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Hideo Yasunaga - One of the best experts on this subject based on the ideXlab platform.
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phenytoin versus Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Seizure-european Journal of Epilepsy, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Kiyohide Fushimi, Hiromu Naraba, Hidehiko Nakano, Hideo YasunagaAbstract:Abstract Purpose For status epilepticus, the choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial: phenytoin or Fosphenytoin are recommended, however, it has been unknown which is better. Using a nationwide database, we compared the efficacy and safety of them. Method An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from January 1, 2011 through December 31, 2015. Propensity score matching was applied to compare outcomes of the phenytoin and Fosphenytoin groups. Results The analysis examined data of 5265 patients: 2969 patients received phenytoin; 2296 received Fosphenytoin, on the day of admission. One-to-one propensity score matching created 1871 matched pairs. No significant difference was found for vasopressor use on the day of admission (4.2 % vs. 4.4 %; odds ratio 1.07; 95 % confidence intervals 0.77–1.48; p = 0.69), or for mechanical ventilation on the day of admission, in-hospital mortality, length of hospital stay, or total hospitalization cost. Higher age, comorbidity of cardiac diseases and lower body mass index were associated significantly with increased vasopressor use, whereas the dose of phenytoin equivalents and the choice of Fosphenytoin were not. Conclusions This nationwide observational study found no evidence that Fosphenytoin provides higher efficacy or safety than phenytoin for treatment of status epilepticus in adults after diazepam. Age, cardiac disease and low body mass index were identified as independent risk factors for vasopressor use in both phenytoin and Fosphenytoin.
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levetiracetam vs Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Frontiers in Neurology, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Aiki Marushima, Yoshiaki Inoue, Kiyohide Fushimi, Hideo YasunagaAbstract:OBJECTIVE: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam versus Fosphenytoin. We compare the safety of intravenous levetiracetam and Fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. METHODS: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous Fosphenytoin on the day of admission were defined as the Fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and Fosphenytoin groups. RESULTS: The analysis examined data of 5667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received Fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2% vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73–1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the Fosphenytoin group (3.2% vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43–0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. CONCLUSION: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for Fosphenytoin, in adult status epilepticus.
Kensuke Nakamura - One of the best experts on this subject based on the ideXlab platform.
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phenytoin versus Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Seizure-european Journal of Epilepsy, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Kiyohide Fushimi, Hiromu Naraba, Hidehiko Nakano, Hideo YasunagaAbstract:Abstract Purpose For status epilepticus, the choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial: phenytoin or Fosphenytoin are recommended, however, it has been unknown which is better. Using a nationwide database, we compared the efficacy and safety of them. Method An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from January 1, 2011 through December 31, 2015. Propensity score matching was applied to compare outcomes of the phenytoin and Fosphenytoin groups. Results The analysis examined data of 5265 patients: 2969 patients received phenytoin; 2296 received Fosphenytoin, on the day of admission. One-to-one propensity score matching created 1871 matched pairs. No significant difference was found for vasopressor use on the day of admission (4.2 % vs. 4.4 %; odds ratio 1.07; 95 % confidence intervals 0.77–1.48; p = 0.69), or for mechanical ventilation on the day of admission, in-hospital mortality, length of hospital stay, or total hospitalization cost. Higher age, comorbidity of cardiac diseases and lower body mass index were associated significantly with increased vasopressor use, whereas the dose of phenytoin equivalents and the choice of Fosphenytoin were not. Conclusions This nationwide observational study found no evidence that Fosphenytoin provides higher efficacy or safety than phenytoin for treatment of status epilepticus in adults after diazepam. Age, cardiac disease and low body mass index were identified as independent risk factors for vasopressor use in both phenytoin and Fosphenytoin.
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levetiracetam vs Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Frontiers in Neurology, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Aiki Marushima, Yoshiaki Inoue, Kiyohide Fushimi, Hideo YasunagaAbstract:OBJECTIVE: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam versus Fosphenytoin. We compare the safety of intravenous levetiracetam and Fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. METHODS: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous Fosphenytoin on the day of admission were defined as the Fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and Fosphenytoin groups. RESULTS: The analysis examined data of 5667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received Fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2% vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73–1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the Fosphenytoin group (3.2% vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43–0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. CONCLUSION: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for Fosphenytoin, in adult status epilepticus.
Simo N Muchohi - One of the best experts on this subject based on the ideXlab platform.
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Fosphenytoin for seizure prevention in childhood coma in africa a randomized clinical trial
Journal of Critical Care, 2013Co-Authors: Sa Gwe, Ri Idro, Em Chengo, Gregory Fega, Ayub Mpoya, Esthe Kivaya, Jane Crawley, Simo N MuchohiAbstract:Purpose We conducted a double-blind trial to determine whether a single intramuscular injection of Fosphenytoin prevents seizures and neurologic sequelae in children with acute coma.
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pharmacokinetics and clinical effects of phenytoin and Fosphenytoin in children with severe malaria and status epilepticus
British Journal of Clinical Pharmacology, 2003Co-Authors: Simo N Muchohi, W M Watkins, G Edwards, Ernhards Ogutu, Charles R Newto, G O Otieno, G O KokwaroAbstract:Aims Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water-soluble prodrug, Fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and Fosphenytoin sodium in children with severe falciparum malaria and status epilepticus. Methods Children received intravenous (i.v.) phenytoin as a 18 mg kg−1 loading dose infused over 20 min followed by a 2.5 mg kg−1 12 hourly maintenance dose infused over 5 min (n = 11), or i.v. Fosphenytoin, administered at a rate of 50 mg min−1 phenytoin sodium equivalents (PE; n = 16), or intramuscular (i.m.) Fosphenytoin as a 18 mg kg−1 loading dose followed by 2.5 mg kg−1 12 hourly of PE (n = 11). Concentrations of phenytoin in plasma and cerebrospinal fluid (CSF), frequency of seizures, cardiovascular effects (respiratory rate, blood pressure, trancutaneous oxygen tension and level of consciousness) and middle cerebral artery (MCA) blood flow velocity were monitored. Results After all routes of administration, a plasma unbound phenytoin concentration of more than 1 µg ml−1 was rapidly (within 5–20 min) attained. Mean (95% confidence interval) steady state free phenytoin concentrations were 2.1 (1.7, 2.4; i.v. phenytoin, n = 6), 1.5 (0.96, 2.1; i.v. Fosphenytoin, n = 11) and 1.4 (0.5, 2.4; i.m. Fosphenytoin, n = 6), and were not statistically different for the three routes of administration. Median times (range) to peak plasma phenytoin concentrations following the loading dose were 0.08 (0.08–0.17), 0.37 (0.33–0.67) and 0.38 (0.17–2.0) h for i.v. Fosphenytoin, i.v. phenytoin and i.m. Fosphenytoin, respectively. CSF: plasma phenytoin concentration ratio ranged from 0.12 to 0.53 (median = 0.28, n = 16). Status epilepticus was controlled in only 36% (4/11) following i.v. phenytoin, 44% (7/16), following i.v. Fosphenytoin and 64% (7/11) following i.m. Fosphenytoin administration, respectively. Cardiovascular parameters and MCA blood flow were not affected by phenytoin administration. Conclusions Phenytoin and Fosphenytoin administration at the currently recommended doses achieve plasma unbound phenytoin concentrations within the therapeutic range with few cardiovascular effects. Administration of Fosphenytoin i.v. or i.m. offers a practical and convenient alternative to i.v. phenytoin. However, the inadequate control of status epilepticus despite rapid achievement of therapeutic unbound phenytoin concentrations warrants further investigation.
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phenytoin pharmacokinetics and clinical effects in african children following Fosphenytoin and chloramphenicol coadministration
British Journal of Clinical Pharmacology, 2002Co-Authors: Ernhards Ogutu, Simo N Muchohi, Charles R Newto, G O Otieno, G O KokwaroAbstract:Aims Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for convulsions. Since chloramphenicol inhibits the metabolism of phenytoin in vivo, we studied the effects of chloramphenicol on phenytoin pharmacokinetics in children with malaria. Methods Multiple intravenous (i.v.) doses of chloramphenicol succinate (CAP) (25 mg kg-1 6 hourly for 72 h) and a single intramuscular (i.m.) seizure prophylactic dose of Fosphenytoin (18 mg kg-1 phenytoin sodium equivalents) were concomitantly administered to 15 African children with malaria. Control children (n = 13) with malaria received a similar dose of Fosphenytoin and multiple i.v. doses (25 mg kg-1 8 hourly for 72 h) of cefotaxime (CEF). Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness and convulsion episodes were monitored. Cerebrospinal fluid (CSF) and plasma phenytoin concentrations were determined. Results The area under the plasma unbound phenytoin concentration-time curve (AUC(0, infinity ); means (CAP, CEF): 58.5, 47.6 micro g ml-1 h; 95% CI for difference between means: -35.0, 11.4), the peak unbound phenytoin concentrations (Cmax; medians: 1.12, 1.29 micro g ml-1; 95% CI: -0.5, 0.04), the times to Cmax (tmax; medians: 4.0, 4.0 h; 95% CI: -2.0, 3.7), the CSF:plasma phenytoin ratios (means: 0.21, 0.22; 95% CI: -0.8, 0.10), the fraction of phenytoin unbound (means: 0.06, 0.09; 95% CI: -0.01, 0.07) and the cardiovascular parameters were not significantly different between CAP and CEF groups. However, mean terminal elimination half-life (t1/2,z) was significantly longer (23.7, 15.5 h; 95% CI: 1.71, 14.98) in the CAP group compared with the CEF group. Seventy per cent of the children had no convulsions during the study period. Conclusions Concomitant administration of chloramphenicol and a single i.m. dose of Fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria. Moreover, a single i.m. dose of Fosphenytoin provides anticonvulsant prophylaxis in the majority of the children over 72 h. However, a larger study would be needed to investigate the effect of concomitant administration of multiple doses of the two drugs in this population of patients.
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pharmacokinetics of phenytoin following intravenous and intramuscular administration of Fosphenytoin and phenytoin sodium in the rabbit
European Journal of Drug Metabolism and Pharmacokinetics, 2002Co-Authors: Simo N Muchohi, G O Kokwaro, T E Maitho, R W Munenge, W M Watkins, G EdwardsAbstract:The purpose of this study was to evaluate and compare plasma phenytoin concentration versus time profiles following intravenous (i.v) and intramuscular (i.m) administration of Fosphenytoin sodium with those obtained following administration of standard phenytoin sodium injection in the rabbit. Twenty-four adult New Zealand White rabbits (2.1±0.4 kg) were anaesthetized with sodium pentobarbitone (30 mg/kg) followed by i.v or i.m administration of a single 10 mg/kg phenytoin sodium or Fosphenytoin sodium equivalents. Blood samples (1.5 ml) were obtained from a femoral artery cannula predose and at 1, 3, 5, 7, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 min after drug administration. Plasma was separated by centrifugation (1000 g; 5 min) and Fosphenytoin, total and free plasma phenytoin concentrations were measured using high performance liquid chromatography (HPLC). Following i.v administration of Fosphenytoin sodium plasma phenytoin concentrations were similar to those obtained following i.v administration of an equivalent dose of phenytoin sodium. Mean peak plasma phenytoin concentrations (Cmax) was 158% higher (P=0.0077) following i.m administration of Fosphenytoin sodium compared to i.m administration of phenytoin sodium. The mean area under the plasma total and free phenytoin concentration-time curve from time zero to 120 min (AUC0−120) following i.m administration was also significantly higher (P=0.0277) in Fosphenytoin treated rabbits compared to the phenytoin group. However, there was no significant difference in AUC0−180 between Fosphenytoin and phenytoin-treated rabbits following i.v administration. There was also no significant difference in the mean times to achieve peak plasma phenytoin-concentrations (Tmax) between Fosphenytoin and phenytoin-treated rabbits following i.m administration. Mean plasma albumin concentrations were comparable in both groups of animals. Fosphenytoin was rapidly converted to phenytoin both after i.v and i.m administration, with plasma Fosphenytoin concentrations declining rapidly to undetectable levels within 10 min following administration via either route. These results confirm the rapid and complete hydrolysis of Fosphenytoin to phenytoin in vivo, and the potential of the i.m route for administration of Fosphenytoin delivering phenytoin in clinical settings where i.v administration may not be feasible.
Hiroki Matsui - One of the best experts on this subject based on the ideXlab platform.
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phenytoin versus Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Seizure-european Journal of Epilepsy, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Kiyohide Fushimi, Hiromu Naraba, Hidehiko Nakano, Hideo YasunagaAbstract:Abstract Purpose For status epilepticus, the choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial: phenytoin or Fosphenytoin are recommended, however, it has been unknown which is better. Using a nationwide database, we compared the efficacy and safety of them. Method An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from January 1, 2011 through December 31, 2015. Propensity score matching was applied to compare outcomes of the phenytoin and Fosphenytoin groups. Results The analysis examined data of 5265 patients: 2969 patients received phenytoin; 2296 received Fosphenytoin, on the day of admission. One-to-one propensity score matching created 1871 matched pairs. No significant difference was found for vasopressor use on the day of admission (4.2 % vs. 4.4 %; odds ratio 1.07; 95 % confidence intervals 0.77–1.48; p = 0.69), or for mechanical ventilation on the day of admission, in-hospital mortality, length of hospital stay, or total hospitalization cost. Higher age, comorbidity of cardiac diseases and lower body mass index were associated significantly with increased vasopressor use, whereas the dose of phenytoin equivalents and the choice of Fosphenytoin were not. Conclusions This nationwide observational study found no evidence that Fosphenytoin provides higher efficacy or safety than phenytoin for treatment of status epilepticus in adults after diazepam. Age, cardiac disease and low body mass index were identified as independent risk factors for vasopressor use in both phenytoin and Fosphenytoin.
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levetiracetam vs Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Frontiers in Neurology, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Aiki Marushima, Yoshiaki Inoue, Kiyohide Fushimi, Hideo YasunagaAbstract:OBJECTIVE: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam versus Fosphenytoin. We compare the safety of intravenous levetiracetam and Fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. METHODS: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous Fosphenytoin on the day of admission were defined as the Fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and Fosphenytoin groups. RESULTS: The analysis examined data of 5667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received Fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2% vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73–1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the Fosphenytoin group (3.2% vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43–0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. CONCLUSION: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for Fosphenytoin, in adult status epilepticus.
Yuji Takahashi - One of the best experts on this subject based on the ideXlab platform.
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phenytoin versus Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Seizure-european Journal of Epilepsy, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Kiyohide Fushimi, Hiromu Naraba, Hidehiko Nakano, Hideo YasunagaAbstract:Abstract Purpose For status epilepticus, the choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial: phenytoin or Fosphenytoin are recommended, however, it has been unknown which is better. Using a nationwide database, we compared the efficacy and safety of them. Method An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from January 1, 2011 through December 31, 2015. Propensity score matching was applied to compare outcomes of the phenytoin and Fosphenytoin groups. Results The analysis examined data of 5265 patients: 2969 patients received phenytoin; 2296 received Fosphenytoin, on the day of admission. One-to-one propensity score matching created 1871 matched pairs. No significant difference was found for vasopressor use on the day of admission (4.2 % vs. 4.4 %; odds ratio 1.07; 95 % confidence intervals 0.77–1.48; p = 0.69), or for mechanical ventilation on the day of admission, in-hospital mortality, length of hospital stay, or total hospitalization cost. Higher age, comorbidity of cardiac diseases and lower body mass index were associated significantly with increased vasopressor use, whereas the dose of phenytoin equivalents and the choice of Fosphenytoin were not. Conclusions This nationwide observational study found no evidence that Fosphenytoin provides higher efficacy or safety than phenytoin for treatment of status epilepticus in adults after diazepam. Age, cardiac disease and low body mass index were identified as independent risk factors for vasopressor use in both phenytoin and Fosphenytoin.
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levetiracetam vs Fosphenytoin for second line treatment of status epilepticus propensity score matching analysis using a nationwide inpatient database
Frontiers in Neurology, 2020Co-Authors: Kensuke Nakamura, Hiroyuki Ohbe, Hiroki Matsui, Yuji Takahashi, Aiki Marushima, Yoshiaki Inoue, Kiyohide Fushimi, Hideo YasunagaAbstract:OBJECTIVE: Status epilepticus is a major emergency condition. The choice of antiepileptic drugs for second-line treatment after benzodiazepine remains controversial, including levetiracetam versus Fosphenytoin. We compare the safety of intravenous levetiracetam and Fosphenytoin as a second-line treatment in patients with status epilepticus using a nationwide database. METHODS: An observational study conducted with the Japanese Diagnosis Procedure Combination inpatient database identified adult patients who had been admitted for status epilepticus and who had received intravenous diazepam on the day of admission from March 1, 2011 to March 31, 2018. Patients who received intravenous levetiracetam on the day of admission were defined as the levetiracetam group and those who received intravenous Fosphenytoin on the day of admission were defined as the Fosphenytoin group. Propensity score matching was performed to compare outcomes obtained for the levetiracetam and Fosphenytoin groups. RESULTS: The analysis examined data of 5667 patients. Overall, 1,403 (25%) patients received levetiracetam; 4,264 (75%) received Fosphenytoin. One-to-one propensity score matching created 1,363 matched pairs. No significant difference was found in in-hospital mortality (5.2% vs. 5.1%; odds ratio, 1.03; 95% confidence interval, 0.73–1.46). The proportion of vasopressor use on the day of admission was significantly lower for the levetiracetam group than for the Fosphenytoin group (3.2% vs. 4.9%; odds ratio, 0.63; 95% confidence interval, 0.43–0.92). No significant difference was found in other secondary outcomes including total hospitalization cost. CONCLUSION: Levetiracetam was related to significantly reduced vasopressor use on the day of admission than that found for Fosphenytoin, in adult status epilepticus.