busulfan

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

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;
Rep: 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.

Adv. Reactions/Side Effects ⬆ ⬇

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

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

Derm: POitching, rash, acne, alopecia, erythema nodosum, exfoliative dermatitis, hyperpigmentation

EENT: POcataracts, IVepistaxis, pharyngitis, ear disorders

Endo: PO and IVhyperuricemia, IVhyperglycemia, POsterility, gynecomastia

F and E: hypokalemia, hypomagnesemia, hypophosphatemia

GI: POdrug-induced hepatitis, nausea, vomiting, IVabdominal 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, ↓fertility, dysuria, hematuria

Hemat: MYELOSUPPRESSION

Local: inflammation/pain at injection site

MS: arthralgia, myalgia, back pain

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

Resp: POPULMONARY FIBROSIS, IValveolar hemorrhage, asthma, atelectasis, cough, hemoptysis, hypoxia, pleural effusion, pneumonia, rhinitis, sinusitis

Misc: allergic reactions, chills, fever, infection

Interactions ⬆ ⬇

Drug-drug:

Concurrent or previous (within 72 hr) use of acetaminophen may ↑ levels and risk of 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.

Route/Dosage ⬆ ⬇

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.

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

High Alert:
Monitor for myelosuppression. Assess for bleeding (bleeding gums; bruising; petechiae; guaiac stools, urine, or emesis) and avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for ≥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 fatigue, dyspnea, and orthostatic hypotension. Notify health care professional if these symptoms occur.
Monitor for significant changes in intake/output and daily weights.
- Monitor for symptoms of gout (↑ uric acid, joint pain, lower back or side pain, swelling of feet or lower legs). Encourage patient to drink ≥2 L of fluid each day. Allopurinol may be given to ↓ uric acid levels. Alkalinization of urine may be ordered to ↑ 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.

Lab Test Considerations:

Monitor CBC with differential 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. If WBC <15,000/mm³ or if a precipitous drop occurs, treat as per guidelines. If platelet count <150,000/mm³, institute thrombocytopenia precautions. Myelosuppression 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 ↑ uric acid levels.
- May cause false-positive cytology results of breast, bladder, cervix, and lung tissues.

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.
IV: Premedicate patient with phenytoin before IV administration to minimize seizure risk.
- Administer antiemetics before and on a fixed schedule during IV administration.
PO: Administer at the same time each day on an empty stomach to ↓ 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: Diluent: Use needle with 5-micron nylon filter provided to remove calculated volume of busulfan from vial; remove and replace needle, and inject busulfan into diluent. Do not use polycarbonate syringe. Add 9.3 mL busulfan to 93 mL 0.9% NaCl or D5W. Mix by inverting several times. 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 solution if discolored or contains precipitates.Concentration: 0.5 mg/mL.
Rate: Administer via central venous catheter over 2 hr every 6 hr for 4 days for a total of 16 doses. Before and after infusion, flush catheter with 5 mL 0.9% NaCl or D5W.
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
- levofloxacin
- linezolid
- lorazepam
- meperidine
- mesna
- methadone
- 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

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed, at the same time each day. Consult health care professional if vomiting occurs shortly after dose is taken. If dose is missed, omit; 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 mouth or on lips; chills; dyspnea; persistent cough; bleeding gums; easy bleeding, 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 patients on long-term therapy to notify health care professional immediately if cough, shortness of breath, fever, or joint pain occur or if darkening of skin, diarrhea, dizziness, fatigue, anorexia, confusion, or nausea and vomiting become pronounced.
Inform patient of ↑ risk of a second malignancy with busulfan.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy 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. May impair fertility.
Advise patient of the importance of periodic blood counts.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇