Busulfex

Busilvex (UK), Busulfex, Myleran

busulfan

(byoo-sul-fan) ,

Busulfex

(trade name),

Myleran

(trade name) Pregnancy Category: D

Indications

Action

Pharmacokinetics

Time/action profile (effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 wk	weeks	up to 1 mo†
IV	unknown	unknown	13 days‡

†Complete recovery may take up to 20 mo‡After administration of last dose

Contraindications/Precautions

Adverse Reactions/Side Effects

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

Central nervous system

IV:
• seizures (life-threatening)
• cerebral hemorrhage/coma (life-threatening)
• anxiety (most frequent)
• confusion (most frequent)
• depression (most frequent)
• dizziness (most frequent)
• headache (most frequent)
• encephalopathy
• mental status changes
• weakness (most frequent)

Ear, Eye, Nose, Throat

PO:
• cataracts
IV:
• epistaxis (most frequent)
• pharyngitis (most frequent)
• ear disorders

Cardiovascular

• hepatic veno-oclusive disease (↑ allogenic transplantation)

Respiratory

PO:
• pulmonary fibrosis (life-threatening)
IV:
• alveolar hemorrhage
• asthma
• atelectasis
• cough
• hemoptysis
• hypoxia
• pleural effusion
• pneumonia
• rhinitis
• sinusitis

Cardiovascular

PO:
• cardiac tamponade (with high-dose cyclophosphamide) (life-threatening)
IV:
• chest pain (most frequent)
• hypotension (most frequent)
• tachycardia (most frequent)
• thrombosis (most frequent)
• arrhythmias
• atrial fibrillation
• cardiomegaly
• ECG changes
• edema
• heart block
• heart failure
• hypertension
• pericardial effusion
• ventricular extrasystoles

Gastrointestinal

PO:
• drug-induced hepatitis
• nausea
• vomiting
IV:
• abdominal enlargement (most frequent)
• anorexia (most frequent)
• constipation (most frequent)
• diarrhea (most frequent)
• dry mouth (most frequent)
• hematemesis (most frequent)
• nausea (most frequent)
• rectal discomfort (most frequent)
• vomiting (most frequent)
• abdominal pain
• dyspepsia
• hepatomegaly
• pancreatitis
• stomatitis

Genitourinary

• oliguria (most frequent)
• dysuria
• hematuria

Dermatologic

PO:
• itching (most frequent)
• rashes (most frequent)
• acne
• alopecia
• erythema nodosum
• exfoliative dermatitis
• hyperpigmentation

Endocrinologic

PO:
• sterility (most frequent)
• gynecomastia

Fluid and Electrolyte

• hypokalemia (most frequent)
• hypomagnesemia (most frequent)
• hypophosphatemia (most frequent)

Hematologic

• bone marrow depression (life-threatening)

Local

• inflammation/pain at injection site (most frequent)

Metabolic

PO and IV:
• hyperuricemia
IV:
• hyperglycemia (most frequent)

Musculoskeletal

• arthralgia (most frequent)
• myalgia (most frequent)
• back pain

Miscellaneous

• allergic reactions (most frequent)
• chills (most frequent)
• fever (most frequent)
• infection (most frequent)

Interactions

Drug-Drug interaction

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.Concurrent use with itraconazole or phenytoin ↓ blood level 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.

Route/Dosage

Many other regimens are used. See current protocols for up-to-date dosage

Availability

Nursing implications

Nursing assessment

• 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.
• Intravenous: Premedicate patient with phenytoin before IV administration to minimize the risk of seizures.
  • Administer antiemetics before IV administration and on a fixed schedule throughout IV administration.
• Lab Test Considerations: 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.

Potential Nursing Diagnoses

Disturbed body image (Side Effects)
Risk for injury (Side Effects)
Risk for infection (Side Effects)

Implementation

• 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 Alkeran or Leukeran.
• Oral: Administer at the same time each day. Administer on an empty stomach to decrease nausea and vomiting.

• Intravenous Administration

• pH: 3.4–3.9.
• Intravenous: Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
• Intermittent Infusion: Diluent: Dilute with 10 times the volume of busulfan using 0.9% NaCl or D5W.Concentration: ≥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. 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, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, bivalirudin, bleomycin, caspofungin, daptomycin, dexmedetomidine, diltiazem, docetaxel, ertapenem, fenoldopam, granisetron, hetastarch, hydromorphone, levofloxacin, linezolid, lorazepam, meperidine, metronidazole, milrinone, nesiritide, octreotide, ondansetron, paclitaxel, palonosetron, pancuronium, piperacillin/tazobactam, potassium acetate, quinupristin/dalfopristin, rituximab, sodium acetate, tacrolimus, tigecycline, tirofiban, trastuzumab, vasopressin, zoledronic acid
• Y-Site Incompatibility: idarubicin, thiotepa, vecuronium, voriconazole

Patient/Family Teaching

• 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.
• Review with patient the need for contraception during therapy. Women need to use contraception even if amenorrhea occurs.

Evaluation/Desired Outcomes

• 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.