Management Of Partial-onset Seizures Research Articles

Cenobamate (Xcopri)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses cenobamate (Xcopri), 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg tablet, oral.
 Indication: As adjunctive therapy in the management of partial onset seizures in adults with epilepsy who are not satisfactorily controlled with conventional therapy.

Cenobamate (Xcopri)


 CADTH recommends that Xcopri should be reimbursed by public drug plans as adjunctive therapy in the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, if certain conditions are met.
 Xcopri should only be reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, according to the criteria used by the public drug plans for other third generation antiseizure medication (ASMs) that are currently reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy.
 Xcopri should only be reimbursed if the daily cost of Xcopri is the same as or lower than the daily cost of other third generation adjunctive therapies (lacosamide, brivaracetam, eslicarbazepine, and perampanel), and if the potential budget impact of funding Xcopri is addressed.

Behavioral And Psychiatric Adverse Events Induced By Brivaracetam: A Case Report

Background: Brivaracetam (BRV) is an anti-convulsant belonging to third-generation antiepileptic and approved by FDA as an add-on therapy as well as monotherapy for management of partial onset seizures in both adults and pediatrics as young as 1 month of age. Brivaracetam induces psychiatric adverse reactions, including non-psychotic and psychotic symptoms. Case Report: A 26-year-old male patient having a past medical history of dyslexia was diagnosed with Seizure disorder during February 2021. Initially, the patient was prescribed Levetiracetam 500 mg BD to control his seizure. The drug was well tolerated and there were no episodes of seizure for a period of 6 months. In August 2021, the patient had a recurrence of convulsions. As a consequence, Brivaracetam 50mg BD and Sodium Valproate 500mg BD were prescribed. The patient gradually started exhibiting unusual behavioral and psychiatric adverse events. The reaction was primarily ascribable to brivaracetam based on the temporal association between non-contributable disease and co-medication. The WHO causality assessment scale graded the ADR to be ‘probable’ and Naranjo’s algorithm with a score of 6. The physician recommended discontinuation of Brivaracetam and advised to continue Sodium Valproate 500mg BD, while Clobazam 5mg BD was added to patient treatment regimen. The patient’s symptoms progressively alleviated, and his behavior returned to normal within one week of discontinuing the Brivaracetam. Conclusion: When initiating treatment with Brivaracetam, close clinical assessment and monitoring is required and recommended to identify any behavioral and psychiatric adverse effects to achieve optimum treatment outcome.

Eslicarbazepine acetate for the treatment of partial epilepsy

ABSTRACTIntroduction: Eslicarbazepine acetate (ESL) is a third generation AED structurally related to carbamazepine and oxcarbazepine, but without several of the drawbacks associated with these compounds. ESL is completely metabolized to its eslicarbazpine, which selectively binds inactivated voltage-gated sodium channels and thus selectively reduces the activity of rapidly firing (epileptic) neurons. In addition, ESL has pharmacokinetic properties allowing once daily dosing.Areas covered: This review summarizes data from the initial phase I to III studies, which demonstrated efficacy of ESL as add-on treatment in partial onset epilepsy, and more recent studies that demonstrate efficacy of ESL as monotherapy. Real-life observational studies are also reviewed, and seem to confirm the notion of ESL as a well-tolerated AED. As a new AED, ESL needs to be subject to close monitoring regarding long-term adverse events. Future independent studies will most likely clarify the role of ESL in the management of partial onset seizures.Expert opinion: The role of ESL in management of partial onset seizures is discussed, as is the need for close monitoring and evaluation for broad-spectrum pharmacodynamics properties. The characteristics of the molecule and efficacy and safety profiles seem, however, very promising.

Levetiracetam (Keppra): Evidence-Based Polypharmacy in Two Patients With Epilepsy

Introduction: Epilepsy is a prolonged disorder characterized by repeated violent epileptic seizures. Its managements depend on proper classification of the seizure category and the epileptic pattern. Levetiracetam (Keppra®) has been approved as monotherapy or for adjunctive management of partial onset seizures, juvenile myoclonic epilepsy, and idiopathic generalized epilepsy. Case re- porting of levetiracetam polypharmacy shows adverse eects linked to evidence-based clinical and laboratory data in two patients with epilepsy. Case reporting of levetiracetam polypharmacy, based on evidence-based clinical and laboratory data was of interest that investigated. Case Presentation: Two cases were studied, one patient was a 32-year-old male and the other was a 14-year-old female. The key words relevant to search topics were surveyed using PubMed (United States national library of medicine). Articles related to the levetiracetam prescription in epileptic patients were selected and considered separately. Pharmacotherapy based on levetiracetam, primidone, phenytoin, and topiramate in a 32-year-old epileptic male showed a decrease in white blood cell count (3400 cells/mcL), red blood cell count (4.4 mil/mm 3 ) hemoglobin (11.8 g/dL) and hematocrit (36.7%). The drug regimen for the 14-year-old epileptic female was a levetiracetam polypharmacy in combination with primidone and sodium-valproate simultaneously. In this patient, there was a decrease in hemoglobin (10.4 g/dL) and hematocrit (34%). An increase in lymphocyte (84%) was also observed. Conclusions: Administration of AEDs in general and levetiracetam in particular should be based on attention to pharmacokinetic behavior in terms of monotherapy or polypharmacy.

Perampanel in the management of partial-onset seizures: a review of safety, efficacy, and patient acceptability.

Perampanel (PER) is a novel antiepileptic drug recently introduced for the adjunctive treatment in epilepsy patients aged 12 years or older with partial-onset seizures with or without secondary generalization in the US and Europe. Its antiepileptic action is based on noncompetitive inhibition of postsynaptic AMPA receptors, decreasing excitatory synaptic transmission. Evaluation of efficacy in three placebo-controlled randomized Phase III studies showed that add-on therapy of PER decreased seizure frequencies significantly compared to placebo at daily doses between 4 mg/day and 12 mg/day. PER’s long half-life of 105 hours allows for once-daily dosing that is favorable for patient compliance with intake. Long-term extension studies showed a 62.5%–69.6% adherence of patients after 1 year of treatment, comparing favorably with other second-generation antiepileptic drugs. Whereas these trials demonstrated an overall favorable tolerability profile of PER, nonspecific central nervous system adverse effects like somnolence, dizziness, headache, and fatigue may occur. In addition, neuropsychiatric disturbances ranging from irritability to suicidality were reported in several case reports; both placebo-controlled and prospective long-term extension trials showed a low incidence of such behavioral and psychiatric complaints. For early recognition of neuropsychiatric symptoms like depression, anxiety, and aggression, slow titration and close monitoring during drug introduction are mandatory. This allows on the one hand to recognize patients particularly susceptible to adverse effects of the drug, and on the other hand to render the drug’s full potential of seizure control available for the vast majority of patient groups tolerating the drug well.

A review of the efficacy and safety of eslicarbazepine acetate in the management of partial-onset seizures.

Eslicarbazepine acetate is a is a once-daily antiepileptic drug (AED) that was approved in 2009 by the European Medicines Agency (EMA) (Zebinix™), and in 2013 by the US Food and Drug Administration (FDA) (Aptiom™) as adjunctive therapy in adults with refractory partial-onset seizures, with or without secondary generalization. It is a third-generation member of the dibenzazepine family of AEDs with distinctive mechanism of action, posology and tolerability profile. The eslicarbazepine acetate development program included an initial phase II study (study BIA 2-093) and three subsequent phase III, multicentre, randomized, double-blinded and placebo-controlled clinical trials (studies BIA-2093-301, BIA- 2093-302 and BIA -2093-303). A fourth phase III placebo-controlled trial (study BIA-2093-304) was designed in order to meet specific requirements of the FDA. All performed studies have consistently shown that eslicarbazepine acetate (800 to 1200 mg/day) is effective and well tolerated as adjunctive therapy for adults with partial-onset seizures.

Lacosamide: A Review of Its Use as Adjunctive Therapy in the Management of Partial-Onset Seizures

Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet) and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in several countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures; however, prescribing regulations differ between countries. This article reviews the use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where it is approved in this patient population as an adjunctive therapy to other AEDs in the treatment of partial-onset seizures, with or without secondary generalization. In three randomized, double-blind, placebo-controlled, multicentre studies in adults and adolescents (aged 16-18 years) with partial-onset seizures, adjunctive therapy with oral lacosamide (administered for an initial titration period followed by 12 weeks' maintenance therapy) generally reduced the frequency of seizures to a significantly greater extent than placebo, with antiepileptic efficacy sustained following longer-term treatment (up to 8 years) in this patient population. Oral and intravenous lacosamide were generally well tolerated in clinical studies, with the majority of adverse events being mild or moderate in severity. Very common adverse reactions following adjunctive therapy with oral lacosamide included diplopia, dizziness, headache and nausea; the tolerability profile of intravenous lacosamide appeared consistent with that of oral lacosamide, although intravenous administration was associated with local adverse events, such as injection site discomfort or pain, irritation and erythema. Thus, oral and intravenous lacosamide as an adjunctive therapy to other AEDs provides a useful option in the treatment of patients with partial-onset seizures.

Ezogabine: Development and Role in the Management of Epileptic Seizures

Epilepsy which is a diverse set of complex neurological disorders comprised of seizures affecting more than 50 million people worldwide among which 90 % are from developing countries. The aim of current antiepileptic therapy is to control the seizures with minimal side effects and improve the patients' quality of life. Near by about 20 medications are approved by Food and Drug Administration among which only five to six are widely used for the treatment of epileptic seizures. Ezogabine (D-23129) is a recently approved antiepileptic drug approved by USFDA for adjunctive therapy of partial onset seizures. It was developed by Valeant Pharmaceuticals and Glaxosmithkline in 2011 for the management of partial onset seizures. The drug has shown unique mechanism of action among other antiepileptic drugs by facilitating potassium channel current in nerve growth factor differentiated PC12 cells. It also promotes membrane repolarisation and thus opposes rapid repetitive discharges. The drug is quickly absorbed and reaches maximum plasma concentration between 0.5 hour and 2 hours after a single oral dose also showing a moderately high bioavailability, volume of distribution and a terminal half life of 8 to 11 hours. It is metabolized via glucuronidation and acetylation. The various adverse effects found with the drug were related to central nervous system and appeared to be dose related like drowsiness, dizziness, vertigo and confusion etc. All these parameters make it superior from other available drugs for the management of epileptic seizures. The present review describes the development; medicinal chemistry; mechanism of action, pharmacokinetics and pharmacodynamics of Ezogabine. Further the review put forwards the indispensible role of this drug for antiepileptic treatment.

Levetiracetam. A review of its adjunctive use in the management of partial onset seizures.

Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is approved for use as adjunctive therapy in adult patients with partial onset seizures. Oral levetiracetam 1000, 2000 and 3000 mg/day administered as adjunctive therapy for up to 18 weeks significantly increased responder rates and reduced seizure frequency compared with placebo in 3 well designed pivotal trials in adults with treatment-refractory partial seizures with or without secondary generalisation. Levetiracetam 3000 mg/day also significantly increased the number of seizure-free patients, but the effects of levetiracetam 1000 and 2000 mg/day on this end-point were unclear. Effects on seizure severity were not assessed in these trials. Although not yet approved as monotherapy or for use in paediatric patients, efficacy was observed with levetiracetam 3000 mg/day as monotherapy in adult patients with refractory partial seizures with or without secondary generalisation and with the 10 to 40 mg/kg/day dosage as adjunctive therapy in children with refractory partial seizures. However, these data are limited. Oral levetiracetam 1000, 2000 and 3000 mg/day as adjunctive therapy is generally well tolerated with an overall incidence of adverse events similar to that observed with placebo. The most commonly reported events in individual clinical trials were CNS-related and included somnolence, asthenia, headache and dizziness. Levetiracetam administered as adjunctive therapy does not appear to interact with other anticonvulsant drugs, and no clinically relevant interactions were observed between levetiracetam and digoxin, warfarin or probenecid; oral contraceptive protective efficacy was also not affected by levetiracetam. Levetiracetam is a new anticonvulsant agent with a favourable tolerability profile and a low potential for drug interactions. It has shown efficacy as adjunctive therapy in patients with treatment-refractory partial onset seizures with or without secondary generalisation in clinical trials. Direct comparative trials with other anticonvulsant agents are not yet available, but placebo-controlled clinical evidence to date suggests that levetiracetam (1000, 2000 and 3000 mg/day) is a useful option as adjunctive therapy in patients with this subtype of epilepsy.