Perampanel

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using perampanel and call your doctor at once if you have a side effect such as:

• changes in mood, behavior, or personality;
• anger, aggression, anxiety, trouble sleeping, feeling hostile or irritable;
• talking more than usual;
• unusual thoughts, paranoid behavior, panic attacks;
• thoughts about suicide, or thoughts about hurting someone else;
• trouble walking, loss of balance or coordination;
• an accidental fall; or
• severe dizziness, spinning sensation, feeling like you might pass out.

Accidental falls may occur more often in elderly patients who take perampanel. Use caution to avoid falling or accidental injury while taking this medicine.

Common side effects may include:

• mild dizziness;
• drowsiness, tiredness;
• nausea;
• weight gain; or
• headache, joint pain, back pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Oral Administration

May take tablet or oral suspension with or without food

Tablet and oral suspension may be used interchangeably on a mg-per-mg basis

Oral suspension

• Shake well before measuring dose for each administrations
• Use provided adapter and graduated oral dosing syringe to accurately administer the oral suspension; household teaspoons or tablespoons are not an adequate measuring device
• The adapter, which is supplied in the product carton, should be inserted firmly into the neck of the bottle before use and remain in place for the duration of the usage of the bottle
• The dosing syringe should be inserted into the adapter and the dose withdrawn from the inverted bottle
• The cap should be replaced after each use; the cap fits properly when the adapter is in place
• Discard any unused oral suspension remaing 90 days after first opening the bottle

Storage

Tablet

• Store at room temperature: 68 - 77°F (20- 25°C); excursions permitted to 59-86°F (15-30°C)

Oral Suspension

• Do not store above 86°F (30°C). Do not freeze. Use within 90 days after the first opening of the bottle.

Perampanel may cause serious side effects. See "Drug Precautions" section.

The most common side effects include:

• dizziness
• sleepiness
• tiredness
• irritability
• falls
• nausea
• problems with muscle coordination
• problems walking normally
• vertigo (sense of spinning)
• weight gain

Tell your healthcare provider about any side effect that bothers you or does not go away.

These are not all of the possible side effects of perampanel. For more information ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Perampanel may cause serious side effects including:

1. Perampanel may cause mental (psychiatric) problems. Tell your healthcare provider right away if you have any new or worsening mental problems including:
   • new or worse aggressive behavior (including homicidal behavior), hostility, anger, anxiety, or irritability
   • being suspicious or distrustful (believing things that are not true)
   • other unusual or extreme changes in behavior or mood
2. Like other antiepileptic drugs, perampanel may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you. Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
   • thoughts about suicide or dying
   • attempt to commit suicide
   • new or worse depression
   • new or worse anxiety
   • feeling agitated or restless
   • panic attacks
   • trouble sleeping (insomnia)
   • new or worse irritability
   • acting aggressive, being angry, or violent
   • acting on dangerous impulses
   • an extreme increase in activity and talking (mania)
   • other unusual changes in behavior or mood

Watch for early symptoms of suicidal thoughts and actions:

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

• Keep all follow-up visits with your healthcare provider as scheduled.

Perampanel 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 perampanel is increased. Your risk of feeling dizzy and having problems walking normally may be higher if you are elderly.
• Sleepiness and tiredness.
• Increased risk of falls. Taking perampanel can increase your chance of falling. These falls can cause serious injuries. Your risk of falling may be higher if you are elderly.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop perampanel without first talking with a healthcare provider. Stopping perampanel suddenly can cause serious problems. Stopping perampanel suddenly can cause you to have seizures more often.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of perampanel there are no specific foods that you must exclude from your diet when receiving this medication.
 

Usual Adult Dose for Seizures:

Patients NOT Receiving Concomitant Enzyme-Inducing Antiepileptic Drugs (AEDs):
-Partial-Onset Seizures:
Initial Dose: 2 mg orally once a day at bedtime.
Maintenance Dose: 8 to 12 mg/day; some patients may respond to 4 mg/day.
-Primary Generalized Tonic-Clonic Seizures:
Initial Dose: 2 mg orally once a day at bedtime.
Maintenance Dose: 8 mg/day; if needed and tolerated, may increase up to 12 mg/day for patients requiring further seizure reduction.

Patients Receiving Concomitant Enzyme-Inducing AEDs:
Partial-Onset AND Primary Generalized Tonic-Clonic Seizures:
-Initial Dose: 4 mg orally once a day at bedtime.
-Maintenance Dose: Has not been established.
-Maximum Dose: Has not been established; the highest dose studied was 12 mg once a day.

Comments: May increase dosage by increments of 2 mg/day no more frequently than at weekly intervals.

Use: Adjunctive therapy in patients with epilepsy for treatment of partial-onset seizures with or without secondarily generalized seizures, and for primary generalized tonic-clonic seizures.

Usual Geriatric Dose for Seizures:

Increase dosage no more than every 2 weeks during titration.

Usual Pediatric Dose for Seizures:

Age 12 Years and Older:

Patients NOT Receiving Concomitant Enzyme-Inducing Antiepileptic Drugs (AEDs):
-Partial-Onset Seizures:
Initial Dose: 2 mg orally once a day at bedtime.
Maintenance Dose: 8 to 12 mg/day; some patients may respond to 4 mg/day.
-Primary Generalized Tonic-Clonic Seizures:
Initial Dose: 2 mg orally once a day at bedtime.
Maintenance Dose: 8 mg/day; if needed and tolerated, may increase up to 12 mg/day for patients requiring further seizure reduction.

Patients Receiving Concomitant Enzyme-Inducing AEDs:
Partial-Onset AND Primary Generalized Tonic-Clonic Seizures:
-Initial Dose: 4 mg orally once a day at bedtime.
-Maintenance Dose: Has not been established.
-Maximum Dose: Has not been established; the highest dose studied was 12 mg once a day.

Comments: May increase dosage by increments of 2 mg/day no more frequently than at weekly intervals.

Use: Adjunctive therapy in patients with epilepsy for treatment of partial-onset seizures with or without secondarily generalized seizures, and for primary generalized tonic-clonic seizures.

Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking 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.

Storage

Oral

25°C (may be exposed to 15–30°C).1

• Exact mechanism of anticonvulsant action not fully elucidated; however, the drug inhibits AMPA-type glutamate receptors, a class of ionotropic glutamate receptors that mediate fast excitatory neurotransmission and play a role in the generation and spread of epileptic seizures.1 14 15 16 22 23

• Selectively and noncompetitively inhibits AMPA glutamate receptors on postsynaptic neurons, thereby reducing excessive glutamatergic activity and neuronal excitation.1 5 16

• Highly selective for AMPA glutamate receptors; little or no inhibitory effect on N-methyl-d-aspartate (NMDA) or kainate glutamate receptors.14 22

• Demonstrates a broad spectrum of anticonvulsant activity in various animal models.16 19

There are no contraindications listed in manufacturer's US labeling.

Canadian labeling: Hypersensitivity to perampanel or any component of the formulation.

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 perampanel. These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression.

Advise patients and caregivers to contact a health care provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking perampanel or after discontinuing perampanel. Closely monitor patients, particularly during the titration period and at higher doses. Reduce perampanel if these symptoms occur, and discontinue the drug immediately if symptoms are severe or are worsening.

Seizure frequency/duration; suicidality (eg, suicidal thoughts, depression, behavioral changes) during therapy and for at least 1 month after discontinuation; weight

Applies to perampanel: oral suspension, oral tablet

General

When comparing the 8 mg and 12 mg once a day doses, the 12 mg dose resulted in somewhat greater reductions in seizure rates but with a substantial increase in adverse reactions.[Ref]

Nervous system

Very common (10% or more): Dizziness/vertigo (47%), somnolence (18%), gait disturbance (13%), headache (13%), irritability (12%)
Common (1% to 10%): Ataxia, dysarthria, gait disturbance, balance disorder, hypoesthesia, abnormal coordination, memory impairment, paresthesia[Ref]

Psychiatric

Very common (10% or more): Hostility- and aggression-related reactions (20%), irritability (11%)
Common (1% to 10%): Anxiety, anger, hypersomnia, euphoric mood, disorientation/confusional state, altered mood
Uncommon (0.1% to 1%): Homicidal ideation and/or threat, suicidal ideation, suicide attempt
Frequency not reported: Belligerence, affect lability, agitation, physical assault, paranoia, changed mental status, delusions
Postmarketing reports: Acute psychosis, hallucinations, delirium[Ref]

Other

Very common (10% or more): Fatigue/asthenia/lethargy (15%), falls (10%), limb injury
Common (1% to 10%): Head injury, peripheral edema[Ref]

Dermatologic

Common (1% to 10%): Contusion, skin laceration, rash
Postmarketing reports: Drug reaction with eosinophilia and systemic symptoms (DRESS)[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, vomiting, constipation, abdominal pain[Ref]

Metabolic

Common (1% to 10%): Weight gain, hyponatremia, decreased appetite, increased appetite
Frequency not reported: Increased triglycerides[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, myalgia, pain in extremity, arthralgia, musculoskeletal pain, ligament sprain
Frequency not reported: Bone fractures[Ref]

Ocular

Common (1% to 10%): Blurred vision, diplopia[Ref]

Respiratory

Common (1% to 10%): Cough, upper respiratory tract infection, oropharyngeal pain[Ref]

Some side effects of perampanel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Increase dosage no more than every 2 weeks during titration.