10/16/2020 Highlights Michigan State Medical Society Annual Scientific Meeting 10/23/2020 Seizures and Epilepsy in Non-Neurologic Specialties: . Why more new seizure medications? Newer Anti-Seizure Medications . The newer AEDs, their MOA, advantages, disadvantages, and SE . Any other new option beside medications? Mounzer Kassab, M.D., M.A. Professor and Vice Chairman Department of Neurology Michigan State University Sparrow Health System 1 2 Oxcarbazepine Zonisamide Why Newer AEDs? Levetiracetam Some FDA approved Available AEDs Pregabalin Still no magic pill for epilepsy Lacosamide Clobazam Still SE and drug-drug-interaction Aptiom Fycompa Still inconveniences in administration and preparations Potiga 10 topiramate Targets for newer AEDs: tiagabine lamotrigine gabapentin Better efficacy?? felbamate Less SE and drug-drug interactions valproate 5 carbamazepine More friendly with better titration schedule, administration routs, and preparations ethosuximide phenytoin phenobarbital 1900 1920 1940 1960 1980 2000 3 4 The problem: brivaracetam “Briviact” . Seizure freedom: . MOA: selective affinity for the target synaptic vesicle protein 2A. The . After first AED: 47% selectivity exclude AMPA receptors = less irritability SE . After second AED 13% . Dosing: initial dosage is 25mg or 50mg twice daily. Target dose is 100mg . After third AED 3% twice daily . Metabolism: in blood, renal excretion. Adv: Renal failure . SE: somnolence, dizziness and fatigue. Adv: No labs for toxicity . Formulations: pills, oral solution, IV injection solution 5 6 1 10/16/2020 cenobamate (Xcopri) Nasal Sprays • MOA: inhibiting voltage-gated sodium currents and is a positive allosteric Seizure Clusters.. modulator of the γ-aminobutyric acid (GABAA) ion channel • SE: somnolence, dizziness, fatigue, diplopia, and headaches. • Dosage • Week 1 and 2: 12.5 mg once daily • Week 3 and 4: 25 mg once daily • Week 5 and 6: 50 mg once daily • Week 7 and 8: 100 mg once daily • Week 9 and 10: 150 mg once daily • Week 11 and thereafter 200 mg once daily 7 8 Nasal Spray midazolam (Nayzilam) Nasal Spray diazepam (Valtoco) • MOA and indications: Is a benzodiazepine indicated for the acute treatment of acute repetitive seizures that are distinct from the patient’s usual seizure pattern . MOA and indications: is a benzodiazepine for the acute treatment of • No priming or assembly necessary intermittent frequent clusters of seizures. • Can be administered by almost anyone . Dose: 5, 10, 15, or 20 mg based on weight. Second dose may be given • SE: Somnolence and nasal discomfort no sooner than 4 hours after the first dose if needed. • Dose: one spray (5mg) into one nostril. If needed after 10 minutes, one spray (5mg) can be administered in the other nostril. SE: nasal discomfort, epistaxis, cough, throat irritation somnolence in 1.5 to 5% of subjects 9 10 Other new options in treatment? . Resective surgery . VNS . RNS . DBS . Diet 11 2.