BUSULFAN
(byoo-sul'fan)
Busulfex, Myleran
Classifications: antineoplastic; alkylating agent
Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

2 mg tablets; 6 mg/mL injection

Actions

Potent cytotoxic alkylating agent that may be mutagenic and carcinogenic. Cell cycle nonspecific. Reduces total granulocyte mass but has little effect on lymphocytes and platelets except in large doses. May cause widespread epithelial cellular dysplasia severe enough to make it difficult to interpret exfoliative cytologic examinations from lung, breast, bladder, and uterine cervix.

Therapeutic Effects

Causes cell death by acting predominantly on slowly proliferating stem cells by inducing cross linkage in DNA, thus blocking replication. Acquired resistance may develop, probably due to intracellular inactivation of busulfan.

Uses

Palliative treatment of chronic myelogenous (myeloid, granulocytic, myelocytic) leukemia for patients no longer responsive to radiation therapy or to previously tried antineoplastics. Does not appreciably extend survival time.

Unlabeled Uses

Polycythemia vera, severe thrombocytosis, as adjunct in treatment of myelofibrosis, allogenic bone transplantation in patients with acute nonlymphocytic leukemia.

Contraindications

Therapy-resistant chronic lymphocytic leukemia; lymphoblastic crisis of chronic myelogenous leukemia; bone marrow depression, immunizations (patient and household members), chickenpox (including recent exposure), herpetic infections. Safety during pregnancy (category D) or lactation is not established.

Cautious Use

Men and women in childbearing years; history of gout or urate renal stones; prior irradiation or chemotherapy.

Route & Dosage

Chronic Myelogenous Leukemia
Adult: PO 4–8 mg/d until maximal clinical and hematologic improvement, may use 1–4 mg/d if remission is shorter than 3 mo
Child: PO 0.06–0.12 mg/kg/d or 1.8–4.6 mg/m²

Administration

Oral

Give at same time each day.
Give on an empty stomach to minimize nausea and vomiting.
Store in tightly capped, light-resistant container at 15°–30° C (59°–86° F), unless otherwise specified.

Adverse Effects (1%)

Hematologic: Major toxic effects are related to bone marrow failure; agranulocytosis (rare), pancytopenia, thrombocytopenia, leukopenia, anemia. Urogenital: Flank pain, renal calculi, uric acid nephropathy, acute renal failure, gynecomastia, testicular atrophy, azoospermia, impotence, sterility in males, ovarian suppression, menstrual changes, amenorrhea (potentially irreversible), menopausal symptoms. Respiratory: Irreversible pulmonary fibrosis ("busulfan lung"). Skin: Alopecia, hyperpigmentation. Other: Endocardial fibrosis, dizziness, cholestatic jaundice, infections.

Diagnostic Test Interference

Busulfan may decrease urinary 17-OHCS excretion, and may increase blood and urine uric acid levels. Drug-induced cellular dysplasia may interfere with interpretation of cytologic studies.

Interactions

Drug: Probenecid, sulfinpyrazone may increase uric acid levels.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 4 h. Duration: 4 h. Metabolism: Metabolized in liver. Elimination: 10–50% excreted in urine within 48 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness: Normal leukocyte count is usually achieved in about 2 mo.
Monitor the following: Vital signs, weight, I&O ratio and pattern. Urge patient to increase fluid intake to 10–12 [8 oz] glasses daily (if allowed) to assure adequate urinary output.
Monitor for and report symptoms suggestive of superinfection (see Appendix F), particularly when patient develops leukopenia.
Lab test: Baseline Hgb, Hct, WBC with differential, platelet count, liver function, kidney function, serum uric acid; repeat at least weekly.
Avoid invasive procedures during periods of platelet count depression.

Patient & Family Education

Report to physician any of the following: Easy bruising or bleeding, cloudy or pink urine, dark or black stools; sore mouth or throat, unusual fatigue, blurred vision, flank or joint pain, swelling of lower legs and feet; yellowing white of eye, dark urine, light-colored stools, abdominal discomfort, or itching (hepatotoxicity).
Use contraceptive measures during busulfan therapy and for at least 3 mo after drug is withdrawn.
Do not breast feed while taking this drug without consulting physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug