Perampanel

Perampanel is a prescription medication used for the treatment of partial-onset and tonic-clonic seizures.

• Perampanel is available under the following different brand names: Fycompa

Adult and pediatric dosage

Tablet: Schedule III

• 2mg
• 4mg
• 6mg
• 8mg
• 10mg
• 12mg
• Oral suspension
• 0.5mg/mL

Partial Onset Seizures

Adult dosage

• Initial
  • In absence of concomitant enzyme-inducing antiepileptic drugs (AEDs): 2 mg orally every night at bedtime initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability to 4-8 mg every night at bedtime
• Maintenance
  • Dosage range: 8-12 mg/day
  • The response may occur with 4 mg/day; 12 mg/day resulted in greater seizure rate reductions and a greater substantial increase in side effects

Pediatric dosage

• Children below 4 years: Safety and efficacy not established
• Children above 4 years
  • Initial
    • In absence of enzyme-inducing AEDs: 2 mg orally every night during bedtime; increase by 2 mg/day increments in at least weekly intervals to 4-8 mg every night during bedtime based on clinical response and tolerability
  • Maintenance
    • Dosage range: 8-12 mg/day
    • The response may occur with 4mg/day; 12 mg/day resulted in greater seizure rate reductions and a greater substantial increase in side effects

Tonic-Clonic Seizures

Adult dosage

• Initial
  • In absence of enzyme-inducing AEDs: 2 mg orally every night during bedtime initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability
• Maintenance
  • 8 mg orally every night during bedtime
  • If 8 mg/day is well tolerated but further control is needed, may increase up to 12 mg/day

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Children above 12 years
  • Initial
    • In absence of enzyme-inducing AEDs: 2 mg orally every night during bedtime initially; increase by 2 mg/day increments in at least weekly intervals based on clinical response and tolerability
  • Maintenance
    • 8 mg orally every night during bedtime
    • If 8 mg/day is well tolerated but further seizure control is needed, may increase up to 12 mg/day

Geriatric dosage

• Adults above 65 years: Increase dosage no more frequently than every 2 weeks to target dose

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Perampanel include:

• headache,
• dizziness,
• drowsiness,
• feeling anxious,
• tiredness,
• irritableness,
• nausea,
• vomiting,
• stomach pain,
• bruising,
• weight gain, and
• loss of coordination.

Serious side effects of Perampanel include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• skin rash,
• fever,
• swollen glands,
• muscle aches,
• severe weakness,
• unusual bruising,
• yellowing of the skin or eyes (jaundice),
• mood or behavior changes,
• anxiety,
• fear,
• panic attacks,
• trouble sleeping,
• irritableness,
• agitation,
• hostility,
• aggressiveness,
• restlessness,
• hyperactive (mentally or physically),
• suicidal thoughts,
• severe dizziness,
• spinning sensation,
• lightheadedness,
• trouble walking,
• loss of balance or coordination,
• feeling very weak or tired,
• an accidental fall,
• memory problems,
• confusion, and
• hallucinations

Rare side effects of Perampanel include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Perampanel has no noted severe interactions with the following drugs.
• Perampanel has no noted serious interactions with the following drugs.
• Perampanel has no noted moderate interactions with the following drugs.
• Perampanel has no noted minor interactions with the following drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Perampanel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Perampanel?”

Cautions

Serious psychiatric and behavioral reactions

• Aggression-related adverse reactions were reported at doses of 8 mg and 12 mg per day, these effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks
• Other symptoms included belligerence, affect lability, agitation, and physical assault; some events were reported as serious and life-threatening; homicidal ideation and/or threat also reported postmarketing
• These events occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression
• Some patients experienced worsening of their pre-existing psychiatric conditions; patients with active psychotic disorders and unstable recurrent affective disorders have not been studied
• Combination with alcohol significantly worsened mood and increased anger; patients receiving therapy should avoid the use of alcohol
• Similar serious psychiatric and behavioral events were also reported in patients with a primary generalized tonic-clonic seizure; psychiatric events included paranoia, euphoric mood, agitation, anger, mental status changes, and disorientation/confusional state
• in the postmarketing setting, there have also been reports of psychosis (acute psychosis, hallucinations, delusions, paranoia)and delirium (delirium, confusional state, disorientation, memory impairment) in patients receiving therapy
• Patients, their caregivers, and families should be informed that the drug may increase the risk of psychiatric events; patients should be monitored during treatment and for at least 1 month after the last dose, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases; dose should be reduced if these symptoms occur
• Permanently discontinue therapy for persistent severe or worsening psychiatric symptoms or behaviors and refer for psychiatric evaluation

Suicidal behavior and ideation

• Antiepileptic drugs (AEDs) 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
• The increased risk of suicidal thoughts or behavior with AEDs reported as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed; because assessment did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be determined
• Anyone considering prescribing this drug or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness; epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior; should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated

Neurologic effects

• Dose-related increases in dizziness and disturbance in gait or coordination were reported among patients with a partial-onset seizure; these adverse reactions were also observed in patients with primary generalized tonic-clonic seizures
• Dose-dependent increases in somnolence and fatigue-related events (including fatigue, asthenia, and lethargy) were also reported; adverse reactions occurred mostly during the titration phase; also reported with primary generalized tonic-clonic seizures
• An increased risk of falls, in some cases leading to serious injuries including head injuries and bone fracture, was reported in patients being treated with this drug (with and without concurrent seizures); elderly patients reported to have an increased risk of falls compared to younger adults and pediatric patients
• Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery until the effect is known; patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation when the drug is used with other drugs with sedative properties because of potential additive effect

Drug reaction with eosinophilia and systemic symptoms (DRESS)

• Also known as multiorgan hypersensitivity, DRESS has been reported in patients receiving therapy; DRESS may be fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection; eosinophilia is often present
• Because this disorder is variable in its expression, other organ systems not noted here may be involved; important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, the patient should be evaluated immediately
• Therapy should be discontinued if an alternative etiology for signs or symptoms cannot be established

Withdrawal of antiepileptic drugs

• There is the potential for increased seizure frequency in patients with seizure disorders when antiepileptic drugs are withdrawn abruptly; this drug has a half-life of approximately 105 hours so that even after abrupt cessation, blood levels fall gradually; in epilepsy, clinical trials were withdrawn without down-titration; although a small number of patients exhibited seizures following discontinuation, the data were not sufficient to allow any recommendations regarding appropriate withdrawal regimens
• A gradual withdrawal is generally recommended with antiepileptic drugs, but if withdrawal is a response to adverse events, prompt withdrawal can be considered

Drug interaction overview

• Moderate to strong CYP3A4 inducers (eg, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, primidone, topiramate) may greatly increase clearance, resulting in reduced perampanel plasma concentrations (see Dosage Modifications)

Pregnancy and Lactation

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs); encourage women to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org
• There are no adequate data on the developmental risk associated with use in pregnant women; in animal studies, perampanel induced developmental toxicity in pregnant rats and rabbits at clinically relevant doses

Contraception

• Advise women who are using a levonorgestrel-containing contraceptive to use an additional non-hormonal form (eg, condoms) of contraception while in therapy and for a month after discontinuation

Lactation

• Perampanel and/or its metabolites are present in rat milk and are detected at concentrations higher than that in maternal plasma
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or the underlying maternal condition