scholarly journals Clinical utility of therapeutic drug monitoring of antiepileptic drugs

2019 ◽  
Vol 10 (4) ◽  
pp. 344-355 ◽  
Author(s):  
Zanab Al-Roubaie ◽  
Elena Guadagno ◽  
Agnihotram V. Ramanakumar ◽  
Afsheen Q. Khan ◽  
Kenneth A. Myers
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Effects ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Seizure Control ◽  
Therapeutic Drug ◽  
Seizure Outcome ◽  
Randomized Controlled ◽  
Patient Reported ◽  
Positive Effect

ObjectiveTo systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy.MethodsWe searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925.ResultsSixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line.ConclusionsIf optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

Therapeutic Drug Monitoring of Antiepileptic Drugs in a Tertiary Care Hospital in India

2015 ◽  
Vol 38 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Natarajan Harivenkatesh ◽  
Natarajan Haribalaji ◽  
Darling Chellathai David ◽  
C. M. Prabu Kumar
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Therapeutic Drug ◽  
Care Hospital

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

scholarly journals Therapeutic Drug Monitoring of Second- and Third-Generation Antiepileptic Drugs: Insights From a College of American Pathologists Proficiency Testing Survey

2021 ◽  
Author(s):  
Matthew D. Krasowski ◽  
Thomas A. Long ◽  
Christine L. H. Snozek ◽  
Annabel Dizon ◽  
Barbarajean Magnani ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Proficiency Testing ◽  
Drug Monitoring ◽  
First Generation ◽  
Therapeutic Drug ◽  
Third Generation ◽  
Enzyme Immunoassays ◽  
Steady Growth ◽  
Survey Results

Context.— Therapeutic drug monitoring has traditionally been widely used for first-generation antiepileptic drugs (AEDs) such as carbamazepine and phenytoin. The last 2 decades have seen the introduction of second- and third-generation AEDs (eg, lamotrigine, levetiracetam, and topiramate) into clinical practice. Objective.— To use data from the College of American Pathologists Therapeutic Drug Monitoring, Extended proficiency testing survey to determine the performance of assays used for therapeutic drug monitoring of newer AEDs, including comparison of enzyme immunoassay and chromatographic techniques. Design.— Six years of proficiency testing surveys were reviewed (2013–2018). Results.— Steady growth was seen in participant volumes for newer AEDs. The analytical performance of automated enzyme immunoassays for lamotrigine, levetiracetam, and topiramate was similar to that of chromatographic methods, consistent with published literature using patient samples for comparisons. The majority of participating laboratories now use enzyme immunoassays to measure levetiracetam. Conclusions.— Survey results reflect steadily growing interest in therapeutic drug monitoring of newer AEDs. The increasing availability of robust immunoassays for new AEDs should facilitate their clinical utility, especially for clinical laboratories that do not perform chromatographic assays for therapeutic drug monitoring.

scholarly journals Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment

2019 ◽  
Vol 87 (1) ◽  
pp. 22-29 ◽  
Author(s):  
Irene Aícua‐Rapún ◽  
Pascal André ◽  
Andrea O. Rossetti ◽  
Philippe Ryvlin ◽  
Andreas F. Hottinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Randomized Trial ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
Dosage Adjustment ◽  
Therapeutic Drug

Pharmacokinetic Properties of New Antiepileptic Drugs

2005 ◽  
Vol 18 (6) ◽  
pp. 444-460 ◽  
Author(s):  
Michele Y. Splinter
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
The United States ◽  
Therapeutic Drug ◽  
Kinetic Properties ◽  
New Antiepileptic Drugs ◽  
Drug Concentrations ◽  
Pharmacokinetic Properties

Eight new antiepileptic drugs (AEDs) have been approved for use within the United States within the past decade. They are felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide. These afford clinicians with more options to increase efficacy and tolerability in the treatment of patients with epilepsy. Pharmacokinetic properties and drug interactions with other AEDs and other medications taken for comorbidities are individually discussed for each of these new agents. Drug concentrations are not routinely monitored for these newer agents, and there have been few studies designed to investigate their concentration-effect relationships. For most of these medications, the concentrations observed in responders and nonresponders overlap considerably and levels associated with efficacy are often associated with adverse events, complicating the definition of target ranges. Also, epilepsy manifests itself sporadically causing difficulty in clinically monitoring efficacy of medications. Therapeutic drug monitoring provides for the individualization of treatment for these agents, which is important because they demonstrate significant variability in inter- and intraindividual pharmaco-kinetic properties. Therapeutic drug monitoring also allows for identification of noncompliance, drug interactions, and toxicity. Current knowledge of the relationships between efficacy, toxicity, and drug concentrations is discussed.

Levetiracetam for Mood Stabilization and Maintenance of Seizure Control Following Multiple Treatment Failures

2005 ◽  
Vol 39 (11) ◽  
pp. 1928-1931 ◽  
Author(s):  
Steven C Stoner ◽  
Jessica W Lea ◽  
Angel L Wolf ◽  
Arnaldo A Berges
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Events ◽  
Drug Monitoring ◽  
Adverse Reactions ◽  
Seizure Control ◽  
Therapeutic Drug ◽  
Multiple Treatment ◽  
Case Summary ◽  
Mood Stabilization ◽  
Antiepileptic Medications

OBJECTIVE To report the case of a patient who experienced adverse events in succession to antiepileptic medications being used for both antiepileptic and mood-stabilization benefit. CASE SUMMARY A 46-year-old white woman developed hyponatremia with carbamazepine, hyperammonemia with divalproex, cognitive impairment with topiramate, and hyponatremia with oxcarbazepine. The patient was stabilized physically and psychiatrically on levetiracetam without any noted adverse events. DISCUSSION The adverse events in this report have been associated with the medications in question. The patient's presentation is unique, as she developed adverse events in succession to antiepileptic drugs being used to treat both a seizure disorder and symptoms of mood instability. The Naranjo rankings for the reported adverse events indicated the associations were probable (carbamazepine, divalproex, oxcarbazepine) and possible (topiramate). After repeated incidences of intolerability to these drugs, levetiracetam was initiated and provided both seizure control and mood-stabilizing benefits, which eventually led to hospital discharge. CONCLUSIONS Levetiracetam may provide mood-stabilizing qualities through a mechanism that is unique from that of other antiepileptic agents used for their mood-stabilizing properties. There are potential advantages with levetiracetam, as no specific therapeutic drug monitoring parameters need to be followed after its introduction. Additionally, this case emphasizes the importance of therapeutic drug monitoring and frequent assessments to prevent physical and psychiatric adverse reactions.

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