Drug Interaction:
Contraceptives: 12 mg once daily dose may decrease the effectiveness
of hormonal contraceptives containing levonorgestrel
Cytochrome P450 Inducers: Carbamazepine, oxcarbazepine and phenytoin
increase clearance of perampanel and decrease perampanel
plasma concentrations and decrease FYCOMPA¡¦s effectiveness.
There is insufficient information to describe dose adjustments that
can fully correct for this.
Phenobarbital and primidone may also decrease perampanel concentrations
. When these enzyme-inducing AEDs are introduced or withdrawn,
patients should be closely monitored. Dose adjustment of
FYCOMPA may be necessary
Strong CYP3A Inducers Other than AEDs: (e.g., rifampin, St. John¡¦s wort)
should be avoided
Indication:
FYCOMPA (perampanel) tablets, for oral use
Initial U.S. Approval: 2012
WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
See full prescribing information for complete boxed 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
Drug Name- Fycompa
Active Ingredient - Perampanel
To treat partial onset seizures in patients with epilepsy
ages 12 years and older
Indication-
Partial onset seizures in patients with epilepsy ages 12 years and older
Approved by FDA on 22-10--2012 (Ref- FDA approved List- 2012)
Adverse Reaction:
Most common adverse reactions (.4% and .1% higher than placebo) include
dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo,
ataxia, gait disturbance, and balance disorder.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behavior
Neurologic Effects: Monitor for dizziness, gait disturbance, somnolence,
and fatigue Patients should use caution when driving or operating machinery
Falls: Monitor for falls and injuries
Withdrawal of Antiepileptic Drugs: In patients with epilepsy, there may be an
increase in seizure frequency
Dosages/ Overdosage Etc:
Indication-
Partial onset seizures in patients with epilepsy ages 12 years and older
INDICATIONS AND USAGE
FYCOMPA, a non-competitive AMPA glutamate receptor antagonist,
is indicated as adjunctive therapy for the treatment of partial-onset
seizures with or without secondarily generalized seizures in patients
with epilepsy aged 12 years and older
DOSAGE AND ADMINISTRATION
Starting dose is 2 mg once daily at bedtime in patients not on
enzyme-inducing anti-epileptic drugs and 4 mg in patients on
enzyme-inducing AEDs
May increase based on clinical response and tolerability by a
maximum of 2 mg once daily at bedtime in weekly increments
to a dose of 4 mg to 12 mg once daily at bedtime.
Dose increases should occur no more frequently than at weekly
intervals
Maximum recommended daily dose is 12 mg once daily at bedtime
Elderly patients: Maximum frequency for dosage increases is every
two weeks.
Patients with Mild and Moderate Hepatic Impairment:
Maximum recommended daily dose is 6 mg and 4 mg once daily
at bedtime for patients with mild and moderate hepatic impairment, r
espectively.
Maximum frequency for dosage increases is every two weeks
„h Patients with Severe Hepatic Impairment: Not recommended (2.2)
Patients with Severe Renal Impairment or on hemodialysis:
Not recommended
DOSAGE FORMS AND STRENGTHS
Tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Inform patients of the availability of a Medication Guide, and instruct them to read
the Medication Guide prior to taking FYCOMPA.
Instruct patients to take FYCOMPA only as prescribed.
1. Serious Psychiatric and Behavioral Reactions
Counsel patients, families and caregivers of patients of the need to monitor for
the emergence of anger, aggression, hostility, unusual changes in mood,
personality, or behavior, and other behavioral symptoms.
Advise them to report any such symptoms immediately to their health care providers.
2. Suicidal Thinking and Behavior
Counsel patients, their caregivers, and families that AEDs, including FYCOMPA,
may increase the risk of suicidal thinking and behavior and advise them of the
need to be alert for the emergence or worsening of symptoms of depression,
any unusual changes in mood or behavior, or the emergence of suicidal thoughts,
behavior, or thoughts about self-harm. Instruct patients, caregivers and
families to report behaviors of concern immediately to healthcare providers.
3. Neurologic Effects:
Dizziness, Gait Disturbance, Somnolence, and Fatigue Counsel patients that
FYCOMPA may cause dizziness, gait disturbance, somnolence, and fatigue.
Advise patients taking FYCOMPA not to drive, operate complex machinery,
or engage in other hazardous activities until they have become accustomed
to any such effects associated with FYCOMPA.
4. Falls
Counsel patients that FYCOMPA may cause falls and injuries.
5. Withdrawal of Antiepileptic Drugs
Counsel patients that abrupt discontinuation of FYCOMPA may increase seizure
frequency.
6. Contraceptives.
Counsel patients that FYCOMPA may decrease efficacy of contraceptives
containing levonorgestrel.
7. Alcohol and Other CNS Depressants
Counsel patients that FYCOMPA may enhance the impairment effects of alcohol.
These effects may also be seen if FYCOMPA is taken with other CNS depressants.
8. Missed Doses
Counsel patients that if they miss a dose, they should resume dosing the following
day at their prescribed daily dose. Instruct patients to contact their physician
if more than one day of dosing is missed.
9. Controlled Substance
Counsel patients that FYCOMPA is a controlled substance that can be misuse
and abused.
10. Pregnancy Registry
To provide information regarding the effects of in utero exposure to FYCOMPA,
recommend pregnant patients treated with FYCOMPA to enroll in the NAAED
Pregnancy Registry. This can be done by calling the toll free numbe
1-888-233-2334, and must be done by patients themselves.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Perampanel is a non-competitive antagonist of the ionotropic
á-amino-3-hydroxy-5-methyl-4isoxazolepropionic 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.
2. Pharmacokinetics
Pharmacokinetics of perampanel are similar in healthy subjects and patients with
partial-onset seizures. The half-life of perampanel is about 105 hours, so that
steady state is reached in about 2-3 weeks. AUC of perampanel increased
in a dose-proportional manner after single-dose administration of 0.2–12 mg
and after multiple-dose administration of 1-12 mg once daily.
Absorption Perampanel is rapidly and completely absorbed after oral dose.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women
. In animal studies, perampanel induced developmental toxicity in pregnant
rat and rabbit at clinically relevant doses.
FYCOMPA should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Nursing Mothers
Perampanel and/or its metabolites are excreted in rat milk, and are detected
at concentrations higher than that in maternal plasma. It is not known whether
this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercise
when FYCOMPA is administered to a nursing woman.
3.Pediatric Use
The safety and efficacy of FYCOMPA for the adjunctive therapy of
partial-onset seizures was established by three randomized double blind,
placebo-controlled, multicenter studies which included 72 pediatric patients
between 12 and 16 years old exposed to perampanel.
The safety and effectiveness of FYCOMPA in pediatric patients <12 years old have
not been established
4. Geriatric Use
Clinical studies of FYCOMPA did not include sufficient numbers of patients aged
65 and over to determine the safety and efficacy of FYCOMPA in the elderly
population. Because of increased likelihood for adverse reactions in the
elderly dosing titration should proceed slowly in patients aged 65 years
and older
