perampanel

General

Pronunciation:
per-am-pa-nel


Trade Name(s)

  • Fycompa

Ther. Class.

anticonvulsants

Pharm. Class.

glutamate receptor antagonists

Controlled Substance Schedule: III

Indications

  • Treatment (with or without other anti-epileptic drugs [AEDs]) of partial-onset seizures with or without secondarily generalized seizures.
  • Adjunctive treatment (with other AEDs) of primary generalized tonic-clonic seizures.

Action

Acts as a non-competitive α-amino-3–hydroxy-5–methyl-4–isoxazolepropionic acid (AMPA) antagonist on post-synaptic neuronal glutamate (excitatory) receptors.

Therapeutic Effect(s):

Decreased incidence and severity of partial-onset seizures and primary generalized tonic-clonic seizures.

Pharmacokinetics

Absorption: Rapidly and completely absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 95–96%.

Metabolism and Excretion: Extensively metabolized by CYP3A4/5 enzyme systems; excreted in urine and feces primarily as metabolites.

Half-life: 105 hr.

TIME/ACTION PROFILE

ROUTEONSETPEAKDURATION†
POunknownunknown2 wk
†Duration of effects following cessation.

Contraindication/Precautions

Contraindicated in:

  • Concurrent use of strong CYP450 inducers (other than AEDs);
  • Severe hepatic impairment.

Use Cautiously in:

  • History of homicidal/suicidal ideation or other psychiatric/behavioral issues;
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  • Lactation: Safety not established in breastfeeding;
  • Pedi:  Children <4 yr (safety and effectiveness not established);
  • Geri:  ↑ risk of adverse reactions in older adults; slower titration recommended.

Adverse Reactions/Side Effects

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

Metabolic: weight gain

Neuro: dizziness, drowsiness, headache, aggression, anger, ataxia, balance disorder, fatigue, gait disturbance, hostility, irritability, psychiatric/behavioral problems, suicidal ideation, vertigo

Misc: falls

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Doses >12 mg/day may ↓ effectiveness of  levonorgestrel-containing hormonal contraceptives.
  •  CYP450 inducers  including  carbamazepine,  oxcarbazepine,  phenobarbital,  phenytoin,  primidone, and  topiramate  can ↓ levels and effectiveness; careful monitoring is required especially during initiation and withdrawal. Dosage adjustments may be required.
  • ↑ risk of CNS depression with other  CNS depressants  including  alcohol, sedating  antihistamines,  barbiturates,  benzodiazepines,  opioids, and  sedative/hypnotics.

Drug-Natural Products:

Levels and effectiveness may be ↓ by  St. John's wort ; concurrent use should be avoided.

Route/Dosage

Partial-Onset Seizures

PO (Adults and Children  ≥4 yr): 2 mg once daily at bedtime initially; may ↑ by 2 mg/day at weekly intervals (usual dosage range = 4–12 mg once daily);  Concurrent use of moderate or strong CYP3A4 enzyme-inducers (e.g. phenytoin, carbamazepine, oxcarbazepine): 4 mg once daily at bedtime initially; may ↑ by 2 mg/day at weekly intervals (maximum dose = 12 mg once daily).

PO Geriatric Patients: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (usual dosage range = 4–12 mg once daily);  Concurrent use of moderate or strong CYP3A4 enzyme-inducers (e.g. phenytoin, carbamazepine, oxcarbazepine): 4 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (maximum dose = 12 mg once daily).

Hepatic Impairment 
PO (Adults and Children  ≥4 yr): Mild hepatic impairment: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (maximum dose = 6 mg once daily);  Moderate hepatic impairment: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day after 2 wk up to 4 mg once daily.

Primary Generalized Tonic-Clonic Seizures

PO (Adults and Children  ≥12 yr): 2 mg once daily at bedtime initially; may ↑ by 2 mg/day at weekly intervals (usual dosage range = 8–12 mg once daily);  Concurrent use of moderate or strong CYP3A4 enzyme-inducers (e.g. phenytoin, carbamazepine, oxcarbazepine): 4 mg once daily at bedtime initially; may ↑ by 2 mg/day at weekly intervals (maximum dose = 12 mg once daily).

PO Geriatric Patients: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (usual dosage range = 4–12 mg once daily);  Concurrent use of moderate or strong CYP3A4 enzyme-inducers (e.g. phenytoin, carbamazepine, oxcarbazepine): 4 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (maximum dose = 12 mg once daily).

Hepatic Impairment 
PO (Adults and Children  ≥12 yr): Mild hepatic impairment: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day every 2 wk (maximum dose = 6 mg once daily);  Moderate hepatic impairment: 2 mg once daily at bedtime initially; may ↑ by 2 mg/day after 2 wk up to 4 mg once daily.

Availability (generic available)

Oral suspension: 0.5 mg/mL

Tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg

Assessment

  • Assess location, duration, and characteristics of seizure activity. Institute seizure precautions. Assess response to and continued need for perampanel periodically during therapy.
  • Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior, new or worse aggressive behavior, or depression.
  • Monitor for signs and symptoms of neurologic effects (dizziness, gait disturbance, somnolence, fatigue) during therapy. More common during titration phase and with geriatric patients.
  • Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Implementation

  • PO Administer once daily at bedtime.
    • Shake oral solution well prior to use. Use provided adaptor and graduated oral dosing syringe for accurate dosing.

Patient/Family Teaching

  • Instruct patient to take perampanel as directed. Missed doses should be omitted and dosing resumed the following day. Notify health care professional if more than 1 day of dosing is missed. Medication should be gradually discontinued, do not stop abruptly, to prevent seizures. Advise patient to read the  Medication Guide  prior to starting perampanel and with each Rx refill in case of changes.
  • May cause dizziness, sleepiness, fatigue, and gait disturbance, increasing risk of falls. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Inform patients and families of risk of suicidal thoughts and behavior (behavioral changes, emerging or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm) and aggressive behavior (hostility, anger, anxiety, irritability, being suspicious or distrustful, believing things that are not true). Advise that these should be reported to health care professional immediately.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially carbamazepine, phenytoin, oxcarbazepine, rifampin, and St. John's wort. Advise patient to avoid taking other CNS depressants or alcohol.
  • Rep:  Perampanel decreases efficacy of levonorgestrel; advise patients to use a non-hormonal form of birth control during therapy. Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.

Evaluation/Desired Outcomes

Decreased seizure activity.