CHLORAMBUCIL
| CHLORAMBUCIL (klor-am'byoo-sil) Leukeran Classifications: antineoplastic; alkylating agent; Therapeutic: antineoplastic; nitrogen mustard Prototype: Cyclophosphamide Pregnancy Category: D |
Availability
2 mg tablets
Action
Potent aromatic derivative of the alkylating agent nitrogen mustard which is slowest acting and least toxic of the nitrogen mustards. A cell-cycle nonspecific drug (kills both resting and dividing cells), it causes cytotoxic cross linkage in DNA, thus preventing synthesis of DNA, RNA, and proteins. Myelosuppression in therapeutic doses is moderate and rapidly reversible.
Therapeutic Effect
Lymphocytic effect is marked; thus it is effective in treatment of various lymphomas.
Uses
As single agent or with other antineoplastics in treatment of chronic lymphocytic leukemia, malignant lymphomas including lymphosarcoma, Hodgkin's disease, and giant follicular lymphoma, and in treatment of carcinoma of the ovary, breast, and testes.
Unlabeled Uses
Nonneoplastic conditions: vasculitis complicating rheumatoid arthritis, autoimmune hemolytic anemias associated with cold agglutinins, lupus glomerulonephritis, idiopathic nephrotic syndrome, polycythemia vera, macroglobulinemia.
Contraindications
Hypersensitivity to chlorambucil or to other alkylating agents; administration within 4 wk of a full course of radiation or chemotherapy; full dosage if bone marrow is infiltrated with lymphomatous tissue or is hypoplastic; smallpox and other vaccines; pregnancy (category D), lactation.
Cautious Use
Excessive or prolonged dosage, pneumococcus vaccination, history of seizures or head trauma.
Route & Dosage
| Malignant Diseases (Lymphomas, Hodgkin's Disease, etc.) Adult: PO 0.1–0.2 mg/kg/d (usual dose 4–10 mg/d) Child: PO 0.1–0.2 mg/kg/d in single or divided doses |
Administration
Oral- Control nausea and vomiting by giving entire daily dose at one time, 1 h before breakfast or 2 h after evening meal, or at bedtime. Consult physician.
- With confirmation of bone marrow depression (low platelet and neutrophil counts or peripheral lymphocytosis), it is recommended that dosage not exceed 0.1 mg/kg.
- Store in tightly closed, light-resistant container.
Adverse Effects (≥1%)
Body as a Whole: Drug fever, skin rashes, papilledema, alopecia, peripheral neuropathy, sterile cystitis, pulmonary complications, seizures (high doses). GI: Low incidence of gastric discomfort, hepatotoxicity. Hematologic: Bone marrow depression: leukopenia, thrombocytopenia, anemia. Metabolic: Sterility, hyperuricemia.Interactions
Drug: May have to adjust dose of allopurinol, colchicine because of chlorambucil-associated hyperuricemia.Pharmacokinetics
Absorption: Rapidly and completely from GI tract. Peak: 1 h. Distribution: Extensively bound to plasma and tissue proteins; crosses placenta. Metabolism: In liver. Elimination: 60% in urine as metabolites within 24 h. Half-Life: 1.5–2.5 h.Nursing Implications
Assessment & Drug Effects
- Lab tests: CBC, Hgb, total and differential leukocyte counts, and serum uric acid initially and at least once weekly during treatment.
- Leukopenia usually develops after the third week of treatment; it may continue for up to 10 d after last dose, then rapidly return to normal.
- Avoid or reduce to minimum injections and other invasive procedures (e.g., rectal temperatures, enemas) when platelet count is low because of danger of bleeding.
- Monitor for S&S of skin rashes, which are rare, but appear to show a consistent pattern: pustular eruption on mouth, chin, cheeks; urticarial erythema on trunk that spreads to legs. The rash occurs early in treatment period and lasts about 10 d after last dose.
Patient & Family Education
- Keep appointments with physician. During treatment it is dangerous to go longer than 2 wk without a clinical examination and blood studies.
- Notify physician if the following symptoms occur: unusual bleeding or bruising, sores on lips or in mouth; flank, stomach, or joint pain; fever, chills, or other signs of infection, sore throat, cough, dyspnea.
- Report immediately the onset of cutaneous reaction.
- Drink at least 10–12 glasses [240 mL (8 oz) each] of fluid per day, if not contraindicated, and report to physician if urine output decreases below normal amounts.
- Report to physician immediately if pregnant, as there is a potential hazard to the fetus.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug