Fycompa (perampanel)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved October 2012

Specific Treatments:

partial-onset seizures with or without secondarily generalized seizures; tonic-clonic seizures

General Information

Fycompa (perampanel) is a selective AMPA-type glutamate receptor antagonist. The AMPA receptor is widely present most excitatory neuronal synapses and plays a role in a large number of central nervous system diseases.

Fycompa is specifically indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 4 years of age and older and as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

Fycompa is supplied as a tablet for oral administration or as an oral suspension. The recommended dose is a follows:

Dosage for Partial-Onset Seizures: 

Monotherapy or Adjunctive Therapy: The recommended starting dosage of Fycompa in adults and pediatric patients 4 years of age and older is 2 mg once daily taken orally at bedtime. Increase dosage no more frequently than at weekly intervals by increments of 2 mg once daily based on individual clinical response and tolerability.

The recommended maintenance dose range is 8 mg to 12 mg once daily, although some patients may respond to a dose of 4 mg daily. A dose of 12 mg once daily resulted in somewhat greater reductions in seizure rates than the dose of 8 mg once daily, but with a substantial increase in adverse reactions.

Dosage adjustment is recommended with concomitant use of moderate or strong CYP3A4 enzyme inducing drugs, which include certain antiepileptic drugs (AEDs). Please see drug label for specific instructions.

Dosage for Primary Generalized Tonic-Clonic Seizures: 

Adjunctive Therapy The recommended starting dosage of Fycompa in adults and pediatric patients 12 years of age and older is 2 mg once daily taken orally at bedtime. Increase dosage no more frequently than at weekly intervals by increments of 2 mg once daily based on individual clinical response and tolerability.

The recommended maintenance dose is 8 mg once daily taken at bedtime. Patients who are tolerating Fycompa at 8 mg once daily and require further reduction of seizures may benefit from a dose increase up to 12 mg once daily if tolerated.

Dosage adjustment is recommended with concomitant use of moderate or strong CYP3A4 enzyme inducing drugs, which include certain AEDs. Please see drug label for specific instructions.

Clinical Results

FDA Approval

Partial-Onset Seizures: The FDA approval was based on three randomized, double-blind, placebo-controlled, multicenter trials (Studies 1, 2, and 3) in 1,037 adults and adolescents aged 12 years and older. All trials had an initial 6-week baseline period, during which patients were required to have more than five seizures in order to be randomized. This was followed by a 19 week treatment period consisting of a 6 week titration phase and a 13 week maintenance phase. The median baseline seizure frequency ranged from 9.3 to 14.3 seizures per 28 days. The primary endpoint was the percent change in seizure frequency per 28 days during the treatment period as compared to the baseline period. A statistically significant decrease in seizure rate was observed at doses of 4 to 12 mg per day. Dose response was apparent at 4 to 8 mg with little additional reduction in frequency at 12 mg per day. For combined data, the percentages of patients with a 40 to <60% reduction in seizure frequency were 13.2%, 17.4%, 19.0%, and 15.8% for placebo, 4, 8, and 12 mg, respectively. The percentages of patients with a 50% or greater reduction in seizure frequency were 19.3%, 28.5%, 35.3%, 35.0% for placebo, 4, 8, and 12 mg, respectively.

Primary Generalized Tonic-Clonic (PGTC) Seizures: The FDA approval of Fycompa as adjunctive therapy in patients 12 years of age and older with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures was based on one multicenter, randomized, double blind, placebo-controlled study (Study 4), conducted at 78 sites in 16 countries. Eligible patients on a stable dose of 1 to 3 AEDs experiencing at least 3 primary generalized tonic-clonic seizures during the 8-week baseline period were randomized to either Fycompa or placebo. Efficacy was analyzed in 162 patients (Fycompa N=81, placebo N=81) who received medication and at least one post-treatment seizure assessment. Patients were titrated over 4 weeks up to a dose of 8 mg per day or the highest tolerated dose and treated for an additional 13 weeks on the last dose level achieved at the end of the titration period. The total treatment period was 17 weeks. Study drug was given once per day. The primary endpoint was the percent change from baseline in primary generalized tonic-clonic seizure frequency per 28 days during the treatment period as compared to the baseline period.  A statistically significant decrease in seizure rate was observed with Fycompa compared to placebo.

The use of Fycompa for the treatment of partial-onset seizures in adolescents and children 4 to <12 years with epilepsy is supported by efficacy extrapolated from three Phase 3 adequate and well-controlled studies of Fycompa in adult patients with partial-onset seizures. Safety was evaluated in two studies in pediatric patients 4 to <12 years of age with epilepsy, a total of 225 patients received Fycompa, with 110 patients exposed for at least 6 months, and 21 patients for at least 1 year. Adverse reactions in pediatric patients 4 to <12 years of age were similar to those seen in patients 12 years of age and older.

Side Effects

Adverse events associated with the use of Fycompa may include, but are not limited to, the following:

  • dizziness
  • somnolence
  • fatigue
  • irritability
  • falls
  • nausea
  • weight gain
  • vertigo
  • ataxia
  • gait disturbance
  • balance disorder

The Fycompa drug label comes with the following Black Box Warning: Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking Fycompa. Monitor patients for these reactions as well as for changes in mood, behavior, or personality that are not typical for the patient, particularly during the titration period and at higher doses. Fycompa should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening.

Mechanism of Action

Fycompa (perampanel) is a non-competitive antagonist of the ionotropic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal over excitation.

Literature References

Krauss GL, Perucca E, Ben-Menachem E, Kwan P, Shih JJ, Squillacote D, Yang H, Gee M, Zhu J, Laurenza A Perampanel, a selective, noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: Interim results from phase III, extension study 307. Epilepsia 2012 Aug 20. doi: 10.1111/j.1528-1167.2012.03648.x

French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D, Laurenza A Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia 2012 Aug 20. doi: 10.1111/j.1528-1167.2012.03638.x

French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, Kumar D, Rogawski MA Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304 Neurology 2012 Aug 7;79(6):589-96. doi: 10.1212/WNL.0b013e3182635735

Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, Yang H, Squillacote D, Edwards HB, Zhu J, Laurenza A Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 2012 May 1;78(18):1408-15

Additional Information

For additional information regarding Fycompa or partial seizures, please visit https://www.fycompa.com/