Oral levetiracetam for prevention of busulfan-induced seizures in adult hematopoietic cell transplant

Chaguaceda, Cristian; Aguilera-Jiménez, Verónica; Gutiérrez, Gonzalo; Roura, Judit; Riu, Gisela

doi:10.1007/s11096-020-00977-7

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…Other studies on adult patients also reported no seizure when LEV was administrated about 12 h before Bu. 14,16,20 Loading doses of AEDs are recommended to be avoided except for emergency treatment since overtreatment with antiepileptic agents can lead to serious adverse effects without additional benefits. 24 So giving a loading dose of LEV just when there is not enough time to reach a steady state during the highest seizure risk of Bu period is reasonable.…”

Section: Discussionmentioning

confidence: 99%

Optimal regimen of levetiracetam for prevention of busulfan-induced seizure in patients undergoing hematopoietic stem cell transplantation: A review of available evidence

Tavajohi

Shahrami

Rostami

et al. 2023

J Oncol Pharm Pract

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Objective This review aimed to summarize the available data and offer a practical recommendation regarding the optimal regimen of levetiracetam (LEV) for the prevention of busulfan-induced seizure (BIS) in patients undergoing hematopoietic stem cell transplantation (HSCT). Data Sources Published articles by searching databases (PubMed, Google Scholar, Cochrane Library, ScienceDirect) were reviewed. All types of original studies performed in pediatric and adult populations have been investigated and required data was extracted. Data Summary Eleven articles were eligible to be included in this review. A loading dose was not used in any of the studies. LEV had been started from 6 to 48 h before busulfan (Bu) initiation and continued up to 24 to 48 h after its termination. The dose range of LEV was 10 to 20 mg/kg/day divided every 12 h in pediatrics and 500 to 1000 mg twice daily in adults. Both oral and intravenous (IV) routes of administration were used. Except for three studies, no seizure had occurred in patients who had received LEV. Conclusions Considering the available evidence, LEV with the dose range from 500 to 1000 mg twice daily in adults and 10 mg/kg twice daily (20 mg/kg/day in 2 divided doses) in children orally or IV started from 6 to 24 h before Bu initiation up to 24 to 48 h after the last dose of Bu seems to prevent BIS appropriately. More prospective clinical trials with a larger population are needed to validate the optimal dosing of LEV for BIS prophylaxis in patients undergoing HSCT.

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Section: Discussionmentioning

confidence: 99%

Optimal regimen of levetiracetam for prevention of busulfan-induced seizure in patients undergoing hematopoietic stem cell transplantation: A review of available evidence

Tavajohi

Shahrami

Rostami

et al. 2023

J Oncol Pharm Pract

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“…Moreover, if levetiracetam increased the hepatic clearance of Bu, such an effect would also be expected when Bu is administered intravenously. However, despite the widespread use of the combination of intravenous Bu and levetiracetam, such an interaction has not been reported, 6,8,15,16 although these studies focused primarily on the safety and efficacy of levetiracetam during conditioning rather than Bu PK. In particular, 1 study 15 found no significant difference between the expected and recommended dosages of IV Bu needed to achieve the target AUC with levetiracetam comedication, suggesting that levetiracetam did not have a significant effect on the PK of Bu.…”

Section: Discussionmentioning

confidence: 99%

“…Phenytoin has traditionally been used in adults, but in view of its significant adverse effects and potential drug-drug interactions, 5 it has been increasingly replaced by levetiracetam for antiseizure prophylaxis, with comparable efficacy. [6][7][8] Accordingly, in August 2019, oral levetiracetam became the standard antiepileptic prophylaxis used during Bu-based conditioning in our adult HSCT department. We have since observed an increasing number of patients with delayed Bu absorption and low exposure (measured as area under the Bu concentration over time curve during the 6-hour dosing interval, AUC 0-6 ), requiring substantial increases in Bu doses to reach target exposure.…”

Section: Introductionmentioning

confidence: 99%

Decreased Systemic Busulfan Exposure After Oral Dosing With Concomitant Levetiracetam Compared With Phenytoin

Artul

Henig

Nassar

et al. 2022

Therapeutic Drug Monitoring

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Background: Busulfan (Bu) conditioning used in hematopoietic stem cell transplantation may induce seizures, and prophylactic antiepileptic treatment is recommended. Following updated guidelines, in August 2019, the adult hematopoietic stem cell transplantation department of the Rambam Health Care Campus (Haifa, Israel) switched the antiepileptic prophylaxis protocol from phenytoin to oral levetiracetam during oral Bu conditioning. The aim of this study was to compare the pharmacokinetic parameters of Bu after oral dosing between patients receiving phenytoin and those receiving levetiracetam prophylaxis.Methods: This study was a retrospective cohort study in adults undergoing myoablative conditioning with oral Bu between August 2018 and August 2020. Bu pharmacokinetic parameters (AUC 0-6 , C 0 , C max , and T max ) were compared in patients treated with phenytoin comedication (during the year before the change in policy) and levetiracetam comedication (during the year after the change). Potential confounders were accounted for including age, azole comedication, and body weight.Results: There were no significant differences in demographic and clinical parameters or weight-corrected Bu dose between the phenytoin group (n = 28) and the levetiracetam group (n = 25). There was no difference in the rate of voriconazole comedication, but fluconazole was more common in the phenytoin group (P = 0.026). The median AUC 0-6 was significantly lower in the levetiracetam group (949 mM*min; IQR = 806 to 1101 mM*min) than in the phenytoin group (1208 mM*min; IQR = 1087 to 1389 mM*min; P , 0.001). This is a clinically significant difference of 258 mM*min (21%). Azole use was not associated with Bu exposure. Conclusions:The findings suggest that, after treatment with oral Bu, oral levetiracetam comedication is associated with reduced systemic exposure compared with phenytoin comedication, possibly because of decreased bioavailability.

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“…Patients receiving busulfan who were considered high risk according to the EMBT handbook were given defibrotide prophylaxis intravenously with a dose of 6.25 mg/kg every 6 h, as suggested by the FDA 6,7 . In our unit, concurrent clonazepam was administered with busulfan for seizure prevention as neurotoxicity prophylaxis is recommended by various studies 8 . Anti‐epileptics were not administered with treosulfan as it is considered a safer drug in terms of the neurotoxicity profile.…”

Section: Methodsmentioning

confidence: 99%

Treosulfan is a safe and effective alternative to busulfan for conditioning in adult allogeneic HSCT patients: Data from a single center

Uzay,

Gündoğdu,

Koşan

et al. 2024

Cancer Medicine

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IntroductionType of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post‐transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution.MethodsTreosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non‐relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed.ResultsThe median follow‐up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non‐relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962).ConclusionTreosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.

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Oral levetiracetam for prevention of busulfan-induced seizures in adult hematopoietic cell transplant

Cited by 8 publications

References 8 publications

Optimal regimen of levetiracetam for prevention of busulfan-induced seizure in patients undergoing hematopoietic stem cell transplantation: A review of available evidence

Optimal regimen of levetiracetam for prevention of busulfan-induced seizure in patients undergoing hematopoietic stem cell transplantation: A review of available evidence

Decreased Systemic Busulfan Exposure After Oral Dosing With Concomitant Levetiracetam Compared With Phenytoin

Treosulfan is a safe and effective alternative to busulfan for conditioning in adult allogeneic HSCT patients: Data from a single center

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