What is the recommended dose of perampanel (perampanel) for pediatric patients with focal seizures?

Recommended Dosing of Perampanel for Pediatric Patients with Focal Seizures

For pediatric patients with focal seizures, perampanel should be initiated at 2 mg once daily at bedtime, with dose increases of 2 mg weekly based on clinical response and tolerability, to a recommended maintenance dose range of 8-12 mg once daily. 1

Initial Dosing and Titration

• The FDA-approved starting dose for perampanel in children 4 years and older with focal-onset seizures is 2 mg once daily taken orally at bedtime 1
• Dose increases should occur no more frequently than at weekly intervals, with increments of 2 mg once daily 1
• Titration should be based on individual clinical response and tolerability 1

Maintenance Dosing

• The recommended maintenance dose range is 8 mg to 12 mg once daily 1
• Some patients may respond adequately to a dose of 4 mg daily 1
• A dose of 12 mg once daily may result in somewhat greater seizure reduction than 8 mg daily, but with substantially more adverse effects 1, 2
• In real-world studies, many pediatric patients achieve good seizure control at lower doses (4-8 mg/day) 2

Special Considerations

Concomitant Enzyme-Inducing Medications

• When perampanel is used with moderate or strong CYP3A4 enzyme inducers (including antiepileptic drugs such as phenytoin, carbamazepine, and oxcarbazepine):
  • Starting dose should be increased to 4 mg once daily at bedtime 1
  • Dose increases should still occur in 2 mg increments no more frequently than weekly 1
  • Higher doses may be required to achieve therapeutic effect due to reduced plasma levels 1, 3

Hepatic Impairment

• For patients with mild hepatic impairment:
  • Start with 2 mg once daily
  • Increase by 2 mg increments no more frequently than every 2 weeks
  • Maximum recommended dose is 6 mg daily 1
• For patients with moderate hepatic impairment:
  • Start with 2 mg once daily
  • Increase by 2 mg increments no more frequently than every 2 weeks
  • Maximum recommended dose is 4 mg daily 1
• Perampanel is not recommended for patients with severe hepatic impairment 1

Age-Specific Considerations

• Perampanel is FDA-approved for focal seizures in patients 4 years of age and older 1
• Clinical trials have demonstrated efficacy and safety in children aged 4 to <12 years with focal seizures, with a mean daily dose of 7.0 mg 4
• Adolescents may experience more behavioral adverse events than adults 3

Safety and Monitoring

• Most common adverse events include somnolence (26%), dizziness, and nasopharyngitis 4
• Serious psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation have been reported 1
• Adverse events occur more frequently during the titration period (60.2%) than during maintenance (28.4%) 2
• Close monitoring is particularly important during the titration period and at higher doses 1
• If serious behavioral symptoms occur, dose reduction is recommended; discontinue immediately if symptoms are severe or worsening 1
• Patients with pre-existing behavioral comorbidities may be at higher risk for behavioral adverse events 3

Clinical Efficacy

• In clinical studies, perampanel has demonstrated efficacy as adjunctive therapy for focal seizures in pediatric patients:
  • Median percent reduction in seizure frequency of 40% for focal seizures 4
  • 50% responder rate of 47% for focal seizures 4
  • Seizure freedom rate of 12% for focal seizures 4
• Efficacy appears consistent regardless of age group (4 to <7 years or 7 to <12 years) 4

Practical Considerations

• Once-daily dosing is possible due to perampanel's long half-life 3
• Decreasing the dose frequently resolves adverse events without complete discontinuation 3
• The medication can be administered as an oral suspension for younger children 4