ADVERTISEMENT
ADVERTISEMENT

Perampanel is a first in class, noncompetitive antagonist of a particular glutamate receptor known as AMPA, which are found on postsynaptic neurons.

Glutamate is a primary neurotransmitter involved in excitation in the central nervous system and is implicated in a number of conditions, particularly epilepsy. Although, the precise way by which Perampanel exerts its effects in humans is not fully understood but it is believed to be through this mechanism.

Fycompa
Tablet
2mg perampanel

2 mg – orange color, '2' on one side, '275' on the other 

4mg perampanel

 4 mg – red color, '4' on one side, '277' on the other 

6mg perampanel

 6 mg - pink color, '6' on one side, '294' on the other 

8mg perampanel

 8 mg - purple color, labeled '8' on one side and '295' on the other 

10mg perampanel

 10 mg – green color, labeled '10' on one side and '296' on the other 

12mg perampanel

 12 mg – blue color, labeled '12' on one side and '297 on the other 

Used to Treat

  • Temporal Lobe Epilepsy
  • Complex Partial Seizures
  • Refractory Seizures
  • Secondarily Generalized Seizures
  • Simple Partial Seizures

Forms

Please see package insert.

How to Take and Store

Please see package insert for complete information.  The recommended starting dose of Fycompa in adults is 2 mg once daily at bedtime.  The dose can be increased by 2 mg per day increments no faster than every week.  For adullts over the age of 65 years, the dose should not be increased no faster than every 2 weeks.

How to take and store Perampanel?
  • The medicine can be taken once a day in the evening.
  • Fycompa, like most seizure medicines, is usually started slowly and increased each week (or more slowly) to the prescribed dose.
  • The medicine is usually started slower in older people. Dosages may also be different in people who are older or who have mild or moderate problems with kidney or liver function.
  • Store the medication at room temperature between 59 to 86°F or 15 to 30° C.
  • Keep Fycompa out of reach of children.
  • Do not give the medicine to anyone else.
What if I forget?
  • For Fycompa to work best, it should be taken the same way each day.
  • Avoid missing doses and don’t take more medicine than prescribed by your doctor or licensed provider.
  • Talk to your health care prescriber about what to do if you miss a dose, especially if you miss more than one dose.
How does Perampanel effect the brain?

Fycompa is the first drug from a new type of medicines approved by the FDA to treat seizures.

  • It is a noncompetitive antagonist of a glutamate receptor known as AMPA.
  • Glutamate is a key substance (called neurotransmitter) that acts to excite nerve cells in the brain or central nervous system. It’s thought to be important in many conditions, including epilepsy.
  • The exact way that Perampanel works in the brain to stop seizures is not fully understood, it’s thought to work by affecting or blocking these glutamate receptors in the brain.
How does the body digest Perampanel?

How Perampanel is digested and works in the body has been studied in healthy adults with partial seizures, as well as in other neurological and medical conditions.

  • Perampanel is easily absorbed after being swallowed.
  • When this medicine is taken with food, the peak concentration is slowed down. This means that it takes 2 hours longer for the drug to reach its’ peak amount in the blood stream when it is taken with or after food.
  • The drug has a half-life of over 4 days, which means it will take 2 to 3 weeks for the medicine to reach a steady state in the body once it has begun or the dose has been changed.
  • The drug is metabolized or broken down in the liver. The primary method of metabolism involves CYP3A, one of the cytochrome P450 enzymes that affects the way drugs are broken down in the liver.
  • This form of liver metabolism may affect how Fycompa interacts with other medications. These drug interactions need to be considered when choosing and monitoring the drug.
  • The drug has linear pharmacokinetics and there is a relationship between the dose taken and the concentration in the body over the dose range of 2-12 mg. per day.
How well does the Perampanel work?

Fycompa’s effectiveness was proven through three trials in which it was used as add-on treatment for partial seizures given on a once a day basis. These trials were randomized, double blind, and placebo-controlled. They were conducted at many centers in the U.S in both adults and adolescents with epilepsy.

  • Two studies compared doses of Fycompa at 8 and 12 mg per day with a placebo (a non-active pill). The third study compared doses of 2, 4, and 8 mg of Perampanel against placebo.
  • The responder rate was 29% for 4 mg a day; 35% for 8 mg a day; and 35% for 12 mg per day. No greater benefit was observed at 12 mg daily as compared to 8 mg daily.
    • This means that 29 to 35% of people had at least a 50% decrease in their seizures at doses of 4 mg to 12 mg per day. Eight to 12 mg per day worked a little better than the lower dose of 4 mg a day.
  • A clinically meaningful decrease in seizure frequency was observed as early as the second week on the medication, once patients reached a daily dose of 4 mg.
  • Studies of Fycompa in children are being done. The drug is not approved for use in children under age 12.
  • There have been three key double blind, placebo-controlled studies for adolescents between the age of 12 and 18. The results in these adolescents are similar to those seen in the adults studied.
What are the most common side effects of Perampanel?

The most common side effects reported include:

(Common means that the effects occurred in 4% or more of patients and were greater in people taking the Fycompa than in patients taking placebo.)

  • Dizziness
  • Sleepiness or tiredness
  • Irritability
  • Anxiety
  • Stomach upset or nausea
  • Problems walking - Imbalance or unsteadiness
  • Problems with muscle coordination
  • Falls
  • Vertigo or dizziness
  • Weight gain
  • Blurry vision

The effects of Perampanel on tasks involving alertness and vigilance, such as driving, were additive to the effects of alcohol itself.

Multiple doses of Perampanel increased levels of anger, confusion, and depression, particularly when taken with alcohol.

Fycompa may lead to euphoria and other similar feelings in some patients.

What are the most serious side effects of Perampanel?

Serious or life-threatening psychiatric (mental) and behavioral problems: Psychiatric and behavioral problems were seen more frequently in patients treated with Fycompa. The symptoms occurred most often in the early weeks of starting the medication and when higher doses were used. These problems occurred in people with and without a prior history of psychiatric or behavioral problems, more often than in people who took a placebo or inactive drug during the clinical trials of Fycompa.

These reactions are described in the Boxed WARNING bolded below and the Important Safety Information from the package insert.

WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS

  • 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.

  • 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 healthcare 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 FYCOMPA or after discontinuing FYCOMPA.

  • Closely monitor patients 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 (5.1)

Suicidal thoughts or behavior: (Antiepileptic drugs (AEDs), including Fycompa, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Joe, this is from package insert- ? write the same way, or reword to below?)

Seizure medications, including Fycompa, may increase the risk of suicidal thoughts or behavior in people using these medications. People taking seizure medications should be followed carefully for changes in mood, depression, suicidal thoughts or behaviors. Patients and families should talk to their health care providers about any changes in behavior or mood that occur while taking a seizure medication.

Dizziness, gait problems, sleepiness and fatigue: Reports of dizziness, coordination problems, difficulty walking (gait disturbance), and sleepiness or fatigued have been reported in people taking higher daily dosages of Fycompa. These problems happened most often when the dose was first being started and increased. They also occurred more often in older people starting Fycompa.

Falls: More people who were taking higher doses of Fycompa experienced falls than those taking a placebo (inactive drug). These falls were not necessarily related to seizures. Some falls led to serious problems such as head injury or broken bones. Older people taking Fycompa were at greater risk of falls.

Impact of Perampanel on bone health

See package insert for detailed information.  The impact on bone health is unknown at this time.

What else is Perampanel used for?

Fycompa is a seizure medication approved for use as add-on therapy (which means to take in addition to another seizure medication) in people 12 years age or older to treat partial onset seizures.

Partial onset seizures are also called focal seizures that start in one area of the brain. They may stay localized to one area and may be called simple partial or complex partial seizures. Partial seizures may also be called secondary generalized seizures if they spread to larger areas of the brain and lead to a generalized seizure.  

Who should not take Perampanel?
  • People with severe liver and kidney problems
  • People on hemodialysis for kidney problems
Can Perampanel be taken with other medicines?

Because this drug is metabolized through the liver there are specific drug interactions that need to be considered. Fycompa may decrease the effectiveness of progesterone-containing hormone contraceptives. It is also known to decrease levonorgestrel by almost 40%; ethynylestradiol is decreased by 18%. Therefore, considerations for contraception need to be considered. Fycompa itself may have decreased levels when taken with carbamazepine, oxcarbazepine, and topiramate. However, Fycompa may decrease the levels of carbamazepine, clobazam, lamotrigine, valproic acid, but increase the level of oxcarbazepine. Carbamazepine is a known enzyme inducer and it reduces Perampanel levels by almost two-thirds. Therefore, dosing needs to be adjusted when taken with carbamazepine, phenytoin or oxcarbazepine. Perampanel decreases the clearance of oxcarbazepine. It does decrease midazolam levels by 13%. Drugs such as rifampin may decrease Perampanel concentrations. Felbamate may also reduce Perampanel concentration as well. Ketoconazole increases Perampanel by 20% and prolongs its half life by 15%. Fycompa has no impact on Levodopa.

Summary of drug interactions:

  • Oral contraceptives:
    • Fycompa may decrease the effectiveness of progesterone-containing hormone contraceptives.
    • It is also known to decrease levonorgestrel by almost 40%; ethynylestradiol is decreased by 18%.
    • Considerations for contraception need to be considered.
  • Effect on other seizure medications:
    • Decrease levels of carbamazepine, clobazam, lamotrigine, valproic acid, midazolam
    • Increase level of oxcarbazepine
  • Effect on Fycompa:
    • Decreased levels of Fycompa may be caused by carbamazepine, oxcarbazepine, phenytoin, topiramate, felbamate, rifampin
    • Increased levels of Fycompa may be caused by ketoconazole
  • Alcohol and other nervous system depressants:
    • Fycompa when taken with alchohol or other depressant medications increased the effects of alcohol and could cause problems with change in alertness, confusion, or mood.
If a woman takes Perampanel during pregnancy will it hurt the baby?

There is limited data about the use of Fycompa during pregnancy. This drug is labeled by the FDA as a Category C drug. This means that Fycompa should be used during pregnancy only if the potential benefit justifies the potential risk to the baby.

  • Pregnancy: Studies in animals do not indicate any teratogenic effects, but this needs to be proven with more studies as more women use the drug.
  • Breastfeeding: Animal studies (using rats) show that Perampanel or its' metabolites can be excreted in breastmilk. It is not known if Perampanel is excreted in human milk, however.
  • Fertility: There is no known impact on male fertility. The effect on female fertility is not known yet. 
What are the effects of Perampanel on Seniors

Fycompa has not been studied in enough older adults (age 65 and over) to determine its’ safety and effectiveness. Some side effects tended to occur more often in older people, thus the use of this drug in older people should be carefully monitored.

Lower doses of Fycompa may be needed in older adults and the drug should be started slower, with dosage changes made no sooner than 2 weeks. 

What are the dose ranges for Perampanel?

The "best dose" is the amount that works for each person to control seizures without bothersome side effects. The recommended amount may change according to other seizure medications that are also taken. Age and other medical conditions may also affect how the medicine should be dosed.

  • For people not taking enzyme-inducing seizure medications: The dosage range listed in the package insert is 4 to 8 mg per day. Up to 12 mg daily may have some greater improvement in seizures but are likely to cause more side effects.
  • For people also taking enzyme-inducing seizure medications: The dosage range in the package insert is 8 to 12 mg.

Since Fycompa has a long half-life (over 4 days), the drug should be started slowly at 2 mg per day. It is recommended that the dose be increased by 2 mg a day and that changes be made on a weekly basis or slower.

  • People with liver or kidney problems may need different doses and the drug should be started more slowly than for people without these problems.
  • People with other health problems should follow instructions from their doctor or licensed prescriber carefully and follow recommendations for monitoring closely.
Read the package insert of Perampanel

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Fycompa (perampanel) is found at:

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see How to read a package insert.