Chlorambucil: Indication, Dosage, Side Effect, Precaution

This information is not country-specific. Please refer to the Indonesia prescribing information.

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.

Pregnancy Category (US FDA)

PO: D

Monitoring Parameters

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:
Mechanism of Action: 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

Storage

Store between 2-8°C. This is a cytotoxic drug. Any unused portions should be disposed of in accordance w/ local requirements.

MIMS Class

Cytotoxic Chemotherapy

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.

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