Chlorambucil


Generic Medicine Info
Indications and Dosage
Oral
Hodgkin's disease
Adult: 200 mcg/kg daily for 4-8 wk. Daily dose should not exceed 100 mcg/kg if the bone marrow presents w/ lymphocyte infiltration or is hypoplastic. Maintenance: 30-100 mcg/kg daily, once remission is established.
Elderly: Initiate at lower end of dosage range.

Oral
Non-Hodgkin's lymphoma
Adult: 100 mcg/kg daily for 4-8 wk. Daily dose should not exceed 100 mcg/kg if the bone marrow presents w/ lymphocyte infiltration or is hypoplastic. Maintenance: 30-100 mcg/kg daily, once remission is established.
Elderly: Initiate at lower end of dosage range.

Oral
Waldenstrom's macroglobulinaemia
Adult: Initially, 6-12 mg daily until leucopenia occurs. Maintenance: 2-8 mg daily indefinitely.
Elderly: Initiate at lower end of dosage range.

Oral
Chronic lymphocytic leukaemia
Adult: 150 mcg/kg daily until total leucocyte count falls to 10,000 cells/mm3. Daily dose should not exceed 100 mcg/kg if the bone marrow presents w/ lymphocyte infiltration or is hypoplastic. Maintenance: 30-100 mcg/kg daily once remission is established. Alternatively, an initial single dose of 400 mcg/kg, increased by 100 mcg/kg at each 2- or 4-wk dose interval until control of lymphocytosis or toxicity occurs.
Elderly: Initiate at lower end of dosage range.
Hepatic Impairment
Severe: Dose reduction may be necessary.
Administration
Should be taken on an empty stomach. Ensure adequate hydration. Swallow whole, do not chew/crush.
Contraindications
Lactation.
Special Precautions
Patient w/ history of seizure disorder or head trauma, nephrotic syndrome, and those receiving high-pulse therapy. Patient who has recently undergone radiotherapy or received other cytotoxic agents. Admin of live vaccines. Severe hepatic or renal impairment. Childn and elderly. Pregnancy.
Adverse Reactions
Significant: Myelosuppresion, infertility (i.e. sterility in prepubertal/pubertal males, azoospermia in adult males, amenorrhoea), secondary malignancy (e.g. acute leukaemia). Rarely, focal and/or generalised seizures, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis.
Nervous: Peripheral neuropathy, agitation, ataxia.
GI: Nausea, vomiting, diarrhoea, abdominal pain, anorexia, oral ulceration.
Resp: Interstitial pneumonia.
Hepatic: Hepatotoxicity, jaundice.
Genitourinary: Sterile cystitis.
Haematologic: Leucopenia (i.e. neutropenia, lymphopenia), thrombocytopenia, anaemia, pancytopenia, irreversible bone marrow failure.
Dermatologic: Rash, urticaria, angioedema, dermatitis, pruritus, occurrence or exacerbation of herpes zoster.
Others: Hyperuricaemia, drug fever.
Potentially Fatal: Rarely, pulmonary fibrosis.
MonitoringParameters
Perform CBC (w/ differential) wkly while closely monitoring WBC 2 wkly during first 3-6 wk of treatment; and LFTs.
Overdosage
Symptoms: Reversible pancytopenia, agitation, ataxia, multiple grand mal seizures. Management: Supportive treatment w/ appropriate blood transfusion if necessary.
Food Interaction
Reduced absorption w/ food.
Action
Description: Chlorambucil is an alkylating agent that is derived from chlormethine. It interferes w/ DNA replication and RNA transcription by alkylation and cross-linking the cellular DNA strands, thereby leading to disruption of the nucleic acid function.
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed from the GI tract. Decreased absorption w/ food. Bioavailability: Approx 70-100%. Time to peak plasma concentration: W/in 1 hr.
Distribution: Volume of distribution: Approx 0.3 L/kg. Plasma protein binding: Approx 99%, mainly to albumin.
Metabolism: Extensively metabolised in the liver via monodichloroethylation and β-oxidation, mainly to the active metabolite, phenylacetic acid mustard; may undergo spontaneous degradation to other metabolites.
Excretion: Via urine (approx 20-60%, mainly as inactive metabolites, <1% as unchanged drug or phenylacetic acid mustard). Terminal elimination half-life: Approx 1.5 hr.
Chemical Structure

Chemical Structure Image
Chlorambucil

Source: National Center for Biotechnology Information. PubChem Database. Chlorambucil, CID=2708, https://pubchem.ncbi.nlm.nih.gov/compound/Chlorambucil (accessed on Jan. 21, 2020)

Storage
Store between 2-8°C. This is a cytotoxic drug. Any unused portions should be disposed of in accordance w/ local requirements.
ATC Classification
L01AA02 - chlorambucil ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
References
Anon. Chlorambucil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/02/2017.

Buckingham R (ed). Chlorambucil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/02/2017.

Joint Formulary Committee. Chlorambucil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/02/2017.

Leukeran Tablet, Film Coated (Aspen Global Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/02/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Chlorambucil. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 20/02/2017.

Disclaimer: This information is independently developed by MIMS based on Chlorambucil from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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