BUSULFAN

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

Availability

2 mg tablets; 6 mg/mL injection

Action

Potent cytotoxic alkylating agent that may be mutagenic or carcinogenic, and 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.

Therapeutic Effect

Causes cell death by acting predominantly on slowly proliferating stem cells by inducing cross linkage in DNA, thus blocking replication.

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. Stem cell transplant conditioning.

Unlabeled Uses

Polycythemia vera, severe thrombocytosis, as adjunct in treatment of myelofibrosis, allogeneic 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; pregnancy (category D), lactation.

Cautious Use

Men and women in childbearing years; hepatic disease; 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

Stem Cell Transplant Conditioning
Adult: IV (used with cyclophosphamide) 0.8mg/kg IBW or ABW (whichever is lower) q6h x 4 d

Obesity
In severely obese patients, use adjusted ideal body weight = IBW + 0.25 x (actual weight – IBW).

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.

Intravenous

PREPARE: Intermittent: Prepare a volume of NS or D5W IV solution that is 10 times the volume of busulfan needed. Using a 5 micron nylon filter (supplied), withdraw the needed dose of busulfan. Remove needle and filter and use a new, nonfiltered needle to add busulfan to the IV fluid. (Always add busulfan to IV fluid rather than IV fluid to busulfan.) Mix by inverting the IV bag several times.

ADMINISTER: Intermittent: Infuse via a central venous catheter over 2 h. Flush line before/after infusion with at least 5 mL D5W or NS.

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 from GI tract. Peak: 4 h. Duration: 4 h. Metabolism: In liver by CYP3A4. Elimination: 10–50% 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.

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

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