perampanel

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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Metab: weight gain

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

Misc: falls

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.

Availability ⬆ ⬇

(Generic available)

Oral suspension: 0.5 mg/mL
Tablets: 2 mg; 4 mg; 6 mg; 8 mg; 10 mg; 12 mg

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.

US Brand Names ⬆ ⬇

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 effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: anticonvulsants

Pharmacologic Classification: glutamate receptor antagonists

Pharmacokinetics ⬆ ⬇

Absorption: Rapidly and completely absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 95–96%.

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

Half-Life: 105 hr.

Contr. Subst. Schedule ⬆ ⬇

Schedule III (C-III)

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION‡
PO	unknown	unknown	2 wk

‡Duration of effects following cessation.

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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇