International Journal of Hematology

, Volume 109, Issue 6, pp 694–699 | Cite as

Comparison of valproate and levetiracetam for the prevention of busulfan-induced seizures in hematopoietic stem cell transplantation

  • Toshihisa Nakashima
  • Takashi TanakaEmail author
  • Keiichi Koido
  • Yukiko Nishibuchi
  • Hironobu Hashimoto
  • Ayumu Ito
  • Yoshihiro Inamoto
  • Saiko Kurosawa
  • Sung-Won Kim
  • Takahiro Fukuda
  • Hiroyuki Terakado
Original Article


Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug–drug interactions.


Busulfan Valproate Levetiracetam Hematopoietic stem cell transplantation Extended-spectrum beta-lactamase 


Author contributions

TN, TT, TF, and HT designed the study. TN and TT performed the statistical analysis. KK, YN, HH, AI, YI, SK, and SWK reviewed the results. All authors wrote and critically revised the manuscript for important intellectual content, and approved the manuscript for publication.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Toshihisa Nakashima
    • 1
  • Takashi Tanaka
    • 2
    Email author
  • Keiichi Koido
    • 1
  • Yukiko Nishibuchi
    • 1
  • Hironobu Hashimoto
    • 1
  • Ayumu Ito
    • 2
  • Yoshihiro Inamoto
    • 2
  • Saiko Kurosawa
    • 2
  • Sung-Won Kim
    • 2
  • Takahiro Fukuda
    • 2
  • Hiroyuki Terakado
    • 1
  1. 1.Department of PharmacyNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Hematopoietic Stem Cell TransplantationNational Cancer Center HospitalTokyoJapan

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