Busulfan

What it is and how it works

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.

Mechanism class: Alkylating Activity

Indications

Busulfan injection is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. Busulfan injection is an alkylating drug indicated for: Use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia (CML)

Dosage and administration (summary)

Pre-medicate with anticonvulsants (e.g. benzodiazepines, phenytoin, valproic acid or levetiracetam) and antiemetic ( 2.1 , 5.2 ) Dilute and administer as intravenous infusion. Do not administer as intravenous push or bolus ( 2.1 , 2.3 ) Recommended adult dose: 0.8 mg per kg of ideal body weight or actual body weight, whichever is lower, administered intravenously via a central venous catheter as a two-hour infusion every six hours for four consecutive days for a total of 16 doses Initial Dosing Information • Administer busulfan injection in combination with cyclophosphamide as a conditioning regimen prior to bone marrow or peripheral blood progenitor cell replacement.

Contraindications

Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components. Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components

Warnings and precautions

Seizures: Initiate anticonvulsant prophylactic therapy prior to treatment with busulfan. Monitor patients with history of seizure disorder, head trauma or receiving epileptogenic drugs Hepatic Veno-Occlusive Disease (HVOD): Increased risk of developing HVOD at AUC greater than 1,500 µM·min. Monitor serum transaminases, alkaline phosphatase and bilirubin daily Embryo-fetal Toxicity: Can cause fetal harm.

Pregnancy

Pregnancy Risk Summary Busulfan can cause fetal harm when administered to a pregnant woman based on animal data. Busulfan was teratogenic in mice, rats, and rabbits following administration during organogenesis. The solvent, DMA, may also cause fetal harm when administered to a pregnant woman.

Storage and supply

How Supplied Busulfan injection is packaged as a clear, colorless, sterile solution in 10 mL single-dose clear glass vials. 60 mg per 10 mL (6 mg/mL) 10 mL Single-Dose Vials Packaged in a Carton of 8 NDC 55150-395-08 Storage and Handling Unopened vials of busulfan injection must be stored under refrigerated conditions between 2°C to 8°C (36°F to 46…

Source: Busulfan (Busulfan) — US FDA prescribing information, 2024-06-27, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.