Fycompa

Perampanel comes as a tablet to take by mouth. It is usually taken once a day at bedtime. Take perampanel at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take perampanel exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor will probably start you on a low dose of perampanel and gradually increase your dose, not more than once every one to two weeks.

Perampanel may be habit forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.

Perampanel may help control your condition but does not cure it. Do not stop taking perampanel without talking to your doctor. If you suddenly stop taking perampanel, your seizures may become worse. Your doctor will probably decrease your dose gradually.

Perampanel may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness or a sense of spinning
• drowsiness
• constipation
• nausea
• vomiting
• weight gain
• irritability
• weakness
• problems with coordination
• muscle or joint pain
• blurred or double vision

Perampanel may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Fycompa is part of the drug class:

• Other antiepileptics

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Fycompa passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Fycompa. You and your healthcare provider should decide if you will take Fycompa or breastfeed. You should not do both.

The recommended starting dosage of Fycompa is 2 mg once daily taken orally at bedtime. Increase dosage by 2 mg per day increments no more frequently than every week. In elderly patients, dosage increases during titration are recommended no more frequently than every two weeks.

The recommended dose for treating primary generalized tonic-clonic seizures is 8 mg once daily at bedtime. 

The recommended maintenance dose range for treating partial-onset seizures is 8 mg to 12 mg once daily.

The dose will depend on how you tolerate the medication and how you respond to the medication. 

Your healthcare provider may recommend a different dose if you are taking certain other medications in combination with Fycompa. Dosage adjustments may also be recommended if you have liver or kidney disease.

The following serious adverse reactions are described below and elsewhere in the labeling:

• Serious Psychiatric and Behavioral Reactions [see WARNINGS AND PRECAUTIONS]
• Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
• Neurologic Effects [see WARNINGS AND PRECAUTIONS]
• Falls [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Partial-Onset Seizures

A total of 1,038 patients receiving FYCOMPA (2, 4, 8, or 12 mg once daily) constituted the safety population in the pooled analysis of the placebo-controlled trials (Studies 1, 2, and 3) in patients with partial-onset seizures. Approximately 51% of patients were female, and the mean age was 35 years.

In controlled clinical trials (Studies 1, 2, and 3), the rate of discontinuation as a result of an adverse reaction was 3%, 8%, and 19% in patients randomized to receive FYCOMPA at the recommended doses of 4 mg, 8 mg, and 12 mg per day, respectively, and 5% in patients randomized to receive placebo [see Clinical Studies]. The adverse reactions most commonly leading to discontinuation (≥1% in the 8 mg or 12 mg FYCOMPA group and greater than placebo) were dizziness, somnolence, vertigo, aggression, anger, ataxia, blurred vision, irritability, and dysarthria [see WARNINGS AND PRECAUTIONS].

Table 2 gives the incidence in the controlled clinical trials (Studies 1, 2, and 3) of the adverse reactions that occurred in ≥2% of patients with partial-onset seizures in the FYCOMPA 12 mg dose group and more frequent than placebo (in order of decreasing frequency for the 12 mg dose group).

The most common dose-related adverse reactions in patients receiving FYCOMPA at doses of 8 mg or 12 mg (≥4% and occurring at least 1% higher than the placebo group) included dizziness (36%), somnolence (16%), fatigue (10%), irritability (9%), falls (7%), nausea (7%), ataxia (5%), balance disorder (4%), gait disturbance (4%), vertigo (4%), and weight gain (4%). For almost every adverse reaction, rates were higher on 12 mg and more often led to dose reduction or discontinuation.

Table 2. Adverse Reactions in Pooled Placebo-Controlled Trials in 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)

Primary Generalized Tonic-Clonic Seizures

A total of 81 patients receiving FYCOMPA 8 mg once daily constituted the safety population in the placebo-controlled trial in patients with primary generalized tonic-clonic seizures (Study 4). Approximately 57% of patients were female, and the mean age was 27 years.

In the controlled primary generalized tonic-clonic seizure clinical trial (Study 4), the adverse reaction profile was similar to that noted for the controlled partial-onset seizure clinical trials (Studies 1, 2, and 3).

Table 3 gives the incidence of adverse reactions in patients receiving FYCOMPA 8 mg (≥4% and higher than in the placebo group) in Study 4. The most common adverse reactions in patients receiving FYCOMPA (≥10% and greater than placebo) were dizziness (32%), fatigue (15%), headache (12%), somnolence (11%), and irritability (11%).

The adverse reactions most commonly leading to discontinuation in patients receiving FYCOMPA 8 mg (≥2% and greater than placebo) were vomiting (2%) and dizziness (2%).

Table 3. Adverse Reactions in a Placebo-Controlled Trial in Patients with Primary Generalized Tonic-Clonic Seizures (Study 4) (Reactions ≥ 4% of Patients in FYCOMPA Group and More Frequent than Placebo)

Weight Gain

Weight gain has occurred with FYCOMPA.

In controlled partial-onset seizure clinical trials, FYCOMPA-treated adults gained an average of 1.1 kg (2.5 lbs) compared to an average of 0.3 kg (0.7 lbs) in placebo-treated adults with a median exposure of 19 weeks. The percentages of adults who gained at least 7% and 15% of their baseline body weight in FYCOMPA-treated patients were 9.1% and 0.9%, respectively, as compared to 4.5% and 0.2% of placebo-treated patients, respectively. Clinical monitoring of weight is recommended.

Similar increases in weight were also observed in adult and pediatric patients treated with FYCOMPA in the primary generalized tonic-clonic seizure clinical trial.

Elevated Triglycerides

Increases in triglycerides have occurred with FYCOMPA use.

Comparison Of Sex And Race

No significant sex differences were noted in the incidence of adverse reactions.

Although there were few non-Caucasian patients, no differences in the incidence of adverse reactions compared to Caucasian patients were observed.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of FYCOMPA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Dermatologic: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Psychiatric: Acute psychosis, hallucinations, delusions, paranoia, delirium, confusional state, disorientation, memory impairment [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Fycompa (Perampanel Tablets, for Oral Use)

You should not use perampanel if you are allergic to it.

To make sure perampanel is safe for you, tell your doctor if you have:

• liver disease;

• kidney disease;

• a history of depression or mental illness; or

• a history of alcoholism or drug addiction.

Some people taking perampanel have had serious psychotic effects such as anger, aggression, feeling hostile or irritable, and thoughts about hurting others. These effects may be more likely to occur when you first start taking perampanel, or whenever your dose is changed. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Do not start or stop taking seizure medication during pregnancy without your doctor's advice. Having a seizure during pregnancy could harm both mother and baby. Tell your doctor right away if you become pregnant.

Perampanel can make certain birth control pills less effective. Ask your doctor about using non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy while taking perampanel.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of perampanel on the baby.

It is not known whether perampanel passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

Perampanel is not approved for use by anyone younger than 12 years old.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor for instructions if you miss your perampanel dose for more than one day.

General

• When discontinuing anticonvulsant therapy, gradual withdrawal is recommended to minimize potential for increased seizure frequency.1 (See Discontinuance of Anticonvulsants under Cautions.)

• Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 (See Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer orally once daily at bedtime; may be given without regard to food.1 25 (See Absorption under Pharmacokinetics.)

Dosage

Initial dosage recommendations vary based on whether a CYP enzyme-inducing anticonvulsant agent (e.g., carbamazepine, oxcarbazepine, phenytoin) is administered concomitantly.1 6 Such CYP-inducing anticonvulsants can reduce plasma concentrations and thus efficacy of perampanel.1 6 8 (See Interactions.)

Monitor for adverse neuropsychiatric effects, particularly during initial titration period (or any other time dosage is increased) and when high dosages (e.g., 12 mg daily) are used.1 If neuropsychiatric manifestations occur, reduce dosage of perampanel or discontinue therapy depending on severity of the reaction.1 (See Serious Psychiatric and Behavioral Reactions under Cautions.)

Pediatric Patients

Children ≥12 years of age not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

Children ≥12 years of age concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

In principal efficacy studies, a dosage of 12 mg daily provided little additional benefit over 8 mg daily and was associated with an increased incidence of adverse effects (e.g., neuropsychiatric effects).2 3 6 15 In general, increase dosage to 12 mg daily only if tolerated and clinically indicated.2 3 6 15

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Children ≥12 years of age not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 8 mg once daily.1 Patients tolerating a dosage of 8 mg daily and who require further seizure control may benefit from a dosage increase to 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Children ≥12 years of age concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Adults

Patients not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

Patients concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to the recommended dosage range of 4–12 mg once daily; individualize dosage based on clinical response and tolerability.1

In principal efficacy studies, a dosage of 12 mg daily provided little additional benefit over 8 mg daily and was associated with an increased incidence of adverse effects (e.g., neuropsychiatric effects).2 3 6 15 In general, increase dosage to 12 mg daily only if tolerated and clinically indicated.2 3 6 15

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Patients not concomitantly receiving a CYP-inducing anticonvulsant: Initially, 2 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 8 mg once daily.1 Patients tolerating a dosage of 8 mg daily and who require further seizure control may benefit from a dosage increase to 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Patients concomitantly receiving a CYP-inducing anticonvulsant: Initially, 4 mg once daily.1 Increase dosage by increments of 2 mg daily no more frequently than once a week up to a dosage of 12 mg once daily.1 Adjust dosage based on clinical response and tolerability.1

Dosage adjustment may be necessary when CYP-inducing anticonvulsants are added to, or discontinued from, a patient's anticonvulsant regimen; closely monitor for clinical response and tolerability in such cases.1 (See Interactions.)

Prescribing Limits

Pediatric Patients

Pediatric patients ≥12 years of age: Maximum 12 mg once daily.1

Pediatric patients ≥12 years of age: Maximum 12 mg once daily.1

Adults

Maximum 12 mg once daily.1

Maximum 12 mg once daily.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: Initially, 2 mg once daily; may increase by increments of 2 mg daily no more frequently than once every 2 weeks up to a maximum of 6 mg once daily.1 Individualize dosage based on patient response and tolerability.1

Moderate hepatic impairment: Initially, 2 mg once daily; may increase by increments of 2 mg daily no more frequently than once every 2 weeks up to a maximum of 4 mg once daily.1 Individualize dosage based on patient response and tolerability.1

Severe hepatic impairment: Use not recommended.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild renal impairment: No dosage adjustment necessary.1

Moderate renal impairment: Consider a slower titration schedule based on patient response and tolerability; monitor closely.1

Severe renal impairment and patients undergoing hemodialysis: Use not recommended.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Patients ≥65 years of age: Titrate more slowly than usual, increasing dosage no more frequently than once every 2 weeks.1 (See Geriatric Use under Cautions.)

Gender or Race

Dosage adjustment not required.1

Contraindications

• None.1

Warnings/Precautions

Warnings

Serious, sometimes life-threatening, psychiatric and behavioral reactions reported.1 5 6 8 20

Adverse neuropsychiatric events include irritability, anger, agitation, anxiety, labile affect, belligerence, hostility, aggression, homicidal ideation and/or threats, and physical assaults.1 5 6 8 20 (See Boxed Warning.) Effects are dose related, generally occurring within the first 6 weeks of therapy.1 5

Some patients may experience worsening of their preexisting psychiatric condition.1

Suicidal ideation and suicide attempts also reported.2 4 6 8 26 (See Suicidality Risk under Cautions.)

Other neuropsychiatric effects such as disorientation/confusional state, delusion, paranoia, euphoric mood, and mental status changes also observed.1 6 (See Abuse Potential and Dependence under Cautions.)

Concomitant use of alcohol may substantially worsen mood and increase anger; avoid alcohol use during therapy.1 (See Specific Drugs under Interactions and also see Advice to Patients.)

Monitor for psychiatric and behavioral reactions as well as for unusual changes in mood, behavior, or personality during and for at least 1 month following discontinuance of therapy.1 (See Advice to Patients.) Monitoring is particularly important during the first few weeks of therapy (titration period), following dosage increases, and when higher dosages are used.1

If any such manifestations occur, reduce dosage; if symptoms are persistently severe or worsening, immediately and permanently discontinue perampanel and refer patient for psychiatric evaluation.1

Other Warnings and Precautions

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 10 11 12 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.1 10 11 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 10

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 Anxiety, agitation, hostility, hypomania, and mania may be precursors to emerging suicidality.10

Balance risk of suicidality with risk of untreated illness.1 10 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 12 If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 12 (See Advice to Patients.)

Risk of dose-related adverse neurologic effects (e.g., dizziness, vertigo, disturbances in gait or coordination, somnolence, fatigue); generally observed during dosage titration period.1 4 13 20 (See Advice to Patients.)

CNS-related events were among the most common adverse effects associated with perampanel in clinical studies;1 2 3 4 13 20 risk appears to be increased in geriatric patients and with concomitant use of alcohol and/or other CNS depressants.1 (See Geriatric Use under Cautions and also see Specific Drugs under Interactions.)

Falls (both with and without concurrent seizures), sometimes resulting in serious injuries (e.g., head injuries, bone fractures, lacerations), reported.1 3 Falls sometimes occurred in association with other CNS-related effects (e.g., gait disturbance, ataxia, dizziness, slurred speech).3 Risk appears to be greater in geriatric patients.1 8 (See Geriatric Use under Cautions.)

Abrupt withdrawal of anticonvulsants may increase seizure frequency in patients with seizure disorders.1 In general, gradual withdrawal is recommended whenever any anticonvulsant agent is discontinued.1 However, manufacturer states that insufficient data are available to make specific recommendations regarding withdrawing perampanel.1 Because of its prolonged half-life (approximately 105 hours), plasma concentrations are expected to decline gradually even after abrupt discontinuance.1 If discontinuance of perampanel is necessary because of adverse effects, may consider prompt withdrawal of the drug.1

Subject to control as a schedule III (C-III) drug.1 7 Abuse potential may result in moderate to low physical dependence or high psychological dependence.7

Potential to produce withdrawal symptoms not adequately evaluated to date.1 (See Discontinuance of Anticonvulsants under Cautions.)

Specific Populations

Category C.1

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .1

Distributed into milk in rats; not known whether distributed into human milk.1 Caution advised when used in nursing women.1

Safety and efficacy not established in children <12 years of age.1

In controlled studies in patients with partial-onset seizures, aggression observed more frequently in adolescents than in adults.1 (See Serious Psychiatric and Behavioral Reactions under Cautions.)

No evidence of an overall negative effect on cognitive function in a short-term controlled study in adolescent patients.1

Insufficient experience in patients ≥65 years of age to establish efficacy and safety in this population.1

Because of a greater likelihood of adverse effects (e.g., dizziness, gait disturbances, falls, somnolence, fatigue), titrate dosage gradually in patients ≥65 years of age.1 (See Geriatric Patients under Dosage and Administration.)

Systemic exposure and half-life of perampanel are increased in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment; dosage adjustments recommended.1 (See Hepatic Impairment under Dosage and Administration and also see Pharmacokinetics.)

Not studied in patients with severe hepatic impairment; use not recommended.1

Not specifically evaluated to date in patients with renal impairment, but population pharmacokinetic analyses indicate that clearance may be reduced.1 (See Elimination: Special Populations, under Pharmacokinetics.)

Use with close monitoring in patients with moderate renal impairment; consider more gradual dosage titration.1 (See Renal Impairment under Dosage and Administration.)

Not studied in patients with severe renal impairment and in those undergoing hemodialysis; use not recommended.1

Common Adverse Effects

Partial-onset seizures: Dizziness,1 2 3 4 somnolence,1 2 3 4 fatigue,1 3 4 irritability,1 2 3 falls,1 2 3 nausea,1 3 weight gain,1 3 vertigo,1 ataxia,1 2 gait disturbance,1 4 balance disorder.1

Primary generalized tonic-clonic seizures: Dizziness,1 fatigue,1 headache,1 somnolence,1 irritability.1

There is limited clinical experience with Fycompa overdose. The highest reported overdose (approximately 264 mg) was intentional. This patient experienced serious adverse reactions of altered mental status, agitation, and aggressive behavior and recovered without sequelae. In general, the adverse reactions associated with overdoses were similar to the reactions at therapeutic doses with dizziness reported most frequently. There were no reported sequelae.

There is no available specific antidote to the overdose reactions of Fycompa. In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with Fycompa. Due to its long half-life, the reactions caused by Fycompa could be prolonged.

Some people taking Fycompa have had serious psychotic effects, especially when starting this medicine or changing doses. Stay alert to changes in your mood or symptoms.

Call your doctor right away if you have any changes in mood or behavior changes, personality changes, thoughts about suicide, or thoughts about hurting others. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking Fycompa with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety or depression.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• birth control pills;

• rifampin;

• St. John's wort;

• other seizure medicine- carbamazepine, oxcarbazepine, phenytoin.

This list is not complete. Other drugs may interact with perampanel, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.