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  11. Seizure Prophylaxis And Its Impact On Busulfan Pharmacokinetics And Dosing In A Novel Timed Sequential Protocol: Md Anderson Experience

Seizure prophylaxis and its impact on busulfan pharmacokinetics and dosing in a novel timed sequential protocol: MD Anderson experience

Jitesh D Kawedia1, Victoria W Handy1, Alan L Myers1

  • 1Department of Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Transplantation and Cellular Therapy
|June 13, 2025

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View abstract on PubMed

Summary
This summary is machine-generated.

Levetiracetam is a safe alternative to phenytoin for seizure prophylaxis during busulfan (Bu) conditioning for stem cell transplants. This change avoids a significant drug-drug interaction, improving patient safety.

Area of Science:

  • Pharmacology
  • Hematology
  • Oncology

Background:

  • High-dose busulfan (Bu) is a key component of conditioning regimens for hematopoietic stem cell transplantation.
  • Busulfan exhibits significant inter-patient pharmacokinetic variability, necessitating therapeutic drug monitoring.
  • Fractionated busulfan regimens aim to reduce non-relapse mortality in vulnerable patient populations.

Purpose of the Study:

  • To investigate busulfan pharmacokinetics in a novel fractionated regimen.
  • To evaluate the impact of seizure prophylaxis agents on busulfan clearance.
  • To identify safer alternatives for seizure prophylaxis in busulfan-based conditioning.

Main Methods:

  • Analysis of busulfan plasma concentrations and clearance during a fractionated intravenous regimen.
Keywords:
Busulfanconditioning, stem cell transplantlevetiracetampharmacokinetics, drug-drug interactions

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  • Comparison of busulfan clearance with phenytoin versus levetiracetam for seizure prophylaxis.
  • Assessment of seizure prophylaxis efficacy and adverse events for both agents.

    • Main Results:

    • A significant increase in busulfan clearance (14.7%) was observed with phenytoin.
    • Replacing phenytoin with levetiracetam resulted in a substantially lower increase in busulfan clearance (4.9%).
    • Levetiracetam demonstrated comparable seizure prophylaxis efficacy and safety to phenytoin without significant drug-drug interaction.

    Conclusions:

    • A notable drug-drug interaction exists between busulfan and phenytoin.
    • Levetiracetam is a safe and effective alternative to phenytoin for seizure prophylaxis in busulfan conditioning regimens.
    • This substitution mitigates the observed drug-drug interaction, potentially improving treatment outcomes in stem cell transplantation.
    phenytoin
    seizure prophylaxis