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Erin Frazee - One of the best experts on this subject based on the ideXlab platform.
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Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction.
Neurocritical care, 2016Co-Authors: Andrea M. New, Scott D. Nei, Kianoush Kashani, Alejandro A. Rabinstein, Erin FrazeeAbstract:Background Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate Levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe Levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction.
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Levetiracetam pharmacokinetics during continuous venovenous hemofiltration and acute liver dysfunction
Neurocritical Care, 2016Co-Authors: Andrea M. New, Scott D. Nei, Kianoush Kashani, Alejandro A. Rabinstein, Erin FrazeeAbstract:Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate Levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe Levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction. This is a case report of a single patient. A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of Levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12–46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h. Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric Levetiracetam regimen.
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Levetiracetam pharmacokinetics in a patient receiving continuous venovenous hemofiltration and venoarterial extracorporeal membrane oxygenation
Pharmacotherapy, 2015Co-Authors: Scott D. Nei, Kianoush Kashani, Erica D Wittwer, Erin FrazeeAbstract:Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of Levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that Levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous Levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new-onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5-39.8 μg/ml) and trough (ranging from 13.9-18.2 μg/ml) concentrations. Elimination half-life ranged from 8.7-10.1 hours. Renal dysfunction reduces Levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial Levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.
Anthony G Marson - One of the best experts on this subject based on the ideXlab platform.
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the sanad ii study of the effectiveness and cost effectiveness of Levetiracetam zonisamide or lamotrigine for newly diagnosed focal epilepsy an open label non inferiority multicentre phase 4 randomised controlled trial
The Lancet, 2021Co-Authors: Anthony G Marson, John Paul Leach, Graeme J Sills, Girvan Burnside, Richard Appleton, D F Smith, Catrin Tudursmith, Catrin Plumpton, Dyfrig A Hughes, Paula R WilliamsonAbstract:Summary Background Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of Levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. Methods This randomised, open-label, controlled trial compared Levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, Levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both Levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), Levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, Levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), Levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to Levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83–1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both Levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08–1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started Levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319–1·458) compared with 1·222 (1·110–1·283) for Levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. Interpretation These findings do not support the use of Levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. Funding National Institute for Health Research Health Technology Assessment programme.
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Levetiracetam add on for drug resistant focal epilepsy an updated cochrane review
Cochrane Database of Systematic Reviews, 2012Co-Authors: Gashirai K Mbizvo, Jane L. Hutton, Pete Dixon, Anthony G MarsonAbstract:Background Epilepsy is an important neurological condition and drug resistance in epilepsy is particularly common in individuals with focal seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, Levetiracetam, when used as add-on treatment for controlling drug-resistant focal epilepsy. This is an update to a Cochrane Review that was originally published in 2001. Objectives To evaluate the effectiveness of Levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. Search methods We searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 7, 2012), and MEDLINE (1946 to August week 1, 2012). We also contacted the manufacturers of Levetiracetam and researchers in the field to seek any ongoing or unpublished trials. Selection criteria Randomised, placebo-controlled trials of add-on Levetiracetam treatment in people with drug-resistant focal epilepsy. Data collection and analysis Two review authors independently selected trials for inclusion, assessed trials for bias, extracted data, and evaluated the overall quality of evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response); less than 50% reduction in focal seizure frequency (non-response); treatment withdrawal; adverse effects (including a specific analysis of changes in behaviour); cognitive effects and quality of life (QoL). Risk ratios (RR) with 95% confidence intervals (CIs) were used as measures of effect (99% CIs for adverse effects). Primary analyses were Intention-to-Treat (ITT). Dose response and inter-trial heterogeneity were evaluated in regression models. Main results Eleven trials (1861 participants) were included. They predominantly possessed low risks of bias. Participants were adults in nine trials (1565 participants) and children in the remaining two trials (296 participants). The dose of Levetiracetam tested was 1000 to 4000 mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24 weeks. For the 50% or greater reduction in focal seizure frequency outcome, the RR was significantly in favour of Levetiracetam at all doses. The naive estimates, ignoring dose, showed children (52% responded) as better responders than adults (39% responded) on Levetiracetam. 25% of children and 16% of adults responded to placebo. The Number Needed to Treat for an additional beneficial outcome for children and adults was four (95% CI three to seven) and five (95% CI four to six), respectively. The significant levels of statistical heterogeneity between trials on adults precluded valid provision of an overall RR (ignoring dose). Results for the two trials that tested Levetiracetam 2000 mg on adults were sufficiently similar to be combined to give an RR for 50% or greater reduction in focal seizure frequency of 4.91 (95% CI 2.75 to 8.77), with an RR of 0.68 (95% CI 0.60 to 0.77) for non-response. At this dose, 37% and 8% of adults were responders in the Levetiracetam and placebo groups, respectively. Regression analysis demonstrated that much of the heterogeneity between adult trials was likely to be explained by different doses of Levetiracetam tested and different years of trial publication. There was no evidence of statistical heterogeneity between trials on children. For these trials, the RR for 50% or greater reduction in focal seizure frequency was 1.91 (95% CI 1.38 to 2.63), with an RR of 0.68 (95% CI 0.56 to 0.81) for non-response. 27% of children responded. Participants were not significantly more likely to have Levetiracetam withdrawn (RR 0.98; 95% CI 0.73 to 1.32 and RR 0.80; 95% CI 0.43 to 1.46 for adults and children, respectively). For adults, somnolence (RR 1.51; 99% CI 1.06 to 2.17) and infection (RR 1.76; 99% CI 1.03 to 3.02) were significantly associated with Levetiracetam. Accidental injury was significantly associated with placebo (RR 0.60; 99% CI 0.39 to 0.92). No individual adverse effect was significantly associated with Levetiracetam in children. Changes in behaviour were negligible in adults (1% affected; RR 1.79; 99% CI 0.59 to 5.41) but significant in children (23% affected; RR 1.90; 99% CI 1.16 to 3.11). Cognitive effect and QoL outcomes suggested that Levetiracetam had a positive effect on cognition and some aspects of QoL in adults. In children, Levetiracetam did not appear to alter cognitive function but there was evidence of worsening in certain aspects of child behaviour. The overall quality of evidence used was high. Authors' conclusions This update adds seven more trials to the original review, which contained four trials. At every dose analysed, Levetiracetam significantly reduced focal seizure frequency relative to placebo. This indicates that Levetiracetam can significantly reduce focal seizure frequency when it is used as an add-on treatment for both adults and children with drug-resistant focal epilepsy. As there was evidence of significant levels of statistical heterogeneity within this positive effect it is difficult to be precise about the relative magnitude of the effect. At a dose of 2000 mg, Levetiracetam may be expected to be 3.9 times more effective than placebo; with 30% of adults being responders at this dose. At a dose of 60 mg/kg/day, Levetiracetam may be expected to be 0.9 times more effective than placebo; with 25% of children being responders at this dose. When dose was ignored, children were better responders than adults by around 4% to 13%. The results grossly suggest that one child or adult may respond to Levetiracetam for every four or five children or adults, respectively, that have received Levetiracetam rather than placebo. The drug seems to be well tolerated in both adults and children although non-specific changes in behaviour may be experienced in as high as 20% of children. This aspect of the adverse-effect profile of Levetiracetam was analysed crudely and requires further investigation and validation. It seems reasonable to continue the use of Levetiracetam in both adults and children with drug-resistant focal epilepsy. The results cannot be used to confirm longer-term or monotherapy effects of Levetiracetam or its effects on generalised seizures. The conclusions are largely unchanged from those in the original review. The most significant contribution of this update is the addition of paediatric data into the analysis.
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Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review.
Epilepsy research, 2001Co-Authors: Anthony G Marson, John Paul Leach, Jane L. Hutton, S Castillo, S White, R Chaisewikul, Michael Privitera, David ChadwickAbstract:Abstract Objective: To undertake a systematic review and meta-analysis of placebo controlled add-on trials of Levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy. Methods: We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for Levetiracetam and remacemide. Results: We found four trials (1023 patients) of Levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62–5.44), 2.51 (1.88–3.33), 1.59 (0.91–2.97) and 2.46 (1.61–3.79), respectively. There was evidence for increasing effect with increasing dose for Levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88–1.66), 1.72 (1.35–2.18), 1.90 (1.00–3.60) and 1.64 (1.02–2.62), respectively. Conclusions: These data suggest a useful effect for Levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable ‘responder-withdrawal ratio’ followed by zonisamide and oxcarbazepine.
Edouard Hirsch - One of the best experts on this subject based on the ideXlab platform.
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Levetiracetam as add on therapy for idiopathic generalized epilepsy syndromes with onset during adolescence analysis of two randomized double blind placebo controlled studies
Epilepsy Research, 2009Co-Authors: William Rosenfeld, Selim R Benbadis, Pascal Edrich, Carlo Alberto Tassinari, Edouard HirschAbstract:Summary Purpose To assess the efficacy and tolerability of adjunctive Levetiracetam in idiopathic generalized epilepsy (IGE) syndromes with onset during adolescence: juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and generalized tonic–clonic seizures on awakening (GTCSA). Methods Supplementary analysis of two double-blind, placebo-controlled trials. Patients received Levetiracetam (target dose: adults 3000mg/day; children 60mg/kg/day; n =15 JAE, 78 JME, and 22 GTCSA) or placebo ( n =12 JAE, 89 JME, and 27 GTCSA) for 16–24 weeks (including 4-week uptitration) in addition to 1–2 antiepileptic drugs. Results Responder rates (≥50%) were significantly higher for Levetiracetam versus placebo for JAE (53.3% vs. 25.0%; p =0.004), JME (61.0% vs. 24.7%; p p =0.024). Seizure freedom rates were significantly higher for Levetiracetam versus placebo for JME (20.8% vs. 3.4%; p =0.002); differences between treatment groups for JAE (33.3% vs. 8.3%; p =0.15) and GTCSA (23.8% vs. 11.1%; p =0.45) appeared to be clinically relevant, but did not reach statistical significance. The most frequent adverse events on Levetiracetam were headache (Levetiracetam 16.8% and placebo 14.8%) and somnolence (Levetiracetam 9.7% and placebo 3.9%). Conclusions Adjunctive Levetiracetam was well tolerated and provided effective seizure control over 16–24 weeks in patients with insufficiently controlled IGE syndromes with onset during adolescence (JAE, JME, and GTCSA), supporting Levetiracetam's broad spectrum of efficacy.
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effects of Levetiracetam a novel antiepileptic drug on convulsant activity in two genetic rat models of epilepsy
Epilepsy Research, 1995Co-Authors: A T Gower, M Noyer, Edouard Hirsch, Any Boehrer, C MarescauxAbstract:The anticonvulsant effects of Levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, Levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, Levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of Levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with Levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.
Cenk Tek - One of the best experts on this subject based on the ideXlab platform.
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effects of Levetiracetam on tardive dyskinesia a randomized double blind placebo controlled study
The Journal of Clinical Psychiatry, 2008Co-Authors: Scott W Woods, John R Saksa, Bruce C Baker, Shuki J Cohen, Cenk TekAbstract:Objective The goal of this study was to evaluate the efficacy and safety of Levetiracetam versus placebo for tardive dyskinesia (TD). Method This double-blind, placebo-controlled, randomized study was conducted at the Connecticut Mental Health Center between September 2004 and April 2006. Antipsychotic-treated patients meeting Glazer-Morgenstern criteria for TD were assigned at random to receive Levetiracetam 500 mg/day to 3000 mg/day or placebo for 12 weeks. After completion of 12 weeks, patients were permitted to receive open-label Levetiracetam for a further 12 weeks. The principal efficacy outcome measure was improvement in the Abnormal Involuntary Movement Scale (AIMS) total score. Safety was assessed with an adverse event scale, psychiatric symptom rating scales, weight, and hematologic tests. Results A total of 50 patients were randomly assigned to treatment. AIMS total scores were moderate in severity at baseline. Mixed regression models revealed that AIMS total scores declined 43.5% from baseline in the Levetiracetam group compared to 18.7% for placebo (p = .022). Patients continuing Levetiracetam in the open-label phase continued to improve, and patients crossed over to open-label Levetiracetam improved to a similar degree as those initially assigned. Levetiracetam was well tolerated. Conclusion Levetiracetam appeared effective for TD in this study. The mechanisms of its therapeutic effect are unclear but may involve reducing neuronal hypersynchrony in basal ganglia. Future studies should attempt to replicate the current results. Trial registration clinicaltrials.gov Identifier: NCT00291213.
Scott D. Nei - One of the best experts on this subject based on the ideXlab platform.
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Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction.
Neurocritical care, 2016Co-Authors: Andrea M. New, Scott D. Nei, Kianoush Kashani, Alejandro A. Rabinstein, Erin FrazeeAbstract:Background Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate Levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe Levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction.
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Levetiracetam pharmacokinetics during continuous venovenous hemofiltration and acute liver dysfunction
Neurocritical Care, 2016Co-Authors: Andrea M. New, Scott D. Nei, Kianoush Kashani, Alejandro A. Rabinstein, Erin FrazeeAbstract:Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate Levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe Levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction. This is a case report of a single patient. A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of Levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12–46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h. Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric Levetiracetam regimen.
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Levetiracetam pharmacokinetics in a patient receiving continuous venovenous hemofiltration and venoarterial extracorporeal membrane oxygenation
Pharmacotherapy, 2015Co-Authors: Scott D. Nei, Kianoush Kashani, Erica D Wittwer, Erin FrazeeAbstract:Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of Levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that Levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous Levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new-onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5-39.8 μg/ml) and trough (ranging from 13.9-18.2 μg/ml) concentrations. Elimination half-life ranged from 8.7-10.1 hours. Renal dysfunction reduces Levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial Levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.
