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The Canadian Journal of Hospital... 2022Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line... (Review)
Review
BACKGROUND
Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy.
OBJECTIVE
To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults.
DATA SOURCES
MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020.
STUDY SELECTION AND DATA EXTRACTION
Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics.
DATA SYNTHESIS
Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam.
CONCLUSIONS
Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.
PubMed: 34987263
DOI: 10.4212/cjhp.v75i1.3254 -
Epilepsia Feb 2022Thyroid hormones play an essential role in central nervous system development, normal physiological brain function, and repair mechanisms. On one hand, thyroid hormone... (Review)
Review
Thyroid hormones play an essential role in central nervous system development, normal physiological brain function, and repair mechanisms. On one hand, thyroid hormone alterations influence cortical excitability, and on the other hand antiseizure medications (ASMs) are associated with alterations in thyroid hormone metabolism. Although this interaction has long been described, and epilepsy is a common and chronic neurological disease, studies describing the interplay are often small and retrospective. We performed a systematic review of the current literature on epilepsy, ASMs, and thyroid hormone metabolism according to PRISMA guidelines. Forty-seven studies were included. Most studies were retrospective cross-sectional studies (n = 25) and investigated thyroid function alterations in patients on older ASMs such as phenobarbital, phenytoin, carbamazepine, and valproate. Overall, almost one third of patients with epilepsy had thyroid hormone alterations, especially patients on valproate (25%) and carbamazepine (10%-25%). Studies with patients receiving polytherapy are scarce, but reported a higher risk for hypothyroidism in patients with older age (p = .004), female sex (p = .014), longer duration of epilepsy (p = .001), intractable epilepsy (p = .009), and polytherapy. Studies on newer ASMs are also limited, and further studies on an interplay with thyroid hormone homeostasis are essential to improve the care for epilepsy patients. ASMs are associated with alterations in thyroid hormone metabolism. Thyroid function monitoring is indicated in patients on ASMs, especially those with refractory epilepsy and those on polytherapy. We provide a practical guidance for thyroid function monitoring for the clinician taking care of patients on ASMs.
Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Homeostasis; Humans; Retrospective Studies; Thyroid Hormones; Valproic Acid
PubMed: 34750814
DOI: 10.1111/epi.17117 -
Neuro-oncology Practice Oct 2021Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic... (Review)
Review
BACKGROUND
Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.
METHODS
Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.
RESULTS
A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.
CONCLUSION
Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
PubMed: 34589231
DOI: 10.1093/nop/npab030 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures.... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
SEARCH METHODS
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
MAIN RESULTS
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.
AUTHORS' CONCLUSIONS
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
Topics: Anticonvulsants; Epilepsy; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazines
PubMed: 34554571
DOI: 10.1002/14651858.CD010062.pub3 -
Journal of the Neurological Sciences Oct 2021Seizure activity following spontaneous intracerebral hemorrhage (sICH) can worsen patients' comorbidity. However, data regarding whether seizure prophylaxis for sICH is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Seizure activity following spontaneous intracerebral hemorrhage (sICH) can worsen patients' comorbidity. However, data regarding whether seizure prophylaxis for sICH is associated with patients' poor functional outcome is inconclusive. We performed a systematic review and meta-analysis to assess the relationship between phenytoin prophylaxis and poor functional outcome after sICH.
METHODS
We conducted our search on PubMed, Scopus, and EMBASE databases as of October 30, 2020 for studies that included information on seizure prophylaxis and functional outcome in patients with sICH. Primary outcome was poor functional outcome at the longest follow-up in patients receiving seizure prophylaxis. The secondary outcome was poor functional outcome at 90 days follow-up. We conducted random effects meta-analysis and moderator analyses to detect sources of heterogeneity for our outcomes.
RESULTS
We included eleven studies in the final analysis with a total of 4268 patients. A moderator analysis further showed prospective studies had lower heterogeneity. We did not find an association between seizure prophylaxis and poor functional outcome at time of longest follow-up (OR 1.2, 95%CI 0.9-1.6, p-value = 0.22, I = 61%), nor at 90-day follow-up (OR 1.4, 95%CI 0.8-2.4, p-value = 0.24, I = 78%).
CONCLUSION
Seizure prophylaxis following sICH was not associated with worse functional outcomes at longest follow-up or at 90 days. Neither levetiracetam nor phenytoin was associated with outcome in our exploratory meta-regression, though there is a trend towards better outcomes in populations where there was a higher percentage of patients who received levetiracetam. More randomized trials are needed to confirm this observation.
Topics: Anticonvulsants; Cerebral Hemorrhage; Humans; Phenytoin; Piracetam; Prospective Studies; Seizures
PubMed: 34488044
DOI: 10.1016/j.jns.2021.117624 -
The Pharmacogenomics Journal Dec 2021Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform...
Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.
Topics: Analgesics; Anesthetics; Clinical Decision-Making; Decision Support Techniques; Evidence-Based Medicine; Humans; Perioperative Care; Pharmacogenetics; Pharmacogenomic Testing; Pharmacogenomic Variants; Predictive Value of Tests; Risk Assessment; Risk Factors
PubMed: 34376788
DOI: 10.1038/s41397-021-00248-2 -
Seizure Oct 2021Serotonin syndrome (SS) is a drug‑induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs... (Review)
Review
Serotonin syndrome (SS) is a drug‑induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs (AEDs) are known to have serotonergic properties and it can be hypothesized that such AEDs can cause SS. This study aims to review the literature on SS in patients receiving AEDs. We performed a systematic review of Scopus and MEDLINE/PUBMED for case reports and case series of SS where patients had received at least one AED at the onset of symptoms. The cases published in the English literature between 1 January 1991 and 1 April 2021 were included. Initial search identified 1263 articles of which 63 (76 patients) were included in the final analysis. Most of the included cases (53 cases, 70%) have been published in the last 10 years. The mean age of the 76 patients was 40.6 ± 17.8 years, and 51% of cases were females. These patients had been exposed to a total of 8 different types of AEDs. Valproic acid was the most common drug (29, 38%), followed by lamotrigine (22, 29%), gabapentin (16, 21%), pregabalin (seven, 9%), topiramate (five, 7%) and carbamazepine (two, 3%). There has been one case each with phenytoin and oxcarbazepine. Seven (9%) patients received more than one AEDs. Most patients (67, 88%) also received other serotoninergic agents. Only nine (12%) patients were on AEDs alone. The most common clinical condition for using AEDs was psychiatric disorders (36 patients, 47.3%), followed by migraine (17, 22.4%), other painful conditions (15, 19.7%), epilepsy (7, 9.2%), and perioperative conditions (8, 10.5%). Death was reported in two patients. We suggest that AEDs, because of their serotonergic properties, may induce SS, especially in patients who are on another serotonergic agent.
Topics: Adult; Anticonvulsants; Carbamazepine; Female; Humans; Middle Aged; Oxcarbazepine; Serotonin Syndrome; Topiramate; Young Adult
PubMed: 34153897
DOI: 10.1016/j.seizure.2021.06.004 -
The Cochrane Database of Systematic... Jun 2021Febrile seizures occurring in a child older than one month during an episode of fever affect 2-4% of children in Great Britain and the United States and recur in 30%.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Febrile seizures occurring in a child older than one month during an episode of fever affect 2-4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. This is an updated version of a Cochrane Review previously published in 2017.
OBJECTIVES
To evaluate primarily the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures; and also to evaluate any other drug intervention where there is a sound biological rationale for its use.
SEARCH METHODS
For the latest update we searched the following databases on 3 February 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 31 January 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We imposed no language restrictions and contacted researchers to identify continuing or unpublished studies.
SELECTION CRITERIA
Trials using randomised or quasi-randomised participant allocation that compared the use of antiepileptics, antipyretics or recognised Central Nervous System active agents with each other, placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
For the original review, two review authors independently applied predefined criteria to select trials for inclusion and extracted the predefined relevant data, recording methods for randomisation, blinding, and exclusions. For the 2016 update, a third review author checked all original inclusions, data analyses, and updated the search. For the 2020 update, one review author updated the search and performed the data analysis following a peer-review process with the original review authors. We assessed seizure recurrence at 6, 12, 18, 24, 36, 48 months, and where data were available at age 5 to 6 years along with recorded adverse effects. We evaluated the presence of publication bias using funnel plots.
MAIN RESULTS
We included 42 articles describing 32 randomised trials, with 4431 randomised participants used in the analysis of this review. We analysed 15 interventions of continuous or intermittent prophylaxis and their control treatments. Methodological quality was moderate to poor in most studies. We found no significant benefit for intermittent phenobarbital, phenytoin, valproate, pyridoxine, ibuprofen, or zinc sulfate versus placebo or no treatment; nor for diclofenac versus placebo followed by ibuprofen, paracetamol, or placebo; nor for continuous phenobarbital versus diazepam, intermittent rectal diazepam versus intermittent valproate, or oral diazepam versus clobazam. There was a significant reduction of recurrent febrile seizures with intermittent diazepam versus placebo or no treatment at six months (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.48 to 0.85; 6 studies, 1151 participants; moderate-certainty evidence), 12 months (RR 0.69, 95% CI 0.56 to 0.84; 8 studies, 1416 participants; moderate-certainty evidence), 18 months (RR 0.37, 95% CI 0.23 to 0.60; 1 study, 289 participants; low-certainty evidence), 24 months (RR 0.73, 95% CI 0.56 to 0.95; 4 studies, 739 participants; high-certainty evidence), 36 months (RR 0.58, 95% CI 0.40 to 0.85; 1 study, 139 participants; low-certainty evidence), 48 months (RR 0.36, 95% CI 0.15 to 0.89; 1 study, 110 participants; moderate-certainty evidence), with no benefit at 60 to 72 months (RR 0.08, 95% CI 0.00 to 1.31; 1 study, 60 participants; very low-certainty evidence). Phenobarbital versus placebo or no treatment reduced seizures at six months (RR 0.59, 95% CI 0.42 to 0.83; 6 studies, 833 participants; moderate-certainty evidence), 12 months (RR 0.54, 95% CI 0.42 to 0.70; 7 studies, 807 participants; low-certainty evidence), and 24 months (RR 0.69, 95% CI 0.53 to 0.89; 3 studies, 533 participants; moderate-certainty evidence), but not at 18 months (RR 0.77, 95% CI 0.56 to 1.05; 2 studies, 264 participants) or 60 to 72 months follow-up (RR 1.50, 95% CI 0.61 to 3.69; 1 study, 60 participants; very low-certainty evidence). Intermittent clobazam compared to placebo at six months resulted in a RR of 0.36 (95% CI 0.20 to 0.64; 1 study, 60 participants; low-certainty evidence), an effect found against an extremely high (83.3%) recurrence rate in the controls, a result that needs replication. When compared to intermittent diazepam, intermittent oral melatonin did not significantly reduce seizures at six months (RR 0.45, 95% CI 0.18 to 1.15; 1 study, 60 participants; very-low certainty evidence). When compared to placebo, intermittent oral levetiracetam significantly reduced recurrent seizures at 12 months (RR 0.27, 95% CI 0.15 to 0.52; 1 study, 115 participants; very low-certainty evidence). The recording of adverse effects was variable. Two studies reported lower comprehension scores in phenobarbital-treated children. Adverse effects were recorded in up to 30% of children in the phenobarbital-treated groups and 36% in benzodiazepine-treated groups. We found evidence of publication bias in the meta-analyses of comparisons for phenobarbital versus placebo (seven studies) at 12 months but not at six months (six studies); and valproate versus placebo (four studies) at 12 months. There were too few studies to identify publication bias for the other comparisons. The methodological quality of most of the included studies was low or very low. Methods of randomisation and allocation concealment often did not meet current standards, and 'treatment versus no treatment' was more commonly seen than 'treatment versus placebo', leading to obvious risks of bias. AUTHORS' CONCLUSIONS: We found reduced recurrence rates for intermittent diazepam and continuous phenobarbital, with adverse effects in up to 30% of children. The apparent benefit for clobazam treatment in one trial needs to be replicated. Levetiracetam also shows benefit with a good safety profile; however, further study is required. Given the benign nature of recurrent febrile seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of medical services and information on recurrence, first aid management, and, most importantly, the benign nature of the phenomenon.
Topics: Anticonvulsants; Antipyretics; Child; Child, Preschool; Confidence Intervals; Humans; Infant; Placebos; Publication Bias; Randomized Controlled Trials as Topic; Recurrence; Seizures, Febrile
PubMed: 34131913
DOI: 10.1002/14651858.CD003031.pub4 -
Journal of Tropical Pediatrics May 2021To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Levetiracetam vs. Phenytoin as Second Line Antiseizure Medication for Pediatric Convulsive Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).
DATA SOURCE
PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.
STUDY SELECTION
Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020.
DATA EXTRACTION
The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO.
DATA SYNTHESIS
Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias.
CONCLUSION
The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.
Topics: Anticonvulsants; Child; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus
PubMed: 34089322
DOI: 10.1093/tropej/fmab014 -
Pharmacogenomics Jul 2021Phenytoin is metabolized through CYP2C9 and CYP2C19 Polymorphisms of and may increase plasma concentration and side effects. Systematic review and meta-analysis were... (Meta-Analysis)
Meta-Analysis
Phenytoin is metabolized through CYP2C9 and CYP2C19 Polymorphisms of and may increase plasma concentration and side effects. Systematic review and meta-analysis were performed to evaluate the effects of and polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Eight observational studies, comprising a total of 633 patients were included. Michaelis-Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p < 0.00001, p < 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, <0.0001). The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1-3.4 mg/kg/day.
Topics: Anticonvulsants; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Epilepsy; Humans; Observational Studies as Topic; Phenytoin; Polymorphism, Genetic
PubMed: 34060344
DOI: 10.2217/pgs-2020-0151