perampanel and Fatigue

To investigate the safety of perampanel in different disorders and doses.. Embase, the Cochrane Library, Medline, and ClinicalTrials.gov were searched from inception to July 2022 for randomized controlled trials (RCTs). The meta-analysis was performed by using Review Manager 5.3 and R 4.2.1 software.. A total of 17 RCTs with 5711 subjects were included in the final analysis. The double-blind treatment phase was from 12 weeks to 48 weeks. Our results showed that 11 adverse events (aggression, ataxia, balance disorder, dizziness, fall, fatigue, irritability, rash, somnolence, vertigo, and weight increase) were statistically significantly associated with perampanel, and 4 of them (ataxia, dizziness, fatigue, and somnolence) showed a clear dose-response relationship. Psychiatric adverse events occurred most frequently among serious treatment-emergent adverse events (TEAEs). At 8 mg/day, seven adverse events (aggression, balance disorder, dizziness, fatigue, irritability, vertigo, and weight increase) occurred more frequently in patients with epilepsy than in patients with other disorders, whereas dose discontinuation rates due to adverse events were lower in patients with epilepsy than in patients with other disorders.. The safety profile of perampanel is dependent on diseases and dose. The risk of adverse events was statistically significantly higher, with doses exceeding 4 mg/day. Despite a higher risk of adverse events, patients with epilepsy had a lower perampanel discontinuation rate than patients with other disorders.

Topics: Anticonvulsants; Ataxia; Dizziness; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Fatigue; Humans; Pyridones; Randomized Controlled Trials as Topic; Sleepiness; Treatment Outcome; Vertigo

Evaluate the impact of concomitant enzyme (CYP3A4)-inducer antiepileptic drugs (EIAEDs) on the efficacy and safety of perampanel in patients from the 3 phase-III clinical trials.. Patients with pharmacoresistant partial-onset seizures in the 3 phase-III clinical studies were aged 12 years and older and receiving 1 to 3 concomitant antiepileptic drugs. Following 6-week baseline, patients were randomized to once-daily, double-blind treatment with placebo or perampanel 8 or 12 mg (studies 304 and 305) or placebo or perampanel 2, 4, or 8 mg (study 306).. Treatment response assessed by median percent reduction in seizure frequency and responder rates improved with perampanel compared with placebo. However, at 8 and 12 mg, the treatment response was significantly greater in patients receiving non-EIAEDs. The treatment effect (perampanel-placebo) also demonstrated a dose-dependent increase in all patients. The overall incidence of treatment-emergent adverse events was similar regardless of the presence of EIAEDs. Occurrence of some adverse events, such as fatigue, somnolence, dizziness, irritability, was greater in patients receiving non-EIAEDs, as was discontinuation because of adverse events.. Perampanel shows efficacy and safety in the presence and absence of EIAEDs. As systemic exposure to perampanel increases, so does efficacy. Given the extensive metabolism of perampanel, systemic exposure is clearly reduced with concomitant administration of CYP3A4 inducers. This supports the strategy of dosing perampanel to clinical effect. Recognition of these pharmacokinetic interactions will be important in the optimization of this novel medication.. This study provides Class II evidence that 2 to 12 mg/d doses of perampanel reduced seizure frequency and improved responder rate in the presence and absence of EIAEDs.

Topics: Adult; Anticonvulsants; Cytochrome P-450 CYP3A Inducers; Disorders of Excessive Somnolence; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Interactions; Epilepsy; Fatigue; Female; Humans; Internationality; Male; Mental Disorders; Nitriles; Pyridones; Treatment Outcome

There is no pediatric overdose information available for perampanel. We present twocases involving children 2 years of age. A female ingested 0.77mg/kg perampanel anddeveloped drowsiness and ataxia within an hour, followed by bradycardia after 6 hours.She was admitted to the pediatric intensive care unit and given fluids and was thendischarged after 20 hours. The other case involved a male who ingested 0.25mg/kgperampanel and developed ataxia within an hour, eventually he was discharged after 6hour observation in the emergency department without any treatment.

Topics: Anticonvulsants; Ataxia; Bradycardia; Child, Preschool; Drug Overdose; Fatigue; Female; Humans; Male; Nitriles; Pyridones

Perampanel is an AMPA receptor antagonist recently approved for the treatment of partial and generalized epilepsies with tonic-clonic seizures as an add-on therapy.. This single-center postmarketing study retrospectively evaluated the efficacy of perampanel in patients with partial onset and other seizure types, with a special emphasis on its efficacy, safety, and tolerability.. Review of medical records revealed that adequate data were available on 101 patients taking perampanel. Fifty-seven patients were female. Sixteen patients were of pediatric age range. The average dose of perampanel was 6.5mg, and average treatment duration was 8.2months. After treatment, median seizure frequency reduction was 50% overall, 50% in children, and 33% in adults; 44% in primary generalized, 38% in secondarily generalized, and 33% in partial seizures. Responder rate (50% seizure frequency reduction) was 51% overall, 63% in children, and 49% in adults; 60% in partial seizures, 43% in secondarily generalized tonic-clonic seizures, 53% in primary generalized tonic-clonic seizures, and 56% in other seizure types. Seizure freedom was attained in 6% of cases. Most common adverse events were sleepiness/fatigue (35%), behavioral problems (30%), and dizziness (22%). Adverse events were correlated with dosage. Average dose was 7.3mg in patients with adverse events vs. 5.5mg in those without adverse events. Patients who developed fatigue, cognitive decline, headaches, and weight gain were more likely to discontinue perampanel than those patients who experienced coordination issues and behavioral problems.. These findings suggest that perampanel is safe, well-tolerated, and effective in treatment of various types of adult and pediatric epilepsy syndromes. Fatigue, cognitive decline, headache and weight gain were the main causes of perampanel discontinuation.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Fatigue; Female; Humans; Infant; Male; Middle Aged; Nitriles; Product Surveillance, Postmarketing; Pyridones; Receptors, AMPA; Retrospective Studies; Safety; Seizures; Treatment Outcome; Young Adult