FDA Uses Extrapolation to Expand FYCOMPA® (Perampanel) Indication to Include Monotherapy Treatment of Partial-Onset Seizures (POS) in Patients 12 Years of Age and Older 

On July 26, 2017, the U.S. Food and Drug Administration (FDA) approved FYCOMPA (perampanel) for monotherapy use for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older.  Support for the use of perampanel as monotherapy for the treatment of POS is based on extrapolation of pharmacokinetic (PK) information deemed adequate to demonstrate that the proposed dosages of a drug, when used as monotherapy, should result in exposures that are similar to those demonstrated to be safe and effective when the drug is used as adjunctive therapy for the treatment of POS, taking into consideration possible drug-drug interactions (inhibition or induction) that may alter the metabolism of the drug. This extrapolation relied on population PK analyses (healthy subjects from 19 Phase 1 studies and pooled data from three POS pivotal Phase 3 studies) that were submitted to the FDA with the original NDA for adjunctive therapy of POS. 

The approved indications approved recommended dosages for FYCOMPA are
• For the treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older. 
The approved recommended starting dosage of FYCOMPA is 2 mg once daily taken orally at bedtime.  Increase dosage by 2 mg increments once daily based on individual clinical response and tolerability, no more frequently than at weekly intervals.  Recommended maintenance dose range in monotherapy or adjunctive therapy is 8 to 12 mg once daily although some patients respond to a dose of 4 mg daily.
• As adjunctive therapy for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. 
The approved recommended starting dosage of FYCOMPA is 2 mg once daily taken orally at bedtime.  Increase dosage by 2 mg increments once daily based on individual clinical response and tolerability, no more frequently than at weekly intervals.  Recommended maintenance dose is 8 mg once daily taken at bedtime.  Patients tolerating 8 mg once daily and who require further reduction of seizures may benefit from 12 mg once daily, if tolerated.

Dose modifications for concomitant use with moderate or strong CYP3A4 inducers, in patients with hepatic or renal impairment, and in elderly patients are described in the full prescribing information (link below).

Serious adverse reactions associated with use of FYCOMPA are serious psychiatric and behavioral reactions, suicidal behavior and ideation, neurologic effects, falls, and drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity.  The most common adverse reactions in patients with partial-onset seizures receiving FYCOMPA at doses of 8 mg or 12 mg included dizziness, somnolence, fatigue, irritability, falls, nausea, ataxia, balance disorder, gait disturbance, vertigo, and weight gain.  The most common adverse reactions in patients with primary generalized tonic-clonic seizures receiving FYCOMPA 8 mg were dizziness, fatigue, headache, somnolence, and irritability.
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Full prescribing information is available at https://go.usa.gov/xRprr. 

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products which are often available shortly following approval.