Otsuka Corporate

IV BUSULFEX® (busulfan) Injection

IV BUSULFEX¹ is the only FDA approved agent for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia (CML).

IMPORTANT SAFETY INFORMATION

WARNING: BUSULFEX^® Injection is a potent cytotoxic drug that causes profound myelosuppression at the recommended dosage. It should be administered under the supervision of a qualified physician who is experienced in allogeneic hematopoietic stem cell transplantation, the use of cancer chemotherapeutic drugs, and the management of patients with severe pancytopenia. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available. SEE "WARNINGS" SECTION FOR INFORMATION REGARDING BUSULFAN-INDUCED PANCYTOPENIA IN HUMANS.

CONTRAINDICATIONS: Patients with a history of hypersensitivity to BUSULFEX or any of its components.

Hematologic – Profound myelosuppression (i.e., severe granulocytopenia, thrombocytopenia, anemia, or a combination thereof) occurred in all patients at the recommended dosage. Frequent complete blood counts should be monitored during treatment and until recovery. Antibiotic therapy and platelet and red blood support should be used when medically indicated. Patients should be monitored for signs of local or systemic infection or bleeding.
Neurological – 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.
Hepatic – Hepatic veno-occlusive disease (HVOD) was diagnosed in 8% (5/61) patients and was fatal in 40% (2/5) cases.
Pulmonary – Bronchopulmonary dysplasia with pulmonary fibrosis is a rare but serious condition following chronic busulfan therapy.
Carcinogenicity, Mutagenicity, Impairment of Fertility – Busulfan is a mutagen and a clastogen, and a presumed human carcinogen.
Pregnancy and Nursing Mothers – Women of childbearing potential should avoid becoming pregnant as busulfan may cause fetal harm.
Drug Interactions – Itraconazole decreases busulfan clearance by up to 25%. Phenytoin increases the clearance of busulfan by 15% or more. Use of acetaminophen prior to (<72 hours) or concurrent with BUSULFEX may result in reduced busulfan clearance.

Common non-hematologic adverse events – (incidence ≥80%): 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).

¹ Please see FULL PRESCRIBING INFORMATION including Boxed WARNING for IV BUSULFEX.