Chlorambucil

Pronunciation: (klor-AM-byoo-sill)
Class: Nitrogen mustard

Trade Names

Leukeran
- Tablets 2 mg

Pharmacology

Chlorambucil is a bifunctional alkylating agent of the nitrogen mustard type. A cell cycle nonspecific drug, chlorambucil interacts with cellular DNA to produce a cytotoxic cross-linkage.

Pharmacokinetics

Absorption

Rapidly and completely absorbed. T _max is within 1 h. C _max is about 1 mcg/mL.

Distribution

99% protein bound (albumin). Crosses the placenta.

Metabolism

Rapidly and extensively metabolized in the liver to phenylacetic acid mustard (active).

Elimination

The t _½ is 1.5 h (chlorambucil) and 2.4 h (phenylacetic acid mustard). 15% to 60% is excreted in urine after 24 h (less than 1% as chlorambucil or phenylacetic acid mustard).

Indications and Usage

Chronic lymphatic leukemia; malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin disease.

Unlabeled Uses

Ovarian and testicular carcinoma, non-Hodgkin lymphoma, Waldenström macroglobulinemia.

Contraindications

Prior resistance or hypersensitivity.

Dosage and Administration

Initial Treatment
Adults

PO 0.1 to 0.2 mg/kg/day (4 to 10 mg/day) for 3 to 6 wk. Hodgkin disease usually requires 0.2 mg/kg/day, whereas lymphomas or chronic lymphocytic leukemia usually require 0.1 mg/kg/day.

Maintenance
Adults

PO Doses should not exceed 0.1 mg/kg/day and may be as low as 0.03 mg/kg/day. Doses of 2 to 4 mg/day are typical.

General Advice

• Diligently follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs.
• Prescribed dose may be given at one time.
• Administer without regard to meals but administer with food if GI upset occurs.

Storage/Stability

Store tablets in refrigerator (36° to 46°F).

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Confusion; agitation; ataxia; hallucinations; tremors; muscular twitching; flaccid paresis; peripheral neuropathy; seizures; myoclonia.

Dermatologic

Rash; urticaria; skin hypersensitivity (including rare reports of skin rash progressing to erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome).

GI

Nausea; vomiting; diarrhea; oral ulceration; mucositis.

Genitourinary

Sterile cystitis; reversible and permanent sterility.

Hematologic

Bone marrow suppression; leukemia.

Hepatic

Hepatotoxicity; jaundice.

Hypersensitivity

Angioedema.

Respiratory

Interstitial pneumonia; pulmonary fibrosis.

Miscellaneous

Acute myelogenous leukemia; drug fever; secondary malignancies.

Precautions

Warnings Bone marrow damage Chlorambucil can severely suppress bone marrow function. Carcinogenesis Because of its carcinogenic properties, do not give to patients with conditions other than chronic lymphatic leukemia or malignant lymphomas. Fertility Chlorambucil has caused chromatid or chromosome damage in men. Reversible and permanent sterility have occurred in men and women. Mutagenicity and teratogenicity Probable in humans.

Monitor Cumulative dose Document total cumulative dose. Infection Monitor patient for signs and symptoms of bacterial, viral, or fungal infection. Report to health care provider immediately if noted. WBC/Platelet count Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Chromosome damage

Chromosome or chromatid damage may occur.

Contraception

Ensure women of childbearing potential are not pregnant when therapy is initiated and are using effective contraception during treatment.

Dermatologic

Skin rash progressing to erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome may occur.

Hypoplastic bone marrow/Infiltration

Ensure that daily dose does not exceed 0.1 mg/kg in patient with confirmed hypoplastic bone marrow or bone marrow infiltration.

Radiation and chemotherapy

Do not give a full dosage before 4 wk after a full course of radiation therapy or chemotherapy because of the vulnerability of the bone marrow to damage under these conditions.

Seizures

Rare, focal, or generalized seizures have occurred in adults and children at therapeutic daily doses, pulse dosing regimens, and in acute overdosage. Exercise caution when administering chlorambucil to patients with a history of seizure disorders, head trauma, or to patients receiving other potentially epileptogenic drugs.

Overdosage

Symptoms

Reversible pancytopenia, neurological toxicity ranging from agitated behavior and ataxia to multiple grand mal seizures.

Patient Information

• Explain name, action, and potential adverse reactions of the treatment regimen. Review the treatment regimen including dosing schedule, duration of treatment, and monitoring that will be required.
• Review benefits of therapy and risks, including potential infertility, leukemia, or secondary malignancies.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: skin rash; difficulty breathing; fever, chills, or other signs of infection; bleeding or unusual or bruising; seizures; yellow discoloration of skin or eyes; unusual lumps or masses.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, or diarrhea; persistent cough; loss of menstruation.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Advise men that therapy may temporarily or permanently impair their fertility.

Copyright © 2009 Wolters Kluwer Health.