Fycompa (Perampanel)
AMPA Receptor Antagonist for Epilepsy – Focal and Generalized Seizures
Quick Facts About Fycompa
Key Takeaways About Fycompa
- First-in-class mechanism: Fycompa is the only approved antiepileptic drug that selectively targets AMPA glutamate receptors, offering a unique approach when other treatments have failed
- Once-daily bedtime dosing: Taken once at bedtime to minimise daytime dizziness and drowsiness, with a long half-life of approximately 105 hours
- Behavioural monitoring required: May cause aggression, anger, irritability and psychiatric symptoms – patients and caregivers should report any mood changes immediately
- Reduces hormonal contraceptive efficacy: Women of childbearing potential need additional or alternative non-hormonal contraception while taking Fycompa
- Gradual dose adjustment: Treatment is started at 2 mg/day and slowly titrated upward at two-week intervals to find the optimal dose, typically 4–12 mg/day
What Is Fycompa and What Is It Used For?
Fycompa (perampanel) is a prescription antiepileptic drug used as adjunctive (add-on) therapy for the treatment of epilepsy. It is indicated for focal (partial-onset) seizures with or without secondary generalisation in patients aged 4 years and older, and for primary generalised tonic-clonic seizures in patients aged 7 years and older.
Perampanel belongs to a unique class of antiepileptic drugs known as selective, non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonists. AMPA receptors are a type of ionotropic glutamate receptor found throughout the central nervous system that mediate fast excitatory synaptic transmission. By selectively blocking these receptors at a site different from the glutamate binding site, perampanel reduces the excitatory signalling that drives seizure activity without completely eliminating normal glutamatergic neurotransmission.
Glutamate is the primary excitatory neurotransmitter in the brain, and excessive glutamate signalling through AMPA receptors plays a central role in the generation and spread of epileptic seizures. Perampanel was specifically designed to target this mechanism, making it the first and currently only approved medication in its class. This novel mechanism of action is particularly valuable for patients whose seizures are not adequately controlled by existing antiepileptic drugs that work through other pathways, such as sodium channel blockers or GABA-enhancing agents.
In focal (partial-onset) seizures, the seizure activity begins in one specific area of the brain. These seizures may remain localised (simple or complex partial seizures) or may spread to involve the entire brain, a process known as secondary generalisation. Fycompa is approved for use as adjunctive therapy – meaning it is added to one or more other antiepileptic drugs – in adults, adolescents (aged 12 years and older), and children (aged 4 to 11 years) with focal seizures.
In primary generalised tonic-clonic seizures, the seizure involves the entire brain from the onset, causing loss of consciousness, muscle stiffening (tonic phase), and rhythmic jerking (clonic phase). Fycompa is approved as adjunctive therapy for these seizures in adults, adolescents (aged 12 years and older), and children (aged 7 to 11 years). Clinical trials have demonstrated that perampanel significantly reduces the frequency of primary generalised tonic-clonic seizures compared with placebo.
Fycompa was first approved by the European Medicines Agency (EMA) in 2012 and by the US Food and Drug Administration (FDA) in the same year. It was developed by Eisai, a Japanese pharmaceutical company with a strong focus on neurology. The drug is approved in more than 70 countries worldwide. According to the International League Against Epilepsy (ILAE), approximately 30% of people with epilepsy do not achieve seizure control with currently available medications, making novel mechanisms of action such as AMPA receptor antagonism an important area of drug development.
What Should You Know Before Taking Fycompa?
Before starting Fycompa, inform your doctor about all medical conditions, particularly liver or kidney problems, a history of substance abuse, psychiatric disorders, or suicidal thoughts. Fycompa is contraindicated in patients with severe liver impairment or moderate to severe kidney impairment.
Contraindications
You should not take Fycompa if any of the following apply to you:
- Allergy to perampanel or any of the inactive ingredients in Fycompa tablets (including lactose monohydrate, low-substituted hydroxypropyl cellulose, povidone, magnesium stearate, hypromellose, talc, macrogol, titanium dioxide, and various iron oxide colourants)
- Previous serious skin reactions to perampanel, including skin peeling, blistering, or mouth sores
- Severe liver impairment – the drug is extensively metabolised by the liver and cannot be safely used in severe hepatic disease
- Moderate or severe kidney impairment – insufficient data on safety in these populations
Warnings and Precautions
Before and during treatment with Fycompa, be aware of the following important safety considerations:
Fycompa may cause significant psychiatric and behavioural changes including aggression, anger, irritability, anxiety, confusion, and violent behaviour. In rare cases, psychotic disturbances such as hallucinations, abnormal thinking, and loss of contact with reality have been reported. These effects can occur at any time during treatment but are more common during dose increases. Patients, family members, and caregivers should be vigilant for any unusual changes in mood or behaviour and should contact a healthcare provider immediately if such changes occur.
As with all antiepileptic drugs, a small number of patients treated with Fycompa have reported suicidal thoughts and behaviour. Patients should seek immediate medical attention if they experience thoughts of self-harm or suicide. Family members and caregivers should monitor for the emergence of such symptoms, especially during treatment initiation and dose changes.
Fycompa has been associated with serious, potentially life-threatening skin reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS). DRESS typically presents as flu-like symptoms, widespread rash, fever, elevated liver enzymes, and swollen lymph nodes. SJS may begin as red target-shaped marks on the trunk, often with central blisters, along with sores on the mouth, throat, nose, genitals, and eyes. If any of these symptoms develop, stop taking Fycompa immediately and seek urgent medical care.
Dizziness and somnolence: Fycompa frequently causes dizziness and drowsiness, particularly at the start of treatment and during dose increases. These effects increase the risk of falls, especially in older adults. Patients should avoid activities requiring alertness, such as driving or operating machinery, until they know how the medication affects them.
Liver enzyme elevations: Increases in liver enzyme levels have been reported in some patients taking Fycompa in combination with other antiepileptic drugs. Your doctor may perform regular blood tests to monitor liver function during treatment.
History of substance abuse: Patients with a history of alcohol or drug dependence should inform their doctor before starting Fycompa, as this may influence treatment decisions and monitoring requirements.
Falls: Fycompa may increase the risk of falls due to its effects on balance and coordination. This is particularly relevant for elderly patients, who should exercise extra caution. The risk of falls may also be related to the underlying epilepsy condition itself.
Pregnancy and Breastfeeding
Fycompa is not recommended during pregnancy unless the potential benefit justifies the potential risk to the foetus. Women of childbearing potential must use reliable contraception during treatment and for one month after stopping Fycompa. Importantly, Fycompa can reduce the effectiveness of certain hormonal contraceptives, particularly those containing levonorgestrel, so alternative or additional non-hormonal methods (such as condoms or intrauterine devices) should be used.
It is not known whether perampanel or its metabolites pass into breast milk. Your doctor will assess the risks and benefits of continuing Fycompa while breastfeeding. If you are pregnant, planning to become pregnant, or breastfeeding, discuss your treatment options thoroughly with your healthcare provider. Never stop antiepileptic treatment abruptly without medical supervision, as this may trigger severe or prolonged seizures.
Driving and Operating Machinery
Fycompa may significantly impair your ability to drive or operate machinery, particularly due to dizziness, drowsiness, and effects on coordination. Do not drive or use machinery until you are certain that Fycompa does not affect your alertness and reaction time. Additionally, discuss with your doctor how your epilepsy itself may affect your ability to drive, as driving regulations for people with epilepsy vary by country.
Consuming alcohol while taking Fycompa can further impair alertness and increase feelings of anger, confusion, and sadness. Patients should exercise caution with alcohol consumption during treatment.
How Does Fycompa Interact with Other Drugs?
Fycompa interacts with several commonly used medications, including other antiepileptic drugs, hormonal contraceptives, certain antibiotics, and antifungal agents. Some of these interactions can significantly reduce Fycompa’s effectiveness or alter the levels of co-administered drugs. Always inform your doctor about all medicines you are taking.
Perampanel is primarily metabolised by the cytochrome P450 enzyme CYP3A4 in the liver. Drugs that induce or inhibit this enzyme can significantly alter perampanel blood levels. Conversely, perampanel itself can affect the metabolism of other drugs, particularly those processed by CYP3A4 or conjugation pathways.
Major Interactions
The following drugs have clinically significant interactions with Fycompa and may require dose adjustments or alternative treatment choices:
| Drug | Type | Effect | Action Required |
|---|---|---|---|
| Carbamazepine | CYP3A4 inducer | Reduces perampanel levels by up to two-thirds | Higher Fycompa dose may be needed; monitor response |
| Oxcarbazepine | CYP3A4 inducer | Significantly reduces perampanel blood levels | Dose adjustment may be necessary |
| Phenytoin | CYP3A4 inducer | Reduces perampanel levels by up to two-thirds | Higher Fycompa dose may be needed; monitor response |
| Rifampicin | Strong CYP3A4 inducer | Substantially reduces perampanel exposure | Dose adjustment likely required |
| St John’s Wort | CYP3A4 inducer | May reduce perampanel blood levels | Avoid concurrent use or adjust dose |
| Levonorgestrel | Hormonal contraceptive | Fycompa reduces levonorgestrel efficacy | Use additional non-hormonal contraception |
Other Notable Interactions
The following interactions are also clinically relevant but may be less severe:
| Drug | Type | Effect | Action Required |
|---|---|---|---|
| Felbamate | Antiepileptic | May affect perampanel blood levels | Dose adjustment may be needed |
| Ketoconazole | CYP3A4 inhibitor | May increase perampanel blood levels | Monitor for increased side effects |
| Midazolam | Benzodiazepine | Perampanel may reduce midazolam efficacy | Midazolam dose may need adjustment |
| Alcohol | CNS depressant | Additive sedation, impaired coordination, worsened mood effects | Avoid or limit alcohol consumption |
Fycompa can reduce the effectiveness of hormonal contraceptives, including oral pills, implants, injections, and patches. Women of childbearing potential should use additional or alternative non-hormonal contraception (such as condoms or an intrauterine device) during treatment and for one month after stopping Fycompa. Discuss the most appropriate contraceptive method with your doctor.
What Is the Correct Dosage of Fycompa?
Fycompa is taken once daily at bedtime. The starting dose is usually 2 mg/day for adults and adolescents (or 1 mg/day for smaller children), with gradual dose increases of 2 mg at two-week intervals. The typical maintenance dose ranges from 4 to 12 mg/day depending on age, weight, tolerability, and seizure response.
Fycompa tablets should be swallowed whole with a glass of water and can be taken with or without food. The tablets should not be chewed, crushed, or split, as they lack a break line and cannot be divided accurately. All dose adjustments should be made under the supervision of your prescribing physician, and it may take several weeks to find the optimal dose for you.
Adults and Adolescents (12 Years and Older)
For the treatment of both focal seizures and primary generalised tonic-clonic seizures in adults and adolescents aged 12 years and older:
Standard Adult Dosing
- Starting dose: 2 mg once daily at bedtime
- Dose titration: Increase by 2 mg at intervals of at least 2 weeks
- Maintenance dose: 4–8 mg/day (may be increased to 12 mg/day based on response)
- Maximum dose: 12 mg/day
- Liver impairment (mild to moderate): Maximum 8 mg/day; titrate at intervals of at least 2 weeks
Children (4 to 11 Years)
Dosing in children depends on body weight and the type of seizure being treated. The following table summarises the recommended dosing:
| Parameter | ≥30 kg | 20–<30 kg | <20 kg |
|---|---|---|---|
| Starting dose | 2 mg/day | 1 mg/day | 1 mg/day |
| Maintenance dose | 4–8 mg/day | 4–6 mg/day | 2–4 mg/day |
| Maximum dose | 12 mg/day | 8 mg/day | 6 mg/day |
| Titration increment | 2 mg every ≥2 weeks | 1 mg every ≥2 weeks | 1 mg every ≥2 weeks |
For children with mild to moderate liver impairment, the maximum recommended dose is 4 mg/day regardless of body weight, and dose titration should occur at intervals of at least two weeks. Fycompa is not recommended for children under 4 years of age for focal seizures, or under 7 years of age for generalised seizures, as safety and efficacy have not been established in these younger age groups.
Elderly Patients
No specific dose adjustment is required solely based on age. However, elderly patients are generally more susceptible to the central nervous system effects of Fycompa, including dizziness, somnolence, and impaired coordination, which increase the risk of falls. Careful dose titration and close monitoring are recommended. The prescribing physician should consider the overall clinical condition, including renal and hepatic function, concomitant medications, and fall risk when determining the appropriate dose.
Missed Dose
If you forget to take a dose of Fycompa, do not take a double dose to compensate. Simply skip the missed dose and take your next dose at the usual time. If you have missed fewer than 7 consecutive days of treatment, continue taking your daily dose as prescribed by your doctor. If you have missed more than 7 consecutive days, contact your doctor immediately, as your dose may need to be re-titrated from a lower starting dose to avoid breakthrough seizures or adverse effects from resuming at the full dose.
Overdose
If you take more Fycompa than prescribed, seek immediate medical attention or contact your nearest emergency department. Symptoms of overdose may include confusion, agitation, aggressive behaviour, and reduced level of consciousness. There is no specific antidote for perampanel; treatment is supportive and may include monitoring of vital signs, gastric decontamination if appropriate, and symptomatic management of any adverse effects.
Never stop taking Fycompa suddenly without consulting your doctor. Abrupt discontinuation of antiepileptic drugs can lead to an increase in seizure frequency or the occurrence of status epilepticus, a life-threatening condition of prolonged seizures. Your doctor will gradually reduce your dose over time if treatment needs to be stopped.
What Are the Side Effects of Fycompa?
Like all medicines, Fycompa can cause side effects, although not everybody experiences them. The most common side effects are dizziness and drowsiness. Serious but less common side effects include aggression, suicidal thoughts, and severe skin reactions (DRESS, SJS). Seek immediate medical attention if you experience severe symptoms.
The side effects of Fycompa are typically dose-dependent, meaning they occur more frequently and with greater severity at higher doses. Most side effects are mild to moderate and tend to improve as your body adjusts to the medication. However, some side effects can be serious and require immediate medical attention.
Very Common
Affects more than 1 in 10 patients
- Dizziness
- Somnolence (drowsiness or excessive sleepiness)
Common
Affects 1 in 10 to 1 in 100 patients
- Increased or decreased appetite
- Weight gain
- Aggression, anger, irritability
- Anxiety or confusion
- Difficulty walking or balance problems (ataxia, gait disturbance)
- Slurred speech (dysarthria)
- Blurred vision or double vision (diplopia)
- Vertigo (spinning sensation)
- Nausea
- Back pain
- Fatigue
- Falls
Uncommon
Affects 1 in 100 to 1 in 1,000 patients
- Suicidal thoughts or suicide attempts
- Hallucinations (seeing, hearing, or feeling things that are not there)
- Psychotic disturbances (abnormal thinking and/or loss of contact with reality)
Not Known
Frequency cannot be estimated from available data
- DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) – widespread rash, fever, elevated liver enzymes, abnormal blood counts, swollen lymph nodes
- Stevens-Johnson Syndrome (SJS) – red target-shaped marks, blistering, skin peeling, sores on mouth, throat, nose, genitals, and eyes, preceded by fever and flu-like symptoms
The psychiatric and behavioural side effects of Fycompa deserve special attention. Aggression and irritability are among the more commonly reported adverse effects and can range from mild irritability to severe hostility. These effects may be more pronounced in patients with a prior history of psychiatric conditions. In clinical trials, aggression was reported in approximately 3–12% of patients, with higher rates observed at doses of 8 mg/day and above.
Dizziness and somnolence, while common, are typically most pronounced during the initial weeks of treatment and during dose increases. Taking Fycompa at bedtime is recommended to minimise the impact of these effects on daily activities. However, patients should be aware that dizziness and drowsiness may persist into the following day, particularly at higher doses.
Falls are a notable concern, especially in elderly patients. The combination of dizziness, impaired balance, and somnolence can significantly increase fall risk. Patients should take precautions such as rising slowly from sitting or lying positions, using handrails on stairs, and avoiding situations where a fall could cause serious injury.
Stop taking Fycompa and contact your doctor or seek emergency care immediately if you experience: severe skin rash with fever and swollen glands (possible DRESS syndrome), red target-shaped marks or blistering skin (possible Stevens-Johnson Syndrome), thoughts of self-harm or suicide, or severe behavioural changes including extreme aggression or psychotic symptoms.
How Should You Store Fycompa?
Fycompa tablets should be stored at room temperature in their original packaging, out of reach and sight of children. No special storage conditions are required. Do not use the tablets after the expiry date printed on the packaging.
Keep Fycompa tablets in their original blister packaging to protect them from moisture and light until you are ready to take a dose. There are no specific temperature requirements; standard room temperature storage is appropriate. Always check the expiry date before taking a tablet – the expiry date refers to the last day of the indicated month.
Do not dispose of unused or expired medications through household waste or the sewerage system. Return any remaining tablets to your pharmacist for safe disposal in accordance with local environmental protection regulations. Proper medication disposal helps prevent environmental contamination and reduces the risk of accidental ingestion by children, pets, or others.
What Does Fycompa Contain?
Each Fycompa film-coated tablet contains perampanel as the active ingredient, available in six strengths: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg. The tablets also contain lactose monohydrate and various inactive excipients. Each strength is colour-coded for easy identification.
The active ingredient in Fycompa is perampanel. Each film-coated tablet contains either 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, or 12 mg of perampanel.
Inactive Ingredients
The tablet core of the 2 mg and 4 mg tablets contains: lactose monohydrate, low-substituted hydroxypropyl cellulose, povidone, and magnesium stearate (E470b). The 6 mg, 8 mg, 10 mg, and 12 mg tablets also contain microcrystalline cellulose in addition to these ingredients.
The film coating of all strengths contains: hypromellose 2910, talc, macrogol 8000, titanium dioxide (E171), and various colour-specific dyes as detailed below.
| Strength | Colour | Imprint | Colourants |
|---|---|---|---|
| 2 mg | Orange | E275 / 2 | Yellow iron oxide (E172), red iron oxide (E172) |
| 4 mg | Red | E277 / 4 | Red iron oxide (E172) |
| 6 mg | Pink | E294 / 6 | Red iron oxide (E172) |
| 8 mg | Purple | E295 / 8 | Red iron oxide (E172), black iron oxide (E172) |
| 10 mg | Green | E296 / 10 | Yellow iron oxide (E172), FD&C blue No. 2 indigo carmine aluminium lake (E132) |
| 12 mg | Blue | E297 / 12 | FD&C blue No. 2 indigo carmine aluminium lake (E132) |
All Fycompa tablets are round, biconvex, and film-coated. They are available in pack sizes of 7, 28, 84, and 98 tablets (the 2 mg tablets are available in 7, 28, and 98 tablets). Not all pack sizes may be available in every country.
Fycompa tablets contain lactose monohydrate. Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should consult their doctor before taking this medicine.
Frequently Asked Questions About Fycompa
Fycompa (perampanel) is an antiepileptic medication used as add-on therapy for epilepsy. It treats focal (partial-onset) seizures with or without secondary generalisation in adults, adolescents, and children aged 4 years and older. It also treats primary generalised tonic-clonic seizures in adults, adolescents, and children aged 7 years and older. It is always used in combination with other antiepileptic drugs, not as monotherapy.
The most common side effects of Fycompa (affecting more than 1 in 10 patients) are dizziness and drowsiness (somnolence). Common side effects (affecting up to 1 in 10 patients) include appetite changes, weight gain, aggression, irritability, anxiety, confusion, balance problems, slurred speech, blurred or double vision, vertigo, nausea, back pain, fatigue, and falls. Taking Fycompa at bedtime helps minimise daytime dizziness and drowsiness.
Yes, Fycompa can cause significant mood and behavioural changes, including aggression, anger, irritability, anxiety, and confusion. In uncommon cases, it may cause suicidal thoughts, hallucinations, or psychotic disturbances. These effects can occur at any time during treatment but are more likely during dose increases. Patients and their family members or caregivers should monitor closely for any unusual behavioural changes and report them to a doctor immediately.
Take Fycompa once daily at bedtime. Swallow the tablet whole with a glass of water – do not chew, crush, or split it. You can take it with or without food. Your doctor will start you on a low dose (usually 2 mg/day) and gradually increase it every two weeks until the best dose for you is found, typically between 4 and 12 mg per day. Never change your dose or stop taking Fycompa without consulting your doctor first.
Yes, Fycompa can reduce the effectiveness of certain hormonal contraceptives, particularly those containing levonorgestrel. Women of childbearing potential should use additional or alternative non-hormonal contraception methods (such as condoms or an intrauterine device) while taking Fycompa and for one month after stopping treatment. Discuss the most appropriate contraceptive method with your prescribing doctor.
If you miss a dose, do not take a double dose. Simply skip the missed dose and take your next dose at the usual time. If you have missed fewer than 7 consecutive days, continue your regular dosing. If you have missed more than 7 consecutive days, contact your doctor immediately, as you may need to restart at a lower dose and re-titrate slowly to avoid adverse effects.
References and Sources
This article is based on the following peer-reviewed sources, clinical guidelines, and regulatory assessments:
- European Medicines Agency (EMA). Fycompa (perampanel) – Summary of Product Characteristics (SmPC). Updated 2023. Available at: ema.europa.eu/en/medicines/human/EPAR/fycompa
- US Food and Drug Administration (FDA). Fycompa Prescribing Information. Eisai Inc. Updated 2023. Available at: accessdata.fda.gov
- French JA, Krauss GL, Biton V, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012;79(6):589–596. doi:10.1212/WNL.0b013e3182635735
- Krauss GL, Serratosa JM, Villanueva V, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78(18):1408–1415. doi:10.1212/WNL.0b013e318254473a
- French JA, Krauss GL, Steinhoff BJ, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54(1):117–125. doi:10.1111/j.1528-1167.2012.03638.x
- Wechsler RT, Li G, French J, et al. Adjunctive perampanel for primary generalized tonic-clonic seizures: a randomized, double-blind, placebo-controlled phase III trial (Study 332). Epilepsia. 2019;60(8):1697–1706. doi:10.1111/epi.16101
- International League Against Epilepsy (ILAE). ILAE classification of the epilepsies and ILAE treatment guidelines. Epilepsia. 2022. Available at: ilae.org
- Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Currents. 2011;11(2):56–63. doi:10.5698/1535-7511-11.2.56
- World Health Organization (WHO). Epilepsy: a public health imperative. 2019. Available at: who.int
- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults: diagnosis and management. NICE guideline NG217. Updated 2024. Available at: nice.org.uk/guidance/ng217
Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which consists of licensed physicians and clinical pharmacologists with expertise in neurology and epilepsy treatment.
iMedic Medical Editorial Team – Specialists in neurology, epileptology, and clinical pharmacology
iMedic Medical Review Board – Independent panel of medical experts reviewing content according to ILAE, EMA, and NICE guidelines
All content on iMedic is evidence-based and follows the GRADE framework for evaluating medical evidence. We adhere to the principles of Experience, Expertise, Authoritativeness, and Trustworthiness (E-E-A-T). This article has evidence level 1A, based on systematic reviews and randomised controlled trials. We have no conflicts of interest and receive no pharmaceutical company funding. For more information, see our Editorial Standards.