P - Contraindicated in pregnancy
L - Contraindicated in lactation
Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia. It is a nitrogen mustard alkylating agent and can be given orally.
In the past, chlorambucil has been used for treating some types of non-Hodgkin lymphoma, Waldenström macroglobulinemia, polycythemia vera, trophoblastic neoplasms, and ovarian carcinoma. It also has been used as an immunosuppressive drug for various autoimmune and inflammatory conditions, such as nephrotic syndrome. Its current use is mainly in chronic lymphocytic leukemia, as it is well tolerated by most patients, though chlorambucil has been largely replaced by fludarabine as first-line treatment in younger patients.
Chlorambucil interferes with DNA replication and RNA transcription by alkylation and cross-linking cellular DNA strands, thus leading to disruption of the nucleic acid function.
Absorption: Rapid and almost complete from the GI tract (oral).
Distribution: Protein-binding: Extensive.
Metabolism: Extensively hepatic; converted to phenylacetic acid mustard.
Excretion: Urine (as metabolites and unchanged drug); 1.5 hr (elimination half-life).
Reversible progressive lymphocytopenia and neutropenia; GI disturbances; hepatotoxicity; skin rashes; peripheral neuropathy; central neurotoxicity including seizures; interstitial pneumonia, pulmonary fibrosis. High doses may produce azoospermia and amenorrhoea. Sterility when given to boys at or before puberty.
Potentially Fatal: Severe bone marrow suppression, carcinogenic and human infertility.
Bone marrow damage
Chlorambucil can severely suppress bone marrow function.
Because of its carcinogenic properties, do not give to patients with conditions other than chronic lymphatic leukemia or malignant lymphomas.
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.
Document total cumulative dose.
Monitor patient for signs and symptoms of bacterial, viral, or fungal infection. Report to health care provider immediately if noted.
Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops.
Chromosome or chromatid damage may occur.
Ensure women of childbearing potential are not pregnant when therapy is initiated and are using effective contraception during treatment.
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.
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.
Reversible pancytopenia, neurological toxicity ranging from agitated behavior and ataxia to multiple grand mal seizures.
Renal or hepatic dysfunction. Perform blood counts regularly. Seizure disorder, bone marrow suppression. Patient who has received radiation therapy, myelosuppressive drugs or has a depressed baseline leukocyte/platelet count within the previous 4 wk. Increased incidence of acute leukaemias and other secondary malignancies.
Impairs immune response to vaccines, possible infection after admin of live vaccines.
Adult: 200 mcg/kg daily. Not to exceed 100 mcg/kg/day if the bone marrow is hypoplastic or if there is lymphocytic infiltration in the bone marrow. Once remission is establised, start maintenance at 30-100 mcg/kg/day.
Adult: 100 mcg/kg daily. Not to exceed 100 mcg/kg/day if the bone marrow is hypoplastic or if there is lymphocytic infiltration in the bone marrow. Once remission is establised, start maintenance at 30-100 mcg/kg/day.
Chronic lymphocytic leukaemia
Adult: 100-200 mcg/kg daily (usually 4-10 mg once daily) for 3-8 wk. Not to exceed 100 mcg/kg/day if the bone marrow is hypoplastic or if there is lymphocytic infiltration in the bone marrow. Once remission is establised, start maintenance at 30-100 mcg/kg/day.
Adult: Initially, 6-12 mg daily until leucopenia develops. Maintenance: 2-8 mg daily.
Should be taken on an empty stomach. (Take on an empty stomach. Ensure adequate hydration. Swallow whole, do not chew/crush.)
Contraindicated in pregnancy.
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Contraindicated in lactation
Information Not Available
Information Not Available
Hypersensitivity. Pregnancy and lactation. Porphyria.
May cause reversible pancytopenia. Neurological toxicity ranging from agitated behavior and ataxia to multiple grand mal seizures may also occur. Management includes monitoring CBC closely and general supportive measures. Appropriate blood transfusions may be given, if necessary. Chlorambucil is not dialysable.
Oral: Refrigerate at 2-8°C
Oral: Refrigerate at 2-8°C