chlorambucil
Leukeran

Pharmacologic classification: alkylating agent (not specific to phase of cell cycle)
Therapeutic classification: antineoplastic
Pregnancy risk category D


Available forms
Available by prescription only
Tablets (sugar-coated): 2 mg

Indications and dosages
  Dosages and indications may vary. Check current literature for recommended protocol.
 Chronic lymphocytic leukemia; malignant lymphomas including lymphosarcoma, giant follicular lymphomas, and Hodgkin’s disease. Adults: 100 to 200 mcg/kg P.O. daily or 3 to 6 mg/m2 P.O. daily as a single dose or in divided doses for 3 to 6 weeks. Usual dose is 4 to 10 mg daily. Reduce dose if full course of radiation therapy is planned within 4 weeks.
 Minimal change nephrotic syndrome ◇. Children: 100 to 200 mcg/kg P.O. daily for 8 to 12 weeks with prednisone. Maximum 8.2 mg/kg to 14 mg/kg in one course of therapy.
 Macroglobulinemia ◇. Adults: 2 to 10 mg P.O. daily.
 Metastatic trophoblastic neoplasia ◇. Adults: 6 to 10 mg P.O. daily for 5 days; repeat q 1 to 2 weeks.
 Idiopathic uveitis, Behçet’s syndrome ◇. Adults: 6 to 12 mg P.O. daily for 1 year.
 Rheumatoid arthritis ◇. Adults: 0.1 to 0.3 mg/ kg P.O. daily.

Pharmacodynamics
Antineoplastic action: Drug exerts its cytotoxic activity by cross-linking strands of cellular DNA and RNA, disrupting normal nucleic acid function.

Pharmacokinetics
Absorption: Well absorbed from the GI tract.
Distribution: Not well understood. However, drug and its metabolites have been shown to be highly bound to plasma and tissue proteins.
Metabolism: Metabolized in the liver. Its primary metabolite, phenylacetic acid mustard, also possesses cytotoxic activity.
Excretion: Metabolites are excreted in urine. Half-life of parent compound is 2 hours; the phenylacetic acid metabolite, 2 1/2 hours.

Route Onset Peak Duration
P.O. Unknown 1 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug or resistant to previous therapy. Patients hypersensitive to other alkylating agents also may be hypersensitive to drug. Use cautiously in patients with history of head trauma or seizures and in those receiving other drugs that lower seizure threshold.

Interactions
Drug-drug. Anticoagulants, aspirin: Increases risk of bleeding. Avoid use together.
Myelosuppressives: May cause additive myelosuppression when used together. Monitor patient closely.

Adverse reactions
CNS: seizures, peripheral neuropathy, tremor, muscle twitching, confusion, agitation, ataxia, flaccid paresis.
GI: nausea, vomiting, stomatitis, diarrhea.
GU: azoospermia, infertility.
Hematologic: neutropenia, delayed up to 3 weeks, lasting up to 10 days after last dose; bone marrow suppression; thrombocytopenia; anemia.
Hepatic: hepatotoxicity.
Respiratory: interstitial pneumonitis.
Skin: rash.
Other: allergic febrile reaction, hypersensitivity reaction.

Effects on lab test results
• May increase AST and alkaline phosphatase levels. May increase blood and urine uric acid levels.
• May decrease hemoglobin, hematocrit, and neutrophil and platelet counts. May decrease WBC, granulocyte, and RBC counts.

Overdose and treatment
Evidence of overdose includes reversible pancytopenia in adults, and vomiting, ataxia, abdominal pain, muscle twitching, and major motor seizures.
 Treatment is usually supportive with transfusion of blood components, if needed, and appropriate anticonvulsant therapy if seizures occur. Induction of emesis, activated charcoal, and gastric lavage may be useful in removing unabsorbed drug. Drug is not dialyzable.

Special considerations
• Oral suspension can be prepared in the pharmacy by crushing tablets and mixing powder with a suspending agent and simple syrup.
• I.M. injections shouldn’t be given when platelets are below 50,000/mm3.
• To prevent hyperuricemia with resulting uric acid nephropathy, allopurinol may be used with adequate hydration.
• Store tablets in a tightly closed, light-resistant container.
• Monitor CBC at least weekly during treatment and leukocyte counts 3 to 4 days after each weekly CBC for the first 3 to 6 weeks of treatment.
• In patients receiving intermittent therapy, perform CBC once weekly for 3 months, then at least once every 4 weeks.
• Drug-induced pancytopenia generally lasts 1 to 2 weeks but may persist for 3 to 4 weeks. It’s reversible up to a cumulative dose of 6.5 mg/kg in a single course.
Pregnant patients
• Drug should be used in life-threatening cases or when safer drugs can’t be used or are ineffective. Inform patient of potential hazards to fetus.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Consider the risk of serious adverse reactions, mutagenicity, and carcinogenicity in breast-fed infants and the woman’s need for the drug in deciding whether to discontinue drug or breast-feeding.
Pediatric patients
• Safety and efficacy in children haven’t been established. The potential benefits versus risks must be evaluated.

Patient education
• Emphasize importance of continuing medication despite nausea and vomiting, and of keeping appointments for periodic blood work.
• Advise patient to report vomiting that occurs shortly after taking a dose or symptoms of infection or bleeding.
• Tell patient to immediately report skin reactions or rash.
• Caution patient to avoid exposure to people with infections.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use