- Development and clinical applications of the dried blood spot method for therapeutic drug monitoring of anti-epileptic drugs. [Journal Article]
- BCBasic Clin Pharmacol Toxicol 2019 Jun 14
- Anti-epileptic drugs (AEDs) have various pharmacokinetic profiles, inter-individual variabilities, high possibilities of drug-drug interactions and narrow therapeutic indices. To provide optimal trea…
Anti-epileptic drugs (AEDs) have various pharmacokinetic profiles, inter-individual variabilities, high possibilities of drug-drug interactions and narrow therapeutic indices. To provide optimal treatment for patients, therapeutic drug monitoring (TDM) is necessary. However, TDM requires sufficient quantities of blood samples to measure drug concentrations. Therefore, TDM could be a burden, particularly in paediatric cases. A good alternative that overcomes these disadvantages is the dried blood spot (DBS) method, which is simple, convenient to use and less invasive, requiring a lower quantity of blood than traditional blood sampling methods. However, the DBS method is affected by haematocrit (Hct) levels to varying extents depending on the drug properties. In addition, different papers with varying characteristics are available for use when applying the DBS method. Therefore, it has not yet been applied to TDM in clinical practice. To achieve this, several steps are required, including method development, method validation and clinical validation. Currently, the development status of the DBS method is different for each AED and unclear. Therefore, we assessed the development status of the following 19 AEDs in 26 studies: lamotrigine, valproic acid, levetiracetam, phenytoin, topiramate, carbamazepine, carbamazepine-epoxide, gabapentin, phenobarbital, pregabalin, clobazam, clonazepam, ethosuximide, felbamate, monohydroxycarbamazepine, nitrazepam, rufinamide, vigabatrin and zonisamide. Among them, carbamazepine, lamotrigine, topiramate and valproic acid have been developed such that they are nearly available for TDM. In addition, Whatman 903 Protein Saver Cards and concentration analysis by liquid chromatograph with triple quadrupole mass spectrometer were used most often. This article is protected by copyright. All rights reserved.
- Novel seizure outcomes in patients with Lennox-Gastaut syndrome: Post hoc analysis of seizure-free days in rufinamide Study 303. [Journal Article]
- EOEpilepsia Open 2019; 4(2):275-280
- Drug development for patients with Lennox-Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient…
Drug development for patients with Lennox-Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure efficacy parameters related to QoL in pediatric patients with LGS, using seizure diary data from rufinamide Study 303 (NCT01405053).
- GeneReviews®: SCN1A Seizure Disorders [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- SCN1A seizure disorders encompass a spectrum that ranges from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable ch…
SCN1A seizure disorders encompass a spectrum that ranges from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Phenotypes with intractable seizures including Dravet syndrome are often associated with cognitive decline. Less commonly observed phenotypes include myoclonic astatic epilepsy (MAE), Lennox-Gastaut syndrome, infantile spasms, epilepsy with focal seizures, and vaccine-related encephalopathy and seizures. The phenotype of SCN1A seizure disorders can vary even within the same family.
- Making Rash Decisions in Epilepsy: Evaluating Hypersensitivity Reactions to Anti-seizure Medications. [Journal Article]
- ECEpilepsy Curr 2019 Mar-Apr; 19(2):96-98
- CONCLUSIONS: Although allergic reactions to AEDs are rare, they are of significance because they can cause life-threatening severe cutaneous drug reactions. Therefore, patients receiving AEDs, especially aromatic AEDs, must be monitored closely. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Antiepileptic Drugs: An Analysis of the US Food and Drug Administration Adverse Event Reporting System Borrelli EP, Lee EY, Descoteaux AM, Kogut SJ, Caffrey AR. Epilepsia. 2018;59(12):2318-2324.Although AEDs as a class were associated with 9 times the risk of SJS/TEN compared with non-AEDs, there were 6 AEDs with risk estimates greater than 20. Increased awareness of this risk among both prescribers and patients, particularly variations in risk among different AEDs, along with education on early recognition of SJS/TEN signs/symptoms, may help mitigate the number and severity of these adverse events.
- Intractable Generalized Epilepsy: Therapeutic Approaches. [Review]
- CNCurr Neurol Neurosci Rep 2019 Feb 26; 19(4):16
- To summarize recent developments in therapeutic options, both medical and surgical, for patients with drug-resistant generalized epilepsy syndromes, which continue to be a multifaceted challenge for …
To summarize recent developments in therapeutic options, both medical and surgical, for patients with drug-resistant generalized epilepsy syndromes, which continue to be a multifaceted challenge for patients and physicians.
- Rufinamide for seizures. [Review]
- APAust Prescr 2019; 42(1):38-39
- Use of Newer Anticonvulsants for the Treatment of Status Epilepticus. [Review]
- PPharmacotherapy 2019; 39(3):297-316
- Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic…
Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super-refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25-100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17-60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting.
- Newer Antiepileptic Drugs Discontinuation due to Adverse Effects: An Observational Study. [Journal Article]
- AIAnn Indian Acad Neurol 2019 Jan-Mar; 22(1):27-30
- CONCLUSIONS: AEs in newer antiepileptic drugs are extremely prevalent. Our observation revealed that skin rashes and paresthesia were the most probable causes of treatment discontinuation because of AEs.
- LC-MS/MS-Based Quantification of 9 Antiepileptic Drugs From a Dried Sample Spot Device. [Journal Article]
- TDTher Drug Monit 2019; 41(3):331-339
- CONCLUSIONS: The application of the LC-MS/MS method allowed the authors to obtain a very specific, sensitive, and rapid (total runtime = 10.3 minutes) quantification of 9 AEDs starting from very low volumes of plasma samples. The main advantage of DPS over wet samples is room temperature storage and shipment, which lowers shipment costs and makes it suitable for routine TDM. Moreover, in comparison with other alternative matrices, DPS allows for the use of the same therapeutic ranges on which routine TDM is based. DPS on DSSD can thus be considered as a useful and cheap tool for the broader application of TDM.
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- Cannabidiol (Epidiolex) for epilepsy. [Journal Article]
- MLMed Lett Drugs Ther 2018 Nov 05; 60(1559):182-184