phenytoin / Generic mfg. - LARVOL DELTA

P043 A scoping review of patient metrics, aetiology, management and complications in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). (PubMed, Br J Dermatol) - "The most common causative individual drugs were lamotrigine (n = 76), carbamazepine (n = 71), phenytoin (n = 45), co-trimoxazole (n = 36) and pembrolizumab (n = 28). Regarding treatments, steroids are the mainstay, alongside intravenous immunoglobulin and ciclosporin. The range of complications emphasizes the need for a multidisciplinary management approach both in the short- and longer-term care of patients."

Journal • Conjunctivitis • Dermatology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease • Keratitis • Liver Failure • Novel Coronavirus Disease • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Steven-Johnson Syndrome

Prediction of anti-epileptic drug response of patients based on peripheral blood RNA profiles and machine learning. (PubMed, Int J Clin Pharmacol Ther) - "The model of a quadratic support vector machine with a pretreatment of principal component analysis is a potential tool for predicting the response of patients with epilepsy to drug treatment."

Journal • CNS Disorders • Epilepsy

Chronic Ocular Complications in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Clinical Features and Surgical Management in a Brazilian Tertiary Center. (PubMed, Cornea) - "Our findings highlight the significant burden of severe ocular surface disease, the predominance of dipyrone as a causative drug in this population, and the need for complex surgical interventions in a significant proportion of cases. These results underscore the importance of early management of ocular complications, long-term follow-up, and access to advanced therapeutic strategies."

Journal • Dry Eye Disease • Inflammation • Ophthalmology • Steven-Johnson Syndrome • Transplantation

Postoperative seizure prophylaxis after craniotomy: a current evidence and ongoing controversy. (PubMed, Ann Med Surg (Lond)) - "Levetiracetam has largely replaced phenytoin in modern practice due to improved tolerability, though neither has shown clear superiority in preventing late seizures. Most data support selective, rather than routine, prophylaxis limited to the immediate postoperative period in high-risk populations. Future work should focus on individualized risk stratification and standardized institutional protocols."

Journal • CNS Disorders • Epilepsy

Phosphodiesterase-4 Inhibition: An Experimental Approach to Overcome Drug Resistance in a Rotenone-Corneal 6 Hz Kindling Mouse Model of Drug-Resistant Epilepsy. (PubMed, Mol Neurobiol) - "Standard anti-seizure medications (ASMs) such as pregabalin, levetiracetam, carbamazepine, phenytoin, and lamotrigine were used for resistance validation. Roflumilast as PDE4 inhibitor significantly manage DRE as evidenced by reducing seizure severity, improving cognitive functions and restoring neurochemical alterations. Its ability to modulate oxidative stress and provide neuroprotection in RCK mice underscores its promise as a novel adjunct treatment for DRE."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • CAT

Predicting xenobiotic metabolism: a computational approach mining LC-MS/MS data with SIRIUS and BioTransformer. (PubMed, Arch Toxicol) - "We challenged our workflow to the analysis of human metabolites from 6 well-known drugs, administered to primary human hepatocytes and human liver microsomes: amitriptyline (10 µM), carbamazepine (12.5 µM), cyclophosphamide (20 µM), fipronil (20 µM), phenytoin (50 µM), and verapamil (6 µM). This strategy proved efficient in accelerating the study of drug metabolism, potentially avoiding tedious manual metabolite identification. In sum, we demonstrate that this computational workflow holds potential in automating metabolite identification, expanding metabolite coverage, and elucidating metabolites of newly developed drugs."

Journal

Combination of two Na+ channel-inhibiting anticonvulsants lacosamide and phenytoin: An additive, synergistic, or antagonistic effect? (PubMed, Biochem Pharmacol) - "On the other hand,the rare cardiac adverse events reported for LCM use is not expected to increase with the combination because of the little additive effect on intermediate inactivated states. Abbreviations: AUC, area-under-the-curve; ANOVA, analysis of variance; CA1, cornu ammonis area 1 of the hippocampus; CHO-K1, Chinese hamster ovary K1; CI, combination index; DPH, phenytoin; EEG, electroencephalography; FBS, fetal bovine serum; GFP, green fluorescent protein; If, fast inactivated states; Ii, intermediate inactivated states; Is, slow inactivated states; LCM, lacosamide; Nav1.7, voltage-gated sodium channel subtype 1.7; SEM, standard error of the mean."

Journal • CNS Disorders • Epilepsy • NAV1

Severe cutaneous adverse reactions linked to medications in children and adolescents: a pharmacovigilance study based on the FDA Adverse Event Reporting System database. (PubMed, Int J Clin Pharm) - "SCARs in children and adolescents show distinct patterns, high hospitalization and mortality, and strong links with antiepileptics and anti-infectives. Strengthening pediatric pharmacovigilance, implementing risk-alert systems, and promoting genotype-guided prescribing may help prevent these severe reactions."

Adverse events • Journal • Eosinophilia • Pediatrics • Steven-Johnson Syndrome

Prevalence and factors associated with seizures in tuberculous meningitis. (PubMed, Med J Malaysia) - "Seizures are common in TBM and are associated with worse clinical outcomes. Early clinical signs such as altered behaviour and focal deficits may help identify high-risk TBM patients with seizures. Seizures in TBM are associated with worse neurological outcomes. The common antiseizure therapy initiated for treatment include phenytoin, valproate and levetiracetam. Further prospective studies are needed to refine risk stratification and optimize management."

Journal • Observational data • Retrospective data • CNS Disorders • Epilepsy • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Quantifying the risk of drug-associated skin hyperpigmentation relative to the general population: A national cohort study using TriNetX. (PubMed, JAAD Int) - No abstract available

Journal

Anti-N-Methyl-D-Aspartate Receptor (Anti- NMDAR) Encephalitis in a Young Pregnant Woman With a 10-Year Follow-Up (AES 2025) - "IV methylprednisolone and IVIG were administered, but clinical progress remained minimal...She was subsequently discharged after 18 weeks of hospitalization with no further seizures, on a tapering regimen of levetiracetam, phenytoin, and prednisolone.In 2017, the patient presented at 13 weeks' gestation with a headache and a single seizure... This case highlights the diagnostic and therapeutic challenges of anti-NMDAR encephalitis during pregnancy. In this case, the disease progressed to seizures, autonomic instability, and respiratory compromise, requiring intensive management. The patient's lack of response to corticosteroids and IVIG until after spontaneous abortion underscores the potential impact of pregnancy on disease progression and treatment response"

Clinical • CNS Disorders • Epilepsy • Immunology • Obstetrics • Psychiatry

Lymphocytoma cutis treated with topical tacrolimus (ISDS 2025) - "Identified triggers include acupuncture, piercings, tattoos, medications (e.g., phenytoin), vaccinations, viral infections, insect bites, and Borrelia burgdorferi, though many cases are idiopathic...Current treatments—including systemic corticosteroids, intralesional injections, superficial radiotherapy, PUVA, photodynamic therapy, cryosurgery, and hydroxychloroquine—show variable efficacy, with no consensus on optimal management... This case highlights the potential utility of topical tacrolimus in LC, expanding therapeutic options for this challenging condition. Given the limited data on tacrolimus use in LC, further studies are warranted to establish efficacy and safety, particularly for lesions in cosmetically sensitive areas."

CNS Disorders • Dermatology • Hematological Malignancies • Infectious Disease • Lyme Disease • Lymphoma • Pruritus

Variations between package inserts regarding gingival overgrowth causing drugs. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Despite the lower number of prescriptions, significantly more cases of DIGO must be expected with valproic acid therapy than with amlodipine or phenytoin, for example...As a source of information for healthcare professionals, the SmPC unfortunately does not provide any detailed information on DIGO. In patients receiving long-term therapy with valproic acid, particular attention must be paid to the development of DIGO to initiate therapy at an early stage."

Journal

Streptozocin-Induced Diabetes Mellitus Facilitates Longitudinal Changes In Gray And White Matter Microstructure, And Increased Susceptibility To Status Epilepticus In Rats (AES 2025) - "Finally, all the animals received 3-mercaptopropionic acid (MP) every 12 h for 5 days to induce recurrent generalized seizures, followed by a crossed protocol with phenytoin for 4 days to assess pharmacorresistance. This induction was considered indicative of high seizure severity, potentially attributable in part to hippocampal alterations (neuronal loss, gliosis) and reduced fractional anisotropy in specific brain regions, likely reflecting axonal degeneration."

Preclinical • CNS Disorders • Diabetes • Epilepsy • Metabolic Disorders • Type 2 Diabetes Mellitus

Predictive Role of Neuroinflammation on Anti-Seizure Medication Response and Seizure Localization in Epilepsy: A Bioinformatics and Machine Learning Approach (AES 2025) - "These immune cell infiltration patterns were not observed in carbamazepine or phenytoin subgroups. Our findings reveal that neuroinflammation influences both treatment response and seizure localization in epilepsy. Valproate responders showed distinct immune suppression suggesting inflammation status could guide therapy selection. These results highlight that neuroinflammation can be used as a potential predictive biomarker and a potential target for tailoring valproate use or immunomodulatory treatment."

Machine learning • CNS Disorders • Epilepsy • Inflammation • CD4 • CD69 • CD8 • HLA-C • PACERR • PTGS2

Cenobamate and Brivaracetam Use in Pregnancy and Lactation - A Case Report (AES 2025) - "She previously failed multiple ASMs, including clonazepam, gabapentin, oxcarbazepine, levetiracetam, lamotrigine, zonisamide, and phenytoin, due to inadequate seizure control or intolerable side effects. This case describes a normal pregnancy outcome in a young female with intractable localization-related epilepsy on combination cenobamate and brivaracetam. To our knowledge, this is the first reported pregnancy outcome with this specific ASM combination. This offers reassuring, preliminary evidence that cenobamate and brivaracetam may be safely continued in pregnancy when benefits outweigh risks, especially in intractable epilepsy."

Case report • Clinical • Anesthesia • CNS Disorders • Epilepsy

A Drug-Drug Interaction Study of EPX-100 (Clemizole Hydrochloride) With Clinical Probe Substrates for Selected CYP Enzymes (AES 2025) - P3 | "Each part was designed as a 2-period fixed sequence, with Parts 1 and 2 involving administration of a single oral 80-mg dose of EPX-100 on Day 1 (Period 1), followed in Period 2 by either 200-mg oral itraconazole twice daily for 1 day followed by 200-mg oral itraconazole once daily for 4 days (Part 1), or 100-mg oral phenytoin 3 times daily for 14 days (Part 2)...During Period 2, 80-mg twice-daily doses of EPX-100 were administered for 18 days with a single oral dose of 40-mg omeprazole, 2-mg midazolam, or 100-mg bupropion on Days 12, 14, and 15, respectively... The drug-drug interaction profile with EPX-100 has been evaluated, and final results will be presented. EPX-100 was generally safe and well tolerated in this study of healthy participants. Findings from this study will inform other studies of EPX‑100, including the currently enrolling ARGUS study for DS (NCT04462770) and the LIGHTHOUSE study for LGS (NCT05066217)."

Clinical • CNS Disorders • Epilepsy • CYP2C19 • CYP3A4

A Rare Case of Adult-Onset Lennox-Gastaut Syndrome and possible association with Retinitis Pigmentosa (AES 2025) - "After a month, she was readmitted for breakthrough seizures which progressed to status epilepticus and her epilepsy became intractable, necessitating her to be on multiple antiseizure medications including phenytoin, clobazam, rufinamide, valproic acid, levetiracetam, and topiramate. This is an unusual case of late onset LGS that manifested in adulthood and rapidly became medically intractable. It was associated with simultaneous development of ophthalmologic findings suggestive of retinitis pigmentosa. Adult onset LGS has only been described in 3 cases in the literature."

Clinical • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Cannabidiol Inhibits Phenytoin Clearance and Can Result in Clinical Changes (AES 2025) - "A CBD interaction has been well documented for patients taking clobazam (CLB) but not for PHT...On presentation, he was taking levetiracetam, clonazepam, and PHT (which mom reported minimized the frequency and severity of his tonic-clonic seizures)...Epidiolex (CBD) was initiated according to the standard titration... These two cases show CBD inhibition of PHT metabolism can lead to significant increases in levels and meaningful clinical changes (in one case sz control and in the other drug toxicity). In case 1, clinical benefit may also relate to the increase in CLB metabolite and direct effect of CBD. However, the recurrence of seizures on lowering the PHT dose and the resumption of improved control once PHT was restored suggests the elevated PHT was most significant."

Clinical • Late-breaking abstract • Ataxia • CNS Disorders • Epilepsy • Movement Disorders • Ophthalmology • CYP2C19

Hidden in Decline: Epilepsy in Neurodegenerative Disorders and the Case for Integrated Care (AES 2025) - "ASMs such as levetiracetam and lamotrigine have shown promise in controlling seizures while preserving cognition, suggesting dual therapeutic potential. Older ASMs (e.g., phenytoin, valproate) are linked to cognitive decline, metabolic effects, and valproate-induced parkinsonism... Integrated diagnostic and therapeutic approaches are critical to address the burden of epilepsy in NDDs. Future research should prioritize: (1) implementing standardized seizure screening in NDDs to reduce misattribution of seizures to disease progression, (2) characterizing the bidirectional influence of epilepsy and neurodegeneration on cognition, (3) identifying safe and effective ASMs, and (4) developing disease-modifying therapies addressing shared mechanisms. Device-based therapies (e.g., vagus nerve stimulation, responsive neurostimulation, deep brain stimulation) and dietary approaches (e.g., ketogenic therapy) also warrant evaluation."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Frontotemporal Lobar Degeneration • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Using Seizure Dynamotypes to Predict Response to Antiseizure Medications (AES 2025) - "Also: Undergraduate Research Opportunities Program at the University of Utah, NIH NINDS: F32 NS114322 awarded to Daria Anderson and University of Utah Skaggs Fellowship awarded to Ashley Zachery-Savella Rationale: Epilepsy treatment is complicated by the fact that patients with similar phenotypes and seizure classifications do not respond similarly to the same treatments, suggesting subtler differences exist that cannot be accounted for by our currently-limited classification system... We analyzed seizure frequency and dynamotype in six treatment cohorts: 294 seizures/21 animals in the carbamazepine (30 mg/kg, t.i.d.) cohort, 820 seizures/17 animals in the phenobarbital (PB, 50 mg/kg, b.i.d.) cohort, 848 seizures/22 animals in the valproate (VPA, 240 mg/kg, t.i.d.) cohort, and 825 seizures/21 animals in the phenytoin (PHT, 20 mg/kg, b.i.d.) cohort... Dynamotype analysis reveals drug-specific modulation of seizure onset and offset patterns. PHT did not reduce seizure..."

CNS Disorders • Epilepsy

Prolonged Rhythmic Mid-Temporal Theta of Drowsiness in a patient with Postural Orthostatic Tachycardia Syndrome, A Case of Misdiagnosis (AES 2025) - "We demonstrated that RMTD can occur at awake and light sleep state, can be prolonged up to 2 minutes. The atypical prolonged RMTD might be misdiagnosed as epileptiform discharges or electrographic seizures in certain clinical presentation, such as POTS."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Urinary Incontinence • Urology

Complementary Antisense Oligonucleotide Treatment and Precision Sodium Channel Modulation for Early Onset SCN2A DEE: Emergency Use Cases in a Preterm Infant with Refractory Status Epilepticus (AES 2025) - "Seizure frequency remained stable with ongoing dosing; maintained after tapering phenytoin at 14 months, with no neurodevelopmental worsening. Preliminary first-in-human findings highlight the potential for complementary use of elsunersen and relutrigine for early onset SCN2A DEE, which we hypothesize is due to targeting both the root genetic cause and downstream network hyperexcitability characteristic of this disease."

Clinical • Prematurity • CNS Disorders • Developmental Disorders • Epilepsy

Optimizing Initial Seizure Treatment in Older Adults: A Retrospective Cohort Study in Medicare Linked to the Health and Retirement Study (AES 2025) - "The five most commonly prescribed ASMs were: levetiracetam (27%), lorazepam (15%), phenytoin (12.6%), gabapentin (11.4%) and pregabalin (9.9%). When epilepsy is diagnosed in older adults, they are often prescribed ASMs that have known adverse effects as initial therapy for epilepsy. However, ASMs recommended by the American Epilepsy Society and American Academy of Neurology guidelines for initial therapy are associated with longer persistence, which may suggest they are more effective or cause fewer side effects."

Medicare • Reimbursement • Retrospective data • US reimbursement • CNS Disorders • Epilepsy

Ictal Asystole and Suspected Concurrent Sick Sinus Syndrome in an Elderly Patient with Longstanding Focal Epilepsy: A Diagnostic and Management Challenge (AES 2025) - "In older adults, distinguishing seizure-related cardiac pauses from primary conduction abnormalities is essential to prevent injury, guide treatment, and detrimental outcomes. We report a unique case with possible concurrent IA and intrinsic SSS. A 61-year-old woman with epilepsy since age 16, previously well-controlled on phenytoin, experienced infrequent focal impaired awareness seizures (FIAS), averaging 3–4 per year... IA is thought to result from seizure propagation to central autonomic structures—particularly the insula, amygdala, and medial prefrontal cortex—leading to heightened parasympathetic output and transient cardiac inhibition. IA typically manifests after electrographic seizure onset and resolves spontaneously. In contrast, SSS reflects intrinsic sinoatrial node dysfunction, causing spontaneous bradyarrhythmias or pauses independent of ictal activity."

Clinical • Cardiovascular • CNS Disorders • Epilepsy