behavior, clonic-tonic seizures. Treatment: General supportive measures. Monitor blood profiles carefully; blood transfusions may be required.

How Supplied: Tablet: 2 mg

?Tablets Leukemia, lymphomas.
Individualized according to response of client. Adults, children, initial dose: 0.1-0.2 mg/kg (or 4-10 mg) daily in single or divided doses for 3-6 weeks; maintenance: 0.03-0.1 mg/kg/day depending on blood counts.
Alternative for chronic lymphocytic leukemia.
Initial: 0.4 mg/kg; then, repeat this dose every 2 weeks increasing by 0.1 mg/kg until either toxicity or control of condition is observed.
Nephrotic syndrome, immunosuppressant.
Adults, children: 0.1-0.2 mg/kg body weight daily for 8-12 weeks.
Uveitis and meningoencephalitis associated with Behcet's disease.
0.1 mg/kg/day.
Idiopathic membranous nephropathy.
0.1-0.2 mg/kg/day every other month, alternating with a corticosteroid for 6 months duration.
Rheumatoid arthritis.
0.1-0.3 mg/kg/day.

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