Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. This conjugate undergoes further extensive oxidative metabolism in the liver.^1,2

Acetaminophen¹

• Not recommended prior to (<72 hours) or concurrent with IV BUSULFEX infusion
• Usage decreases glutathione levels in blood and tissues and therefore may reduce busulfan clearance

Itraconazole^1,3

• Decreases busulfan clearance by up to 25%, and may produce an AUC >1500 µMol•min in some patients

Metronidazole

• Significantly increases plasma levels of busulfan, which may lead to treatment-related toxicity⁴

Antiemetics¹

• Have no apparent effect on dosing

Phenytoin

• Should be initiated prior to IV BUSULFEX therapy¹
• Increases clearance of busulfan by 15% or more, possibly due to induction of glutathione S-transferase. Since PK of IV BUSULFEX were studied in patients treated with phenytoin, clearance of IV BUSULFEX at the recommended dose may be lower and exposure (AUC) higher in patients not treated with phenytoin^1,5

Lorazepam

• In a retrospective review, 29 pediatric patients (ages 6 months to 19 years) who received lorazepam for seizure prophylaxis did not develop seizures while receiving or within 48 hours of last dose of IV BUSULFEX⁶
• During high dose IV BUSULFEX treatment, PK data showed no alteration in absorption and clearance of busulfan during concomitant administration of lorazepam⁶

1. Prescribing Information for IV BUSULFEX.
2. Czerwinski M, Gibbs JP, Slattery JT. Busulfan conjugation by glutathione S-transferases α, µ, and π. Drug Metab Dispos. 1996;24:1015-1019.
3. Buggia I, Zecca M, Paolo E, et al. Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. Anticancer Res. 1996;16:2083-2088.
4. Nilsson C, Aschan J, Hentschke P, et al. The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;31:429-435.
5. Hassan M, Öberg G, Björkholm M, et al. Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics. Cancer Chemother Pharmacol. 1993;33:181-186.
6. Chan KW, Mullen CA, Worth LL, et al. Lorazepam for seizure prophylaxis during high-dose busulfan administration. Bone Marrow Transplant. 2002;29:963-965.

The only FDA-approved agent for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia (CML)

Important Safety Information At the recommended dosage, IV BUSULFEX^® (busulfan) produced profound myelosuppression in all patients (ie, severe granulocytopenia, thrombocytopenia, anemia, or a combination thereof). Frequent complete blood counts should be monitored during treatment and until recovery. Hepatic veno-occlusive disease was diagnosed in 5/61 patients and was fatal in 2/5 cases. Anticonvulsant prophylactic therapy should be administered prior to treatment. Caution should be exercised in patients with a history of seizure disorder or head trauma or who are receiving other potentially epileptogenic drugs. Bronchopulmonary dysplasia with pulmonary fibrosis is a rare but serious condition following chronic busulfan therapy. Women of childbearing potential should be advised to avoid becoming pregnant as busulfan may cause fetal harm.

The most common nonhematologic adverse events were nausea (92% mild or moderate, 7% severe), stomatitis (71% grade 1-2, 26% grade 3-4), and vomiting (95% mild or moderate), anorexia (64% mild or moderate, 21% severe), diarrhea (75% mild or moderate, 5% grade 3-4), insomnia (83% mild or moderate, 1% severe), and fever (78% mild or moderate, 3% life-threatening).

Please see Full Prescribing Information.