Optimal prevention of seizures induced by high-dose busulfan

Andrea L. Eberly, Gail D. Anderson, Joseph S. Bubalo, Jeannine S. McCune

    Research output: Contribution to journalReview article

    49 Scopus citations

    Abstract

    High-dose busulfan is frequently used in a variety of conditioning regimens for hematopoietic cell transplantation. In this setting, busulfan has marked neurotoxicity, specifically causing seizures that generally are tonic-clonic in character. Phenytoin has been the preferred drug to treat busulfan-induced seizures, but this practice should be reexamined in light of newer antiepileptic drugs being preferentially used by neurologists. Characteristics of ideal seizure prophylaxis include lack of overlapping toxicity with the conditioning regimen, lack of interference with engraftment of donor cells, and minimal potential for pharmacokinetic drug interactions. Based on these criteria, phenytoin is suboptimal due to possible toxicities and is especially ill suited because of its ability to induce busulfan metabolism. It is postulated that this induction adversely affects efforts to update methods for targeting busulfan doses to individual patients, based on recent developments in the understanding of the pharmacogenomics of busulfan metabolism. The existing clinical data support the use of benzodiazepines, most notably clonazepam and lorazepam, to prevent busulfan-induced seizures. The second-generation antiepileptic drug levetiracetam possesses the characteristics of optimal prophylaxis for busulfan-induced seizures, and early data of its efficacy are promising, although further study is needed.

    Original languageEnglish (US)
    Pages (from-to)1502-1510
    Number of pages9
    JournalPharmacotherapy
    Volume28
    Issue number12
    DOIs
    StatePublished - Dec 2008

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    Keywords

    • Antiepileptic drugs
    • Benzodiazepines
    • Busulfan
    • Drug interactions
    • HCT
    • Hematopoietic cell transplantation
    • Phenytoin
    • Seizure prophylaxis
    • Seizures

    ASJC Scopus subject areas

    • Pharmacology (medical)

    Cite this

    Eberly, A. L., Anderson, G. D., Bubalo, J. S., & McCune, J. S. (2008). Optimal prevention of seizures induced by high-dose busulfan. Pharmacotherapy, 28(12), 1502-1510. https://doi.org/10.1592/phco.28.12.1502