Fosphenytoin 750mg/10ml solution for injection vials

BackgroundThere is significant heterogeneity related to the use of prophylactic antiseizure medications (ASM) following supratentorial craniotomy.MethodsWe conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized following supratentorial neurosurgery with no prior seizure history. The following population, intervention, comparator, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used as seizure prophylaxis in adult patients undergoing supratentorial neurosurgery? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT) be preferentially used? and (3) Should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We utilized Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate recommendations.ResultsThe initial literature search yielded 1988 articles, and 16 formed the basis of the recommendations. PICO 1: while meta-analysis of randomized controlled trials (RCTs) demonstrated a significant benefit for early seizure prevention, meta-analyses including all study designs was nonsignificant. Further, there were no differences in late seizure or mortality rates, and there was a trend toward higher adverse event rates with ASM. PICO 2: LEV was associated with significantly lower early seizure rates than PHT, and there were trends toward fewer late seizures and adverse events with LEV. PICO 3: only three studies examined the duration of ASM treatment, and there was no significant difference in seizure events between subjects treated for a short versus long duration.ConclusionsWe suggest that either prophylactic ASM or no ASM be used for seizure prophylaxis in patients undergoing supratentorial neurosurgery (conditional recommendation, low quality of evidence). If an ASM is used, we suggest LEV over PHT (conditional recommendation, very low quality of evidence) for a short duration (conditional recommendation, very low quality of evidence).

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Abstract Background There is practice heterogeneity in the use, type and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute, non-traumatic intracerebral hemorrhage (ICH). Methods We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute, non-traumatic ICH. The following Population, Intervention, Comparator and Outcome (PICO) questions were assessed: 1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures?; 2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used?; and 3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes. We utilized Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to generate recommendations. Results The initial literature search yielded 1,988 articles, and 15 formed the basis of the recommendations. PICO 1: While there was no significant impact of ASM on the outcomes of early or late seizure or mortality, meta-analyses demonstrated increased adverse events and higher relative risk of poor functional outcomes at 90 days with prophylactic ASM use. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or adverse events, though point estimates tended to favor LEV. PICO 3: Based on one decision analysis, quality-adjusted-life-years were increased with a shorter duration of ASM prophylaxis. Conclusions We suggest avoidance of prophylactic ASM in hospitalized adult patients with acute, non-traumatic ICH (weak recommendation, very low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, very low quality of evidence).

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BackgroundTo systematically review the efficacy and safety of second-line medications for status epilepticus (SE).MethodsElectronic searches were conducted in PubMed, Embase, and The Cochrane Library for randomized controlled trials of second-line medications for SE from inception to January 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Network meta-analysis was performed using R 4.2.2 software.ResultsA total of 23 randomized controlled trials were analyzed, examining the efficacy of 5 different treatment regimens: levetiracetam (LEV), phenytoin (PHT), fosphenytoin (FPHT), valproate (VPA), and phenobarbital (PHB). The results of the network meta-analysis indicated that the seizure control rate ranking was as follows: PHB (98.1%) > LEV (60.7%) > FPHT (40.3%) > PHT (33.0%) > VPA (17.8%). The surface under the cumulative ranking (SUCRA) values revealed that PHB had the highest ranking (SUCRA, 91.8%), followed by VPA (SUCRA, 69.3%), PHT (SUCRA, 56.1%), and FPHT (SUCRA, 5.9%) for the recurrence of seizures within 24 hours. Subgroup analysis revealed that PHB was most effective for seizure control in both pediatric and adult populations, VPA demonstrated superior efficacy in children across various indicators, LEV was deemed the safest option for children and elderly individuals, and VPA was identified as the safest choice for adult patients.ConclusionsPHB continues to be a prominent option for managing SE, although its safety profile warrants careful consideration. Meanwhile, both VPA and LEV offer distinctive advantages in the treatment of SE, with each demonstrating commendable safety profiles.

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