Class: Antineoplastic Agents
VA Class: AN100
CAS Number: 305-03-3
May severely suppress bone marrow function.107 (See Hematologic Effects under Cautions.)
Known carcinogen.107 (See Carcinogenicity under Cautions.)
May cause fetal harm.107 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
May cause male or female infertility.107 (See Fertility under Cautions.)
Antineoplastic agent; nitrogen mustard derivative; alkylating agent.107
Uses for Chlorambucil
Chronic Lymphocytic Leukemia (CLL)
Treatment (with or without corticosteroids) of indolent, noncontiguous stage II–IV adult non-Hodgkin’s lymphomas (e.g., follicular lymphoma).b
Not curative; rate of relapse is constant over time, even in complete responders.b
Optimal treatment as yet unknown; defer treatment in asymptomatic patient and monitor carefully.b
Minimal-change Nephrotic Syndrome
Second-line agent; use only in those with severe, corticosteroid-dependent or frequently relapsing disease who are intolerant of corticosteroid therapy or whose disease is corticosteroid resistant.a
Some clinicians prefer cyclophosphamide to chlorambucil.a
Chlorambucil Dosage and Administration
Optimize results and minimize adverse effects by basing dose on clinical and hematologic response, patient tolerance, and other chemotherapy or irradiation being used.107
Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.107
May administer high doses in intermittent regimens at bedtime with antiemetics to minimize adverse GI effects.a
Minimal-change Nephrotic Syndrome†
Usual dosage: 0.1–0.2 mg/kg once daily with varying dosages of prednisone for 8–12 weeks; additional course of therapy may be necessary.a
Reduce initial dosage if administered within 4 weeks after full course of radiation therapy or myelosuppressive drugs or if pretreatment leukocyte or platelet counts are depressed from bone marrow disease.107 a
Continuous regimen: 0.1–0.2 mg/kg (4–10 mg daily for average patient) given as a single daily dose; usually requires only 0.1 mg/kg daily.107
Biweekly (once every 2 weeks) regimen: initially, 0.4 mg/kg; increase doses by 0.1 mg/kg every 2 weeks until a response and/or myelosuppression occurs.a Adjust subsequent dosages to produce mild myelosuppression.a
Therapy usually continued for 3–12 months regardless of regimen and schedule used.a Generally discontinued after 1 year and restarted when the disease relapses (in patients who achieved a complete remission) or continued as needed (in those who achieved only a partial response).a
Usual dosage: 0.1–0.2 mg/kg given as a single daily dose for 3–6 weeks; usually requires 0.2 mg/kg daily.107
Usual dosage: 0.1–0.2 mg/kg given as a single daily dose for 3–6 weeks; usually requires only 0.1 mg/kg daily.107
Continuous therapy: 0.1 mg/kg daily.d
Intermittent therapy: 0.3 mg/kg daily for 7 days every 6 weeks.d
Therapy usually continued for at least several months regardless of regimen used; optimal duration unknown.d
Minimal-change Nephrotic Syndrome†
Maximum total dosage during a single course of therapy: 8.2–14 mg/kg.a
Daily dose should not exceed 0.1 mg/kg (about 6 mg for average patient) in the presence of lymphocytic infiltration of the bone marrow or hypoplastic bone marrow.107
Cautions for Chlorambucil
Known hypersensitivity to chlorambucil or any ingredient in the formulation.107
Disease resistant to prior chlorambucil therapy.107
Possible leukemia or secondary malignancies; assess risk/benefits of therapy.107
Not recommended by manufacturer for the treatment of nonmalignant diseases.107
Fetal/Neonatal Morbidity and Mortality
Amenorrhea reported in females.107
Possible angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria.107
Potential for cross-sensitivity (rash) between chlorambucil and other alkylating agents.a
Discontinue promptly if skin reaction develops.107
Slowly progressive lymphopenia is common; return to normal lymphocyte counts generally occurs rapidly after completion of therapy.107
Possible dose-dependent, reversible neutropenia after third week of continuous therapy and continuing for up to 10 days after last dose.107
Adverse hematologic effects may be less severe with intermittent dosing than with continuous dosing.a
If leukocyte count falls abruptly or leukocyte or platelet counts fall below normal values, decrease chlorambucil dosage; discontinue drug for more severe depression.107
Possible increased risk of seizures in children with nephrotic syndrome and patients receiving high pulse doses of chlorambucil.107
Use with caution in patients with a history of seizures or head trauma or those receiving other potentially epileptogenic drugs.107
Prior Irradiation or Myelosuppressive Therapy
Possible additive myelosuppressive effects; do not administer at full dosages within 4 weeks after a full course of radiation therapy or myelosuppressive drugs.107
Adequate Patient Evaluation and Monitoring
Monitor hematologic status carefully.107
Avoid administration of live vaccines to immunocompromised patients.107
Category D.107 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Not known whether chlorambucil is distributed into milk; discontinue nursing or the drug.107
Possible increased risk of seizures in children with nephrotic syndrome; use with caution in those with a history of seizure disorder or head trauma or receiving concomitant therapy with drugs that lower seizure threshold.107
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults;107 titrate dosage carefully, due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.107
Common Adverse Effects
Bone marrow suppression.107
Rapidly and completely absorbed from GI tract.107
Not fully characterized.107
Plasma Protein Binding
Approximately 99% (mainly albumin).107
Rapidly and extensively metabolized in the liver, principally to phenylacetic acid mustard (pharmacologically active).107 Chlorambucil and phenylacetic acid mustard converted to mono- and dihydroxy derivatives.107
Excreted in urine (15–60%) almost completely as metabolites.107
Chlorambucil: 1.3–1.5 hours.107
Phenylacetic acid mustard: 1.8 hours.107
Interferes with DNA replication and transcription of RNA; ultimately results in disruption of nucleic acid function.a
Possesses some immunosuppressive activity, principally due to suppression of lymphocytes.a
The slowest acting and generally least toxic of the currently available nitrogen mustard derivatives.a
Advice to Patients
Risk of hypersensitivity, drug fever, myelosuppression, hepatotoxicity, infertility, seizures, GI toxicity, and secondary malignancies.107
Importance of informing clinicians if rash, bleeding, fever, jaundice, persistent cough, seizures, nausea, vomiting, amenorrhea, or unusual lumps or masses occur.107
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy.107
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.107
Importance of informing patients of other important precautionary information.107 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Leukeran 2MG Tablets (PRASCO LABORATORIES): 30/$134.99 or 90/$374.95
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions July 1, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Only references cited for selected revisions after 1984 are available electronically.
100. Ponticelli C, Zucchelli P, Imbasciati E et al. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med. 1984; 310:946-50. [IDIS 183239] [PubMed 6366560]
101. Godfrey WA, Epstein WV, O’Connor GR et al. The use of chlorambucil in intractable idiopathic uveitis. Am J Ophthalmol. 1974; 78:415-28. [IDIS 45882] [PubMed 4472398]
102. Mamo JG, Azzam SA. Treatment of Behcet’s disease with chlorambucil. Arch Ophthalmol. 1970; 84:446-50. [IDIS 14388] [PubMed 5492448]
103. Mamo JG. Treatment of Behcet disease with chlorambucil. Arch Ophthalmol. 1976; 94:580-3. [IDIS 69536] [PubMed 1267637]
104. O’Duffy JD, Robertson DM, Goldstein NP. Chlorambucil in the treatment of uveitis and meningoencephalitis of Behcet’s disease. Am J Med. 1984; 76:75-84. [IDIS 180408] [PubMed 6691363]
105. Ponticelli C, Zucchelli P, Passerini P et al. A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. N Engl J Med. 1989; 320:8-13. [IDIS 249967] [PubMed 2642605]
106. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. [PubMed 15529105]
107. GlaxoSmithKline. Leukeran (chlorambucil) tablets prescribing information. Research Triangle Park, NC; 2004 Nov.
108. Chronic lymphocytic leukemia. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2001 Jun.
109. Dighiero G, Maloum K, Desablens B et al. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998; 338:1506-14. [IDIS 405094] [PubMed 9593789]
110. CLL Trialists’ Collaborative Group. Chemotherapeutic options in chronic lymphocytic leukemia: a meta-analysis of the randomized trials. J Natl Cancer Inst. 1999; 91:861-8. [PubMed 10340906]
111. Adult non-Hogkin’s lymphoma. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2001 Oct.
112. Mycosis fungoides and the Sezary syndrome. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2001 Sep.
a. AHFS drug information 2005. McEvoy GK, ed. Chlorambucil. Bethesda, MD: American Society of Health-System Pharmacists; 2005:944-8.
b. Adult non-Hogkin’s lymphoma. From: CancerNet/PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2003 Sep 26.
d. Dimopoulos M. Waldenström’s macroglobulinemia therapy. Hema 99. From the American Society of Hematology website. Accessed 2003 Dec 15.