byoo-SUL-fan

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

• PO: Chronic myelogenous leukemia (CML) and bone marrow disorders.
• IV: Conditioning regimen before allogenic hematopoietic progenitor cell transplantation for CML (in combination with cyclophosphamide).

• Disrupts nucleic acid function and protein synthesis (cell-cycle phase–nonspecific).

• Death of rapidly growing cells, especially malignant ones.

Absorption: Rapidly absorbed from the GI tract following oral administration. IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized by the liver.

Half-life: 2.5 hr.

(effect on blood counts)

†Complete recovery may take up to 20 mo.

†After administration of last dose.

Contraindicated in:

• Hypersensitivity
• Failure to respond to previous courses
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Active infection
• ↓bone marrow reserve
• Obese patients (base dose on ideal body weight)
• Other chronic debilitating diseases
• Women of reproductive potential and men with female partners of reproductive potential
• Geri: Begin therapy at lower end of dose range in older adults due to ↑ frequency of impaired cardiac, hepatic, or renal function.

Incidence and severity of adverse reactions and side effects are increased with IV use

CV: PO: CARDIAC TAMPONADE (WITH HIGH-DOSE CYCLOPHOSPHAMIDE).
IV: chest pain, hypotension, tachycardia, thrombosis, arrhythmias, atrial fibrillation, cardiomegaly, ECG changes, edema, heart block, HF, hypertension, pericardial effusion, ventricular extrasystoles.

Derm: PO: itching, rash, acne, alopecia, erythema nodosum, exfoliative dermatitis, hyperpigmentation.

EENT: PO: cataracts.
IV: epistaxis, pharyngitis, ear disorders.

Endo: PO and IV: hyperuricemia.
IV: hyperglycemia.
PO: sterility, gynecomastia.

F and E: hypokalemia, hypomagnesemia, hypophosphatemia.

GI: PO: drug-induced hepatitis, nausea, vomiting.
IV: abdominal enlargement, anorexia, constipation, diarrhea, dry mouth, hematemesis, nausea, rectal discomfort, vomiting, abdominal pain, dyspepsia, hepatic veno-occlusive disease (↑ in allogenic transplantation), hepatomegaly, pancreatitis, stomatitis.

GU: oliguria, dysuria, hematuria, ↓ fertility.

Hemat: BONE MARROW DEPRESSION.

Local: inflammation/pain at injection site.

MS: arthralgia, myalgia, back pain.

Neuro: IV: anxiety, confusion, depression, dizziness, headache, weakness., CEREBRAL HEMORRHAGE/COMA, encephalopathy, mental status changes, SEIZURES.

Resp: PO: PULMONARY FIBROSIS.
IV: alveolar hemorrhage, asthma, atelectasis, cough, hemoptysis, hypoxia, pleural effusion, pneumonia, rhinitis, sinusitis.
Misc: allergic reactions, chills, fever, infection.

Drug-Drug:

• Concurrent or previous (within 72 hr) use of acetaminophen may ↓ elimination and ↑ toxicity.
• Concurrent use with high-dose cyclophosphamide in patients with thalassemia may result in cardiac tamponade.
• Itraconazole, metronidazole, or deferasirox may ↑ levels and risk of toxicity.
• Phenytoin may ↓ levels and effectiveness.
• Long-term continuous therapy with thioguanine may ↑ risk of hepatic toxicity.
• ↑bone marrow suppression with other antineoplastics or radiation therapy.
• May ↓ the antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

• PO (Adults): Induction: 1.8 mg/m²/day or 0.06 mg/kg/day until WBCs <15,000/mm³. Usual dose is 4–8 mg/day (range 1–12 mg/day). Maintenance: 1–3 mg/day.
• PO (Children): 0.06–0.12 mg/kg/day or 1.8–4.6 mg/m²/day initially. Titrate dose to maintain WBC of approximately 20,000/mm³.
• IV (Adults): 0.8 mg/kg every 6 hr (dose based on ideal body weight or actual weight, whichever is less; in obese patients, dosage should be based on adjusted ideal body weight) for 4 days (total of 16 doses); given in combination with cyclophosphamide.

(Generic available)

• Tablets: 2 mg;
• Solution for injection: 6 mg/mL;

• High Alert:Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for at least 10 min. Assess for signs of infection (fever, chills, sore throat, cough, hoarseness, lower back or side pain, difficult or painful urination) during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension. Notify health care professional if these symptoms occur.
• Monitor intake and output ratios and daily weights. Report significant changes in totals.
  • Monitor for symptoms of gout (increased uric acid, joint pain, lower back or side pain, swelling of feet or lower legs). Encourage patient to drink at least 2 L of fluid each day. Allopurinol may be given to decrease uric acid levels. Alkalinization of urine may be ordered to increase excretion of uric acid.
  • Assess for pulmonary fibrosis (fever, cough, shortness of breath) periodically during and after therapy. Discontinue therapy at the first sign of pulmonary fibrosis. Usually occurs 8 mo–10 yr (average 4 yr) after initiation of therapy.

• Monitor CBC with differential and platelet count before and weekly during therapy. The nadir of leukopenia occurs within 10–15 days and the nadir of WBC at 11–30 days. Recovery usually occurs within 12–20 wk. Notify health care professional if WBC is <15,000/mm³ or if a precipitous drop occurs. Institute thrombocytopenia precautions if platelet count is <150,000/mm³. Bone marrow depression may be severe and progressive, with recovery taking 1 mo–2 yr after discontinuation of therapy.
  • Monitor serum ALT, bilirubin, alkaline phosphatase, and uric acid before and periodically during therapy. May cause ↑ uric acid levels.
  • May cause false-positive cytology results of breast, bladder, cervix, and lung tissues.

• High Alert:Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations, and infusion pump settings.
• High Alert:Do not confuse Myleran with Leukeran.
• IV: Premedicate patient with phenytoin before IV administration to minimize the risk of seizures.
  • Administer antiemetics before IV administration and on a fixed schedule during IV administration.
• PO: Administer at the same time each day. Administer on an empty stomach to decrease nausea and vomiting.

IV Administration:

• IV: Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
• Intermittent Infusion: Dilute with 10 times the volume of busulfan using 0.9% NaCl or D5W. 0.5 mg/mL. When drawing busulfan from vial, use needle with 5-micron nylon filter provided, remove calculated volume from vial, remove needle and filter, replace needle and inject busulfan into diluent. Do not use polycarbonate syringes with busulfan. Only use filters provided with busulfan. Always add busulfan to diluent, not diluent to busulfan. Add 9.3 mL busulfan to 93 mL of 0.9 NaCl or D5W for final solution. Mix by inverting several times. Before and after infusion, flush catheter with 5 mL of 0.9% NaCl or D5W. Solution diluted with 0.9% NaCl or D5W is stable for 8 hr at room temperature and solution diluted with 0.9% NaCl is stable for 12 hr if refrigerated. Administration must be completed during this time. Solution is clear and colorless; do not administer solutions that are discolored or contain a precipitate.
• Rate: Administer via central venous catheter over 2 hr every 6 hr for 4 days for a total of 16 doses. Use infusion pump to administer entire dose over 2 hr.
• Y-Site Compatibility:
  • acyclovir
  • amiodarone
  • amphotericin B lipid complex
  • amphotericin B liposomal
  • anidulafungin
  • argatroban
  • arsenic trioxide
  • bivalirudin
  • bleomycin
  • caspofungin
  • dacarbazine
  • daptomycin
  • dexmedetomidine
  • dexrazoxane
  • diltiazem
  • docetaxel
  • ertapenem
  • foscarnet
  • fosphenytoin
  • granisetron
  • hetastarch
  • hydromorphone
  • leucovorin calcium
  • levofloxacin
  • linezolid
  • lorazepam
  • meperidine
  • mesna
  • metronidazole
  • milrinone
  • moxifloxacin
  • octreotide
  • ondansetron
  • paclitaxel
  • palonosetron
  • piperacillin/tazobactam
  • potassium acetate
  • rituximab
  • sodium acetate
  • tacrolimus
  • tigecycline
  • tirofiban
  • trastuzumab
  • vasopressin
  • vinblastine
  • zoledronic acid
• Y-Site Incompatibility:
  • idarubicin
  • thiotepa
  • vecuronium
  • voriconazole
.

• Instruct patient to take medication as directed, at the same time each day, even if nausea and vomiting are a problem. Consult health care professional if vomiting occurs shortly after dose is taken. If a dose is missed, do not take at all; do not double doses.
• Advise patient to notify health care professional if fever; sore throat; signs of infection; lower back or side pain; difficult or painful urination; sores in the mouth or on the lips; chills; dyspnea; persistent cough; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
• Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection occur.
• Discuss with patient the possibility of hair loss. Explore methods of coping.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Advise patient to notify health care professional if unusual bleeding; bruising; or flank, stomach, or joint pain occurs. Advise patients on long-term therapy to notify health care professional immediately if cough, shortness of breath, and fever occur or if darkening of skin, diarrhea, dizziness, fatigue, anorexia, confusion, or nausea and vomiting become pronounced.
• Inform patient of increased risk of a second malignancy with busulfan.
• May cause fetal harm. Advise female patients of reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during therapy. Advise men with female partners of reproductive potential to use effective contraception during and for 3 mo after last dose of therapy. Women need to use contraception even if amenorrhea occurs. May impair fertility in male and female patients.
• Advise patient of the importance of periodic blood counts.

• Decrease in leukocyte count to within normal limits.
  • Decreased night sweats.
  • Increase in appetite.
  • Increased sense of well-being. Therapy is resumed when leukocyte count reaches 50,000/mm³.

Busulfex, Myleran