Severe cutaneous adverse reaction associated with antiseizure medications: Diagnosis, management, and prevention

Brandt, Christian; McGuire, Lockhart B.; Uetrecht, Jack

doi:10.1016/j.yebeh.2021.107844

Cited by 5 publications

(9 citation statements)

References 105 publications

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“…The results from FAERS showed a statistical association between topiramate and DRESS. However, after using RGPS, a logistic regression analysis, the statistical association between topiramate and DRESS was no longer significant, whereas concomitant carbamazepine, lamotrigine, phenytoin, and zonisamide were shown to have statistical significance, consistent with previous findings [1,19]. This data suggests that topiramate may be an innocent bystander.…”

Section: Discussionsupporting

confidence: 88%

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A Comprehensive Analysis of Topiramate and Drug Reaction With Eosinophilia and Systemic Symptoms

Thoms

Muller

Schaufelberger

et al. 2023

Cureus

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IntroductionRecent publications have described drug reaction with eosinophilia and systemic symptoms (DRESS) with topiramate. Topiramate has been associated with other severe cutaneous adverse reactions, including Stevens-Johnson syndrome, but a relationship to DRESS has not been established. To determine if there is a causal association between topiramate and DRESS, we conducted a comprehensive review of the data in the Janssen Research & Development Global Safety Database (GSD), signaling databases, and the literature. MethodsThe primary data were post-marketing reports of DRESS in the Janssen topiramate GSD (cumulative through 1 July 2022), representing >14,000,000 patient-years (PY) exposure. Cases were reviewed, assigned a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score, and assessed for overall contribution of topiramate to DRESS based on temporality, concomitant medications, dechallenge/rechallenge, and baseline patient factors. Statistical disproportionality was evaluated in European Medicines Agency's EudraVigilance (EV) safety database and the United States Food and Drug Administration Adverse Event Reporting System (FAERS). For EV, the overall disproportionality threshold was the lower limit of the 95% confidence interval (CI) for the reporting odds ratio (ROR025) >1 and N ≥5. The overall threshold for FAERS was the Empirical Bayesian Geometric Mean (EBGM) ≥2, lower bound of the 90% CI (EB05) of >1, and N ≥3. To account for the role of concomitant drugs, Empirical Bayes regression-adjusted arithmetic mean (ERAM) scores were calculated, with a threshold ≥2, a lower bound of the 90% CI (ER05) of >1, and N ≥3. An integrated search of major biomedical literature was performed for reports of topiramate and DRESS. ResultsThere were 17 reports of DRESS in the GSD (reporting rate 0.12/100,000 PY). RegiSCAR scores ranged from -3 to 7 (average -0.4). No cases met full diagnostic criteria and were highly confounded by the presence of other suspect drugs. Disproportionality scores exceeded thresholds for statistical significance in FAERS (N=72, EBGM=2.06, EB05=1.69), but not in EV (N=33, ROR025=0.79). When accounting for co-administered drugs, ERAM was statistically significant for carbamazepine (4.53), lamotrigine (ERAM=6.54), phenytoin (ERAM=2.91), and zonisamide (ERAM=2.25) exceeding disproportionality thresholds, but the score of topiramate was no longer significant (0.25). ConclusionA comprehensive review of all available evidence does not support a causal association between topiramate and DRESS.

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Section: Discussionsupporting

confidence: 88%

“…Severe cutaneous adverse reactions (SCAR) have been widely reported with anti-seizure medications, including topiramate [1]. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are known to be associated with topiramate, as reflected in the product information [2].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Analysis of Topiramate and Drug Reaction With Eosinophilia and Systemic Symptoms

Thoms

Muller

Schaufelberger

et al. 2023

Cureus

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“…O período geral de incubação desde a exposição ao medicamento até os sintomas é de cerca de 4 a 28 dias e raramente é superior a 8 semanas (ZHANG et al, 2021). Aproximadamente 95% dos pacientes com SSJ/NET apresentam lesões hemorrágicas das membranas mucosas envolvendo os olhos, lábios, mucosa oral e genitália e, também, existe a possibilidade de ocorrer erosões na traquéia, brônquios, uretra e ânus (BRANDT, et al, 2021). O trato gastrointestinal pode estar envolvido, podendo ocorrer sangramento e perfuração do cólon.…”

Section: Diagnósticounclassified

Síndrome De Stevens-Johnson - Revisão De Literatura

LEVADA¹,

COSTA²,

MARIANO³

et al. 2023

Teoria E Prática Trauma E Emerge^ncia - Edição VII

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“…ASMs are associated with rare, but potentially life-threatening idiosyncratic adverse effects, including immune-mediated hypersensitivity reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-related rash with eosinophilia and systemic symptoms (DRESS). High starting doses and rapid rates of titration are contributing factors to the risk of severe cutaneous adverse reaction with several ASMs, including carbamazepine, lamotrigine, and phenytoin [19,20]. Starting treatment at a low dose with gradual dose increases may decrease the risk of these adverse reactions via desensitization [19,21].…”

Section: ''Start Low Go Slow" Titration To Reduce the Risk Of Immunemediated Idiosyncratic Adverse Effectsmentioning

confidence: 99%

“…High starting doses and rapid rates of titration are contributing factors to the risk of severe cutaneous adverse reaction with several ASMs, including carbamazepine, lamotrigine, and phenytoin [19,20]. Starting treatment at a low dose with gradual dose increases may decrease the risk of these adverse reactions via desensitization [19,21].…”

Section: ''Start Low Go Slow" Titration To Reduce the Risk Of Immunemediated Idiosyncratic Adverse Effectsmentioning

confidence: 99%

The importance of drug titration in the management of patients with epilepsy

Seiden

Connor²

2022

Epilepsy & Behavior

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The variable response to antiseizure medication (ASM) treatment and the numerous drug-and patientrelated factors that must be considered when initiating therapy make drug titration to an optimal and tolerable dose an essential component in the pharmacologic treatment of patients with epilepsy. When initiating a new ASM, a ''start low, go slow" titration approach is generally recommended and has been shown to reduce the risk of severe idiosyncratic reactions with certain medications and improve tolerability with regard to many frequently occurring central nervous system-related adverse effects (e.g., somnolence, dizziness). Many patients with epilepsy will require medication changes due to lack of efficacy or intolerability of the initial regimen. When this occurs, patients may be switched from one monotherapy to another or receive adjunctive therapy. When transitioning a patient from one ASM to another (referred to as monotherapy conversion or transitional polytherapy), there are several strategies for tapering the baseline ASM depending on the clinical scenario. Regardless of the particular strategy, the goal should be to discontinue the baseline ASM in order to prevent increased toxicity due to drug load. When adding on ASM therapy, flexible titration of the new ASM and adjustment of concomitant ASMs to achieve disease control with the lowest possible drug load (lowest numbers and lowest doses) may help improve tolerability of the add-on therapy. Communication with patients during the initiation of a new therapy may help patients adhere to the titration schedule, allowing them to reach their optimal maintenance dose.

show abstract

Severe cutaneous adverse reaction associated with antiseizure medications: Diagnosis, management, and prevention

Cited by 5 publications

References 105 publications

A Comprehensive Analysis of Topiramate and Drug Reaction With Eosinophilia and Systemic Symptoms

A Comprehensive Analysis of Topiramate and Drug Reaction With Eosinophilia and Systemic Symptoms

Síndrome De Stevens-Johnson - Revisão De Literatura

The importance of drug titration in the management of patients with epilepsy

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