Dosing and uses of Leukeran (chlorambucil)
Adult dosage forms and strengths
tablet
- 2mg
Chronic Lymphatic (Lymphocytic) Leukemia
0.1 mg/kg/day for 3-6 weeks or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response/toxicity observed) biweekly or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response observed) monthly or
0.03-0.1 mg/kg/day continuously
Reduce initial dose if administered within 4 weeks after a full course of radiation/myelosuppressive therapy or patients with bone marrow disease
Not to exceed 0.1 mg/kg/day if bone marrow infiltrated with lymphocytes
Hodgkin's Lymphoma
0.2 mg/kg/day for 3-6 weeks or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response/toxicity observed) biweekly or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response or toxicity observed) monthly or
0.03-0.1 mg/kg/day continuously
Reduce initial dose if administered within 4 weeks after a full course of radiation/myelosuppressive therapy or patients with bone marrow disease
Not to exceed 0.1 mg/kg/day if bone marrow infiltrated with lymphocytes
Renal Impairment
<1% (including metabolites) excreted in urine; no dose adjustment required
Hepatic Impairment
Primarily metabolized in liver; dose reduction may be required
Monitor
CBC
Discontinue if WBC <3000/mm³ or platelets <150,000/mm³
Other Indications & Uses
Malignant lymphomas (lymphosarcoma, giant follicular lymphoma)
Off-label: Uveitis & meningoencephalitis associeted with Behcet's disease; other NHL; idiopathic membranous nephropathy; RA
Pediatric dosage forms and strengths
tablet
- 2mg
Chronic Lymphatic (Lymphocytic) Leukemia (Off-label)
Safety and efficacy not established, but has been used unlabeled
0.1-0.2 mg/kg PO qDay
Geriatric dosage forms and strengths
Chronic Lymphatic (Lymphocytic) Leukemia
0.1 mg/kg/day for 3-6 weeks or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response/toxicity observed) biweekly or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response observed) monthly or
0.03-0.1 mg/kg/day continuously
Reduce initial dose if administered within 4 weeks after a full course of radiation/myelosuppressive therapy or patients with bone marrow disease
Not to exceed 0.1 mg/kg/day if bone marrow infiltrated with lymphocytes
Hodgkin's Lymphoma
0.2 mg/kg/day for 3-6 weeks or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response/toxicity observed) biweekly or
0.4 mg/kg (increased by 0.1 mg/kg/dose until response or toxicity observed) monthly or
0.03-0.1 mg/kg/day continuously
Reduce initial dose if administered within 4 weeks after a full course of radiation/myelosuppressive therapy or patients with bone marrow disease
Not to exceed 0.1 mg/kg/day if bone marrow infiltrated with lymphocytes
Leukeran (chlorambucil) adverse (side) effects
>10%
Neutropenia (25-33%)
Anemia
Leukopenia
Thrombocytopenia
Frequency not defined
Seizures
Hallucinations
Peripheral neuropathy
Nausea
Vomiting
Pulmonary fibrosis
GI effects
Leukemia
Myelosuppression
Hyperuricemia
Infertility
Hepatotoxicity & jaundice
Type I hypersensitivity
Rash
Stevens-Johnson syndrome (rare)
Toxic epidermal necrosis (rare)
Urticaria
Erythema multiforme (rare)
Secondary malignancies
Warnings
Black box warnings
Severe bone marrow suppression can occur with chlorambuciL
Chlorambucil is a carcinogen. Chronic therapy may produce myelocytic leukemia and secondary malignancies
Chlorambucil may cause infertility. It is teratogenic and mutagenic
Contraindications
Hypersensitivity or resistance; demonstrated resistance to chlorambucil previously
Cautions
History of seizures; head trauma; those receiving other potentially epileptogenic drugs
Potentially mutagenic, carcinogenic & teratogenic; avoid pregnancy
Can cause infertility
Severely myelosuppressive
May need lower dosages in liver failure
Beware of cross-hypersensitivity w/ other alkylating agents
Reduce dose in preexisting myelosuppressive situations or if WBC/Plt counts fall below normaL
If used within 4 week of radiation/cytotoxic chemotherapy
Avoid pregnancy
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Leukeran (chlorambucil)
Mechanism of action
Alkylating agent of nitrogen mustard family, crosslinks DNA and interferes with DNA replication and RNA transcription; cell cycle nonspecific
Absorption
Bioavailability: 70-80%
Peak Plasma Time: 1 hr
Distribution
Protein Bound: 99%
Vd: 0.3 L/kg
Metabolism
Liver
Metabolites: phenylacetic acid mustard
Elimination
Half-Life: 1.5 hr (chlorambucil); 2.5 hr (phenylacetic acid mustard)
Clearance: 492 ±160 ng/mL (chlorambucil); 306±73 ng/mL (phenylacetic acid mustard)
Excretion: Urine (20-60% metabolites)
Dialyzable: No
