Perampanel

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 

Indications

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.  

Forms

Please see package insert.

Dosing

Please see package insert.

Mechanisms of actions of Perampanel

Perampanel is a 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.

Clinical Pharmacology of Perampanel

The pharmacology of Perampanel has been studied in healthy adult subjects with partial onset seizures, as well as in other neurological and medical conditions. Perampanel is easily absorbed after oral administration with no evidence of first pass metabolism. When taken with food peak concentrations delayed by two hours. The drug is extensively metabolized via primary oxidation and sequential glucuronidation in the liver. Primary metabolism is mediated by CYP3A and this means that there are some aspects of drug interactions that one will need to consider. The drug has linear pharmacokinetics and there is a linear relationship between dose and concentration over the dose range of 2-12 mg. per day.

Efficacy of Perampanel

See package insert.

Common side effects of Perampanel

The drug does have some known adverse effects associated with this drug. The most common ones are anxiety, confusion, imbalance, double vision, dizziness, gastrointestinal distress or nausea, imbalance – some of which may lead to falls on some occasions, and increased weight. 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. Thus, the drug will be a scheduled in the United States. Final labeling and information is not yet available.

Drug Interactions

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.

Serious Side effects of Perampanel

See package insert.

Impact of Perampanel on bone health

See package insert.

Other Uses of Perampanel

Fycompa has only been approved by the FDA for use as add-on treatment of partial seizures in people age 12 and older.

Perampanel Contraindications

See package insert.

Perampanel Interactions with other medications

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.

Perampanel and Pregnancy

There is limited data with regards to pregnancy experience with Fycompa. Studies in animals do not indicate any teratogenic effects but this is something that needs to be proven with more studies as more individuals use the drug. With regards to breastfeeding, studies in lactating rats have shown excretion of Perampanel and/or its metabolites in milk. It is not known whether Perampanel is excreted in human milk, however. It is important to understand those impacts when making a decision. With regards to fertility, there is no impact on male fertility and the effect of Perampanel in human fertility has not been established.

Perampanel effects on Seniors

See package insert.

Perampanel Dosing and titration

See package insert.

Perampanel Package insert

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.

Our Mission

The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
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