Busulfan (3 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, TABLET.
Routes of administration: INJECTION, ORAL.
Brand Names
- BUSULFAN
- BUSULFEX
- MYLERAN
Boxed Warning
BUSULFEX (busulfan) Injection causes severe and prolonged myelosuppression at the recommended dosage. Hematopoietic progenitor cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression [see Warnings and Precautions (5.1)].
Indications and Usage
BUSULFEX is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
Contraindications
BUSULFEX is contraindicated in patients with a history of hypersensitivity to any of its components.
Adverse Reactions
The following adverse reactions are discussed in more detail in other sections of the labeling: Myelosuppression [see Warnings and Precautions (5.1)] Seizures [see Warnings and Precautions (5.2)] Hepatic Veno-Occlusive Disease (HVOD) [see Warnings and Precautions (5.3)] Embryo-fetal Toxicity [see Warnings and Precautions (5.4)] Cardiac Tamponade [see Warnings and Precautions (5.5)] Bronchopulmonary Dysplasia [see Warnings and Precautions (5.6)] Cellular Dysplasia [see Warnings and Precautions (5.7)]
Mechanism of Action
Busulfan is a bifunctional alkylating agent in which two labile methanesulfonate groups are attached to opposite ends of a four-carbon alkyl chain. In aqueous media, busulfan hydrolyzes to release the methanesulfonate groups. This produces reactive carbonium ions that can alkylate DNA. DNA damage is thought to be responsible for much of the cytotoxicity of busulfan.
Overdosage
There is no known antidote to BUSULFEX other than hematopoietic progenitor cell transplantation. In the absence of hematopoietic progenitor cell transplantation, the recommended dosage for BUSULFEX would constitute an overdose of busulfan. The principal toxic effect is profound bone marrow hypoplasia/aplasia and pancytopenia, but the central nervous system, liver, lungs, and gastrointestinal tract may be affected. Monitor hematologic status closely and institute vigorous supportive measures as medically indicated. Survival after a single 140 mg dose of Myleran® tablets in an 18 kg, 4-year-old child has been reported. Inadvertent administration of a greater than normal dose of oral busulfan (2.1 mg per kg; total dose of 23.3 mg per kg) occurred in a 2-year-old child prior to a scheduled bone marrow transplant without sequelae. An acute dose of 2.4 g was fatal in a 10-year-old boy. There is one report that busulfan is dialyzable, thus dialysis should be considered in the case of overdose.