New Drug Review: Eisai Inc's Fycompa

Fycompa (perapanel) tablets are approved for the treatment of partial-onset seizures in patients 12 years and older.

The FDA approved Eisai Inc's Fycompa (perampanel) tablets as an adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients 12 years and older with epilepsy.¹ Fycompa, a noncompetitive alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is the first in its class to receive FDA approval for seizure control.

Epilepsy affects approximately 2.2 million Americans, and about 60% of those affected have partial seizures. Approximately 25% to 35% of patients are unable to adequately control their seizures with treatments.²

The approval includes a boxed warning regarding the risk of serious and sometimes life-threatening neuropsychiatric events, such as irritability, aggression, anger, anxiety, paranoia, euphoric mood, agitation, and mental status changes.³ The FDA has recommended that Fycompa be classified by the US Drug Enforcement Administration as a scheduled drug.²

Pharmacology and Pharmacokinetics

Fycompa is a noncompetitive AMPA glutamate receptor antagonist on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is associated with several neurologic disorders caused by neuronal overexcitation. The exact mechanism by which Fycompa exerts its effect has not been fully determined.

The half-life of Fycompa is approximately 105 hours. Steady state is obtained in 2 to 3 weeks. Food does not affect the extent of absorption, but it does slow the rate of absorption. Clearance of Fycompa is about 17% slower in women than in men; however, no dose adjustment is necessary. Neither race nor age affect the pharmacokinetics of Fycompa.¹

Dosage and Administration

In patients who are not concomitantly using enzyme-inducing antiepileptic drugs (AEDs), Fycompa should be initiated as 2 mg orally at bedtime. In patients who are concomitantly using AEDs (such as phenytoin, carbamazepine, and oxcarbazepine), Fycompa should be initiated as 4 mg orally at bedtime. The dose may be increased by 2 mg increments no more frequently than every week to a dose of 4 to 12 mg once daily at bedtime. In elderly patients, dose increases should not be more frequent than every 2 weeks.

Patients with mild hepatic impairment should not receive more than 6 mg once daily at bedtime. Patients with moderate hepatic impairment should not receive more than 4 mg once daily at bedtime. Patients with severe hepatic or renal impairment should not use Fycompa.¹

Clinical Trials

Fycompa was evaluated in 3 multicentered, randomized, double-blind, placebo-controlled, dose-escalation, parallel group trials. Patients 12 years and older with partial-onset seizures received either Fycompa or placebo as an adjunctive treatment. All 3 studies found a statistically significant reduction in seizure rate with Fycompa doses of 4 to 12 mg per day. Although dose response was noted at 4 to 8 mg per day, there was minimal reduction in seizure frequency with the 12-mg per day dose.^1,2

Contraindications, Warnings, and Precautions

Serious or life-threatening psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats, have been reported in patients using Fycompa. These reactions occurred in patients both with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression. Patients should be closely monitored for changes in mood, behavior, or personality and a health care provider should be contacted immediately if changes occur.

There are no contraindications to treatment with Fycompa.

Patients using Fycompa should be monitored for suicidal thoughts or behavior. Dose-related increases in dizziness, gait disturbance, somnolence, and fatigue have been reported during use with Fycompa. There is an increased risk of falls during treatment. Withdrawal of Fycompa may result in increased seizure activity.

Fycompa 12 mg daily may decrease the effectiveness of contraceptives that contain levonorgestrel. Cytochrome P450 (CYP) inducers, such as carba-mazepine, oxcarbazepine, and phenytoin, increase the clearance of Fycompa and decrease its effectiveness. Phenobarbital and primidone may also decrease Fycompa concentrations. Avoid concomitant use with strong CYP3A4 inducers other than AEDs, such as rifampin and St. John's wort.

Fycompa is Pregnancy Category C. Use caution in patients who are breast-feeding. The most common adverse reactions (.4% and .1% higher than placebo) were dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, gait disturbance, and balance disorder.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, AZ.

References

• Fycompa complete prescribing information. http://us.eisai.com/package_inserts/FycompaPI.pdf. Accessed December 2012.
• Eisai announces FDA approval of Fycompa (perampanel) for the adjunctive treatment of partial-onset seizures in patients with epilepsy age 12 and older. http://us.eisai.com/view_press_release.asp?ID=147&press=382. Accessed December 2012.
• FDA approves Fycompa to treat seizures. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325038.htm. Accessed December 2012.