Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions
and/or revisions underlined:
Partial-Onset Seizures
Adult
and Adolescent Patients (12 years of age and older)
Table
2. Adverse Reactions in Pooled
Placebo-Controlled Trials in Adult and Adolescent Patients with Partial- Onset Seizures
(Studies 1, 2, and 3) (Reactions ? 2% of Patients in Highest FYCOMPA Dose (12 mg) Group and More Frequent
than Placebo)
Addition
of the following:
Pediatric
Patients (4 to <12 years of age)
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.
Additions
and/or revisions underlined:
… Similar increases in weight were also
observed in adult and adolescent patients …
8
Use in Specific Populations
8.4 Pediatric Use
Additions
and/or revisions underlined:
Safety and effectiveness of
FYCOMP A for the treatment of partial-onset seizures have been established
in pediatric patients 4 years of age and older.
The safety and effectiveness of FYCOMP A in
patients 12 years of age and older was established by three randomized
double-blind, placebo-controlled, multicenter studies, which included 72 pediatric
patients between 12 and 16 years of age exposed to FYCOMPA. Use of FYCOMPA for the
treatment of partial-onset seizures in pediatric patients 4 years to less than
12 years of age is supported by evidence from adequate and well-controlled
studies of FYCOMP A in patients 12 years of age and older with partial onset
seizures, pharmacokinetic data from adult and pediatric patients, and safety
data in 225 pediatric patients 4 years to less than 12 years of age
treated with FYCOMPA.
… The safety and effectiveness of
FYCOMPA for the treatment of partial-onset seizures in pediatric patients
less than 4 years of age or for the treatment of primary generalized
tonic-clonic seizures in pediatric patients less than 12 years of age have
not been established.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
(new subsection added)
Drug Reaction with Eosinophilia and Systemic
Symptoms (DRESS), also known as Multiorgan hypersensitivity, has been reported
in patients taking antiepileptic drugs, including FYCOMPA. DRESS may be fatal
or life-threatening. DRESS typically, although not exclusively, presents with
fever, rash, lymphadenopathy, and/or facial swelling, in association with other
organ system involvement, such as hepatitis, nephritis, hematological
abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.
Eosinophilia is often present. Because this disorder is variable in its
expression, other organ systems not noted here may be involved. It is important
to note that early manifestations of hypersensitivity, such as fever or
lymphadenopathy, may be present even though rash is not evident. If such signs
or symptoms are present, the patient should be evaluated immediately. FYCOMPA
should be discontinued if an alternative etiology for the signs or symptoms
cannot be established.
6
Adverse Reactions
(additions underlined)
The following serious adverse reactions are
described below and elsewhere in the labeling:
Serious Psychiatric
and Behavioral Reactions
Suicidal Behavior
and Ideation
Neurologic Effects
Falls
Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
7
Drug Interactions
7.2 Moderate and Strong CYP3A4 Inducers
(additions underlined)
The concomitant use of known moderate and strong
CYP3A4 inducers including carbamazepine, phenytoin, or oxcarbazepine with
FYCOMPA decreased the plasma levels of perampanel by approximately 50-67%. The
starting doses for FYCOMPA should be increased in the presence of moderate
or strong CYP3A4 inducers.
When these moderate or strong CYP3A4 inducers
are introduced or withdrawn from a patient’s treatment regimen, the patient
should be closely monitored for clinical response and tolerability. Dose
adjustment of FYCOMPA may be necessary.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(additions
underlined)
…
FYCOMPA is a
controlled substance (CIII) because it can be abused or lead to drug
dependence. Keep your FYCOMPA in a safe place to protect it from theft. Never
give your FYCOMPA to anyone else because it may harm them. Selling or giving
away this medicine is against the law.
It
is not known if FYCOMPA is safe and effective in children under 12 years of
age.
...
What are the possible side effects of
FYCOMPA?
See “What is the
most important information I should know about FYCOMPA?” FYCOMPA may cause
other serious side effects, including:
Dizziness, vertigo (sense of spinning),
and problems walking normally. You
may have problems walking normally if you are unsteady because you feel dizzy.
These symptoms can increase when your dose of FYCOMPA is increased. Your risk
of feeling dizzy and having problems walking normally may be higher if you are
elderly.
Sleepiness and tiredness. See “What should I avoid while taking FYCOMPA?”
Increased risk of falls. Taking FYCOMPA can increase your chance of falling.
These falls can cause serious injuries. Your risk of falling may be higher if
you are elderly.
A serious allergic reaction that may
affect your skin or other parts of your body such as your liver, kidneys,
heart, or blood cells. This
allergic reaction can be life-threatening and can cause death. Call your healthcare provider right away if
you have:
a skin rash, hives
fever or swollen glands that do not go away
swelling of your face
shortness of breath, swelling of the legs, yellowing
of the skin or whites of the eyes, or dark urine.
…
PATIENT COUNSELING INFORMATION
(additions underlined)
…
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.
…
DRESS/Multi-organ
Hypersensitivity
Instruct
patients that a fever associated with signs of other organ system involvement
(e.g., rash, lymphadenopathy, hepatic dysfunction) may be drug-related and
should be reported to their healthcare provider immediately.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Psychiatric and Behavioral Reactions
…In the postmarketing setting, there have been
reports of psychosis (acute psychosis, hallucinations, delusions, paranoia) and
delirium (delirium, confusional state, disorientation, memory impairment) in
patients treated with FYCOMPA. (addition underlined)
6
Adverse Reactions
6.2 Postmarketing Experience
Psychiatric: Acute
psychosis, hallucinations, delusions, paranoia, delirium, confusional state,
disorientation, memory impairment (additional category underlined)
8
Use in Specific Populations
8.1 Pregnancy
(PLLR Conversion)
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors
pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as
FYCOMPA, during pregnancy. Encourage women who are taking FYCOMPA during
pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy
Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org.
Risk Summary
There are no adequate data on the developmental risk associated
with use in pregnant women. In
animal studies, perampanel induced developmental toxicity in pregnant rat and
rabbit at clinically relevant doses [see
Data]. In the U.S. general population the estimated background risk of
major birth defects and miscarriage in clinically recognized pregnancies is
2-4% and 15-20%, respectively. The background risk of major birth defects and
miscarriage for the indicated population is unknown.
Data
Animal Data
Oral administration of perampanel (1, 3, or 10
mg/kg/day) to pregnant rats throughout organogenesis resulted in an increase in
visceral abnormalities (diverticulum of the intestine) at all doses tested;
maternal toxicity was observed at the mid and high doses. In a dose-ranging
study at higher oral doses (10, 30, or 60 mg/kg/day), embryo lethality and
reduced fetal body weight were observed at the mid and high doses tested. The
lowest dose tested (1 mg/kg/day) is similar to a human dose of 8 mg/day based
on body surface area (mg/m2).
Upon oral administration of perampanel (1, 3, or 10 mg/kg/day)
to pregnant rabbits throughout organogenesis, embryo lethality and maternal toxicity were observed at
the mid and high doses tested; the no-effect dose for embryo-fetal
developmental toxicity in rabbit (1 mg/kg/day) is approximately 2 times a human
dose of 8 mg/day based on body surface area (mg/m2).
Oral administration of perampanel (1, 3, or 10
mg/kg/day) to rats throughout gestation and lactation resulted in fetal and pup
deaths at the mid and high doses (associated with maternal toxicity) and
delayed sexual maturation in males and females at the highest dose tested. No
effects were observed on measures of neurobehavioral or reproductive function
in the offspring. The no-effect dose for pre- and postnatal developmental
toxicity in rat (1 mg/kg/day) is similar to a human dose of 8 mg/day based on
body surface area (mg/m2).
8.2 Lactation
(PLLR Conversion)
Risk Summary
There are no data on the presence of perampanel
in human milk, the effects on the breastfed child, or the effects of the drug
on milk production. Perampanel
and/or its metabolites are present in rat milk, and are detected at
concentrations higher than that in maternal plasma.
The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for
FYCOMPA and any potential adverse effects on the breastfed child from FYCOMPA
or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
(PLLR Conversion)
Contraception (Additional subsection)
Use of FYCOMPA may reduce the efficacy of hormonal
contraceptives containing levonorgestrel. Advise women taking FYCOMPA who are
using a levonorgestrel-containing contraceptive to use an additional
non-hormonal form of contraception while using FYCOMPA and for a month after
discontinuation.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
Use an additional non-hormonal form of
contraception (like condoms or a diaphragm and spermicide) while using FYCOMPA
and for 1 month after you have stopped taking FYCOMPA. What is the most
important information I should know about FYCOMPA?
1. FYCOMPA may cause mental (psychiatric)
problems, including:
What is FYCOMPA?
FYCOMPA is a prescription medicine that is used
with other medicines to treat …
Before
taking FYCOMPA?
tell
your healthcare provider about all of your medical conditions, including
if you:
Especially
tell your healthcare provider if you take:
How
should I take FYCOMPA?
See the complete
Instructions for Use below for information on how to use the dosing syringes
and measure your dose of FYCOMPA Oral Suspension.
If you take FYCOMPA Oral
Suspension, shake the bottle well before you take each dose.
Measure your dose of
FYCOMPA Oral Suspension using the bottle adapter and dosing syringes provided. Do
not use a household teaspoon.
What
should I avoid while taking FYCOMPA?
Do not drink alcohol or take other medicines …make your sleepiness or dizziness worse… FYCOMPA
when taken with alcohol may also make your mood worse, increase anger,
confusion, and depression.
What
are the possible side effects of FYCOMPA?
The most common side effects of FYCOMPA include
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling
(Medication Guide and Instructions
for
Use).
Administration
of Oral Suspension Additional subsection)
Advise patients who are prescribed the oral
suspension to shake the bottle well before every administration and to use the
adaptor and oral dosing syringe provided. Advise patients that a household
teaspoon or tablespoon is not an adequate measuring device. Instruct patients to discard any unused FYCOMPA oral
suspension remaining 90 days after first opening the bottle.
Serious
Psychiatric and Behavioral Reactions
Counsel patients, families, and caregivers of
patients of the need to monitor for the emergence of anger, aggression,
hostility, hallucinations, delusions, confusion, unusual changes in mood, personality, or
behavior, and other behavioral symptoms. (Additions
underlined)
Contraceptives
Counsel females of
reproductive potential that
FYCOMPA may decrease
efficacy of contraceptives containing levonorgestrel, and advise them
to use an additional non-hormonal form of contraception while using FYCOMPA and
for a month after discontinuation. (Additions
underlined)
Pregnancy
Registry
Advise women who are exposed to FYCOMPA during
pregnancy that there is a pregnancy exposure registry
that monitors pregnancy outcomes. Encourage these patients to enroll in the
NAAED Pregnancy Registry. (Additions
underlined)
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