Comparison of levetiracetam with phenytoin for the prevention of intravenous busulfan-induced seizures in hematopoietic cell transplantation recipients

Abstract

PurposeBusulfan is used as a conditioning regimen for hematopoietic stem cell transplantation and is known to cause seizures as a side effect. As various anticonvulsant drugs have been reported, we conducted a retrospective investigation regarding the preventive effects and adverse events associated with different anticonvulsants administered alongside intravenous busulfan (ivBu) in our institution.MethodsWe targeted 104 patients who received ivBu at our institution from May 1, 2010 to April 30, 2017. We investigated the seizure prevention rate and adverse events rate under anticonvulsant prophylaxis.ResultsThere were 70 cases (67.3%) of phenytoin administration and 34 cases (32.7%) of levetiracetam administration for anticonvulsant therapy. The seizure prevention rate was 98.6% for phenytoin and 100% for levetiracetam; seizures occurred in one out of 104 patients. There were no significant differences in the seizure prevention rate depending on the type of anticonvulsant. Further, there were no differences in adverse events.ConclusionsAnticonvulsant prophylaxis is considered necessary for safe conditioning with ivBu. Adverse events associated with the use of levetiracetam are within an acceptable range. Further, levetiracetam is considered useful as a preventive drug against seizures during ivBu administration because it is easy to administer and has ideal pharmacokinetics for supportive care.

Comparison of levetiracetam versus phenytoin/fosphenytoin for busulfan seizure prophylaxis at a pediatric institution

“…Busulfan-induced seizures were first reported in 1984 by Marcus et al 8 Studies have shown that busulfan-induced seizures occur at a frequency of 1-40% in patients without any anticonvulsant prophylaxis and breakthrough seizure rates of 0-15% in patients who are treated with prophylactic anticonvulsant therapy. 2,[9][10][11] The overall seizure prevention rate in our study was 98.5% therefore similar to the incidence reported throughout the literature. 1,7 Our results are in keeping with Akiyama et al, who found a seizure prevention rate of 98.6% with phenytoin and 100% for levetiracetam and concluded there was no difference in seizure breakthrough rate or adverse effects in an adult population.…”

“…Similar to other studies comparing phenytoin and levetiracetam for busulfan seizure prophylaxis, we did not find any difference in the occurrence of oral mucositis any grade or veno‐occlusive disease 1,7,9 …”

“…Busulfan‐induced seizures were first reported in 1984 by Marcus et al 8 Studies have shown that busulfan‐induced seizures occur at a frequency of 1–40% in patients without any anticonvulsant prophylaxis and breakthrough seizure rates of 0–15% in patients who are treated with prophylactic anticonvulsant therapy 2,9‐11 . The overall seizure prevention rate in our study was 98.5% therefore similar to the incidence reported throughout the literature 1,7 …”

“…Similar to other studies comparing phenytoin and levetiracetam for busulfan seizure prophylaxis, we did not find any difference in the occurrence of oral mucositis any grade or veno-occlusive disease. 1,7,9 Limitations of our study include it is a retrospective study at a single pediatric institution. Also, given the 9-year study period, we could not control for changes in the standard of practice for GVHD prophylaxis or other supportive care that may have occurred.…”

“…1,7 Our results are in keeping with Akiyama et al, who found a seizure prevention rate of 98.6% with phenytoin and 100% for levetiracetam and concluded there was no difference in seizure breakthrough rate or adverse effects in an adult population. 9 Similarly, Soni et al evaluated 53 children and young adults who had received levetiracetam or phenytoin for seizure prophylaxis prior to busulfan administration. This study found no breakthrough seizure with levetiracetam and 1 breakthrough seizure with phenytoin.…”