Stevens‐Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs: An analysis of the US Food and Drug Administration Adverse Event Reporting System

Borrelli, E.; Lee, Erica Y.; Descoteaux, Andrew; Kogut, Stephen; Caffrey, Aisling R.

doi:10.1111/epi.14591

Cited by 71 publications

(56 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serious skin reactions such as DRESS have been reported with AEDs such as phenytoin, carbamazepine, phenobarbital, and lamotrigine. [21][22][23][24] In a previous study of lamotrigine, withdrawal because of skin rash was reduced to placebo levels by lowering the starting dose and increasing the time between dose escalations; this approach has been recommended only while the patient is under careful surveillance. 21,25,26 The previously cited ongoing long-term safety study of cenobamate in focal epilepsy patients demonstrates that slow titration up from 12.5 mg/day to a maintenance dose of 100-400 mg/day with 2-week dose increments over 12 weeks resulted in no incidences of DRESS.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending‐Dose Studies in Healthy Subjects

Vernillet

Greene

Kamin

2020

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

Cenobamate (YKP3089) is an antiepileptic drug recently approved by the Food and Drug Administration for the treatment of focal (partial-onset) seizures in adults. The objectives of a first-in-human single-ascending-dose study and 3 multiple-ascending-dose studies were to characterize the pharmacokinetics, safety, and tolerability of cenobamate after single-dose and multiple-dose administration in healthy subjects. The 4 randomized, placebo-controlled, doubleblind studies were conducted in 210 healthy subjects receiving single (5 to 750 mg) or multiple (50 to 600 mg/day) oral doses of cenobamate or placebo using capsule formulation. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory evaluations. Maximum plasma concentrations of cenobamate were observed between 0.8 and 4.0 hours after oral administration. C max increased in a dose-proportional manner for single-and multiple-dose administration across all tested doses. Although the AUC of cenobamate increased in a more than dose-proportional manner after single-dose administration, a dose-proportional increase in cenobamate AUC τ was observed after multiple dosing from 50 to 500 mg/day. Cenobamate exhibited low oral clearance (decreasing from approximately 1.4 to 0.50 L/h with dose increase) and long terminal half-life (range, approximately 30 to 76 hours with increasing dose). Steady-state was attained after approximately 2 weeks, and the accumulation ratio was approximately 5 over the 50 to 300 mg/day range. The pharmacokinetic characteristics of cenobamate are consistent with once-daily dosing. Most TEAEs were mild in severity, 2 serious TEAEs were reported, and no deaths occurred across all studies. Except for multiple daily doses of 600 mg, all doses were generally well tolerated.Despite the development of more than a dozen new antiepileptic drugs (AEDs) over the past 20 years, significant progress in improving the efficacy and tolerability of therapies for patients with epilepsy has been limited by the efficacy and safety of these compounds. [1][2][3][4][5] Approximately 30% to 56% of patients with epilepsy continue to experience uncontrolled seizures during therapy with existing AEDs. 2,3,5,6 Continued seizures despite AED treatment have been associated with increased risk of mood disorders, limitations in education and work opportunities, and greater stigma for patients. 7 Many patients report reduced quality of life because of the failure of existing AEDs to control seizures or because of their intolerable side effects. 7,8 Thus, there remains a clear unmet need for new AEDs that are effective, safe, and tolerable. Cenobamate (YKP3089) is an AED recently approved by the US Food and Drug Administration (FDA) for the treatment of adults with focal (partialonset) seizures (Supplemental Figure). Although the mechanism by which cenobamate exerts its therapeutic effect has yet to be fully elucidated, it has been shown to involve enhancement of fast and slow inactivation of

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending‐Dose Studies in Healthy Subjects

Vernillet

Greene

Kamin

2020

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

show abstract

“…Hence, moderate and severe allergic reactions do occur. A recent meta-analysis concluded that of all AEDs, ZNS has the highest risk of potentially life-threatening allergic reactions like Steven-Johnson syndrome and toxic epidermal necrolysis [70].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Reimers

Ljung

2019

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.

show abstract

“…As a class, antiepileptics have a greater risk of hypersensitivity reactions, including SJS/TEN, than other drug classes, especially in children. 4,5 Breastfed infants should be watched carefully for rashes. Routine measurement of infant serum levels is generally not necessary except to rule out toxicity if there is a concern.…”

Section: Discussionmentioning

confidence: 99%

“…Although no adverse reactions have been reported in breastfed infants, zonisamide may have the highest risk of SJS/TEN of all antiepileptics. 4…”

Section: Zonisamidementioning

confidence: 99%

Antiepileptic Drugs During Breastfeeding

Anderson

2020

Breastfeeding Medicine

View full text Add to dashboard Cite

Changes to LactMed: The National Library of Medicine has recently made some decisions that affect LactMed. First, all Toxnet databases are being either dropped, combined with other databases, or transitioned to a different platform. LactMed will now be available only at the NLM Bookshelf site: https://www.ncbi.nlm.nih.gov/books/NBK501922/ Information in the database is the same as on the former Toxnet site and it will continue to be updated monthly, around the third Tuesday of each month. Second, the LactMed Ò app will be dropped. This means that LactMed will only be available via a browser on the NLM Bookshelf as noted above. The app that you might have on your device at the current time is about 2 years out of date, so you are encouraged to use NLM Bookshelf to access LactMed.

show abstract

Stevens‐Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs: An analysis of the US Food and Drug Administration Adverse Event Reporting System

Cited by 71 publications

References 36 publications

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending‐Dose Studies in Healthy Subjects

Pharmacokinetics of Cenobamate: Results From Single and Multiple Oral Ascending‐Dose Studies in Healthy Subjects

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Antiepileptic Drugs During Breastfeeding

Contact Info

Product

Resources

About