Fycompa (perampanel)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Perampanel, a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, is an anticonvulsant.
Perampanel, a noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, is an anticonvulsant. The exact mechanism of action by which perampanel exerts its anticonvulsant effects remains to be fully elucidated; however, the drug is known to inhibit AMPA-type glutamate receptors, a class of ionotropic glutamate receptors that mediate fast excitatory neurotransmission and play an important role in the generation and spread of epileptic seizures. In vitro studies indicate that perampanel selectively and noncompetitively inhibits AMPA receptors on postsynaptic neurons, thereby reducing excessive glutamatergic activity and neuronal excitation.
Increased levels of glutamate, the principal excitatory neurotransmitter in the CNS, have been implicated in a variety of neurologic disorders caused by increased excitatory neurotransmission. Perampanel is highly selective for AMPA glutamate receptors and has little or no inhibitory effect on the N-methyl-d-aspartate (NMDA) and kainate ionotropic glutamate receptors. The drug has demonstrated a broad spectrum of anticonvulsant activity in various animal models.
Perampanel is rapidly and completely absorbed following oral administration; peak plasma concentrations are attained within approximately 0.5-2.5 hours under fasting conditions. The bioavailability of the oral suspension is comparable to that of the tablets under steady-state conditions. Administration with a high-fat meal delayed time to peak plasma concentration by approximately 1-3 hours and reduced peak plasma concentrations of the drug by 11-40%, but did not affect the extent of absorption.
Perampanel is extensively metabolized in the liver, primarily by oxidation followed by glucuronidation. In vitro studies indicate that the oxidative metabolism of perampanel is principally mediated by cytochrome P-450 (CYP) isoenzymes 3A4/5 and, to a lesser extent, by CYP1A2 and CYP2B6, although other CYP-mediated pathways may be involved. Following administration of a radiolabeled dose of perampanel in healthy geriatric individuals, approximately 22% of the dose was recovered in urine and 48% in feces mainly as oxidative and conjugated metabolites.
Perampanel is approximately 95-96% protein bound (mainly to albumin and alpha1-acid glycoprotein). The elimination half-life of the drug is approximately 105 hours.
USES: Perampanel is used to treat certain types of seizures (including focal and generalized tonic-clonic seizures).
Generic name: perampanel
Pronunciation: (per-AM-pa-nel)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Fycompa
Indications
The following indications are listed for Fycompa:
- Focal Epilepsy
- Tonic-Clonic Epilepsy Treatment Adjunct
Also known as: Cortical Epilepsy, Focal Seizures, Grand Mal Epilepsy Treatment Adjunct, Local Epilepsy, Partial Epilepsy, Partial Onset Seizures, Partial Seizures, Tonic-Clonic Seizures Treatment Adjunct.
Dosing
Initial dosage recommendations for perampanel vary based on whether a moderate or potent cytochrome P-450 (CYP) 3A4 enzyme-inducing drug (e.g., carbamazepine, oxcarbazepine, phenytoin) is used concomitantly. Such CYP3A4-inducing drugs can reduce plasma concentrations, and thus efficacy, of perampanel. (See Drug Interactions: Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes.)
Perampanel is administered orally as tablets or oral suspension. The drug usually is administered once daily at bedtime and may be given without regard to food. (See Description.) Bioavailability of the commercially available oral suspension is comparable to that of the tablets, and the dosage forms may be used interchangeably.
When discontinuing any anticonvulsant therapy, gradual withdrawal is recommended to minimize the potential for increased seizure frequency in patients with seizure disorders. However, the manufacturer states that there are insufficient data to make specific recommendations regarding withdrawing perampanel. Because of its prolonged half-life (approximately 105 hours), plasma concentrations are expected to decline gradually even after abrupt discontinuance. If discontinuance of perampanel is necessary because of adverse effects, prompt withdrawal of the drug may be considered. (See Discontinuance of Anticonvulsants under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Patients currently receiving or beginning therapy with perampanel and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Monitoring for adverse neuropsychiatric effects is recommended in patients receiving perampanel, especially during the initial titration period (or any other time dosage is increased) and when high dosages (e.g., 12 mg daily) of the drug are used. If any neuropsychiatric manifestations occur, dosage of perampanel should be reduced or therapy discontinued, depending on the severity of the reaction. (See Serious Psychiatric and Behavioral Reactions under Warnings/Precautions: Warnings, in Cautions.)
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Perampanel is principally metabolized by cytochrome P-450 (CYP) isoenzyme 3A4/5 and, to a lesser extent, by CYP1A2 and CYP2B6, although other CYP-mediated pathways may be involved.
Perampanel is a weak inhibitor of CYP2C8 and 3A4, and a weak inducer of CYP2B6 and 3A4/5 in vitro. The drug does not appear to inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, and 2E1 nor induce CYP1A2.
Perampanel is neither a substrate nor substantial inhibitor of the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); organic anion transport proteins (OATP) 1B1 and 1B3; organic anion transporters 1, 2, 3, and 4; and organic cation transporters 1, 2, and 3. Perampanel has weak inhibitory effects on uridine diphosphate-glucuronosyltransferase (UGT) 1A9 and 2B7 and does not appear to inhibit UGT1A1, 1A4, and 1A6. The drug has been shown to induce UGT1A1 and 1A4.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of perampanel.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 4% of patients with partial-onset seizures receiving perampanel in 3 controlled clinical trials and more frequently with the drug than with placebo include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, gait disturbance, and balance disorder.
Adverse effects reported in at least 10% of patients with primary generalized tonic-clonic seizures receiving perampanel in a controlled clinical trial and more frequently with the drug than with placebo include dizziness, fatigue, headache, somnolence, and irritability.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of perampanel have not been established in pediatric patients younger than 12 years of age. A total of 72 adolescents 12-16 years of age were included in the controlled partial-onset seizure trials and 11 adolescents 12-16 years of age were included in the study evaluating primary generalized tonic-clonic seizures with an additional 6 pediatric patients in the open-label extension of the study. In the 3 placebo-controlled studies of perampanel in patients with partial seizures, aggression was observed more frequently in adolescents than in adults receiving the drug. (See Serious Psychiatric and Behavioral Reactions under Warnings/Precautions: Warnings, in Cautions.)
There are no adequate data in humans to determine if there is any risk associated with the use of perampanel during pregnancy; in animal reproductive studies, developmental toxicity (e.g., visceral abnormalities, decreased fetal weight gain, delayed sexual maturation) was observed at clinically relevant doses.
Women who are taking perampanel during pregnancy should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or http://www.aedpregnancyregistry.org.
Perampanel and/or its metabolites are distributed into milk in rats at concentrations higher than those in maternal plasma; it is not known whether the drug is distributed into human milk. The effects of perampanel on the nursing infant or on milk production also are not known. The known benefits of breast-feeding should be considered along with the mother's clinical need for perampanel and any potential adverse effects on the infant from the drug or underlying maternal condition.
There is insufficient experience in patients 65 years of age and older to establish efficacy and safety of perampanel in this population. Geriatric patients treated with the drug appear to be at increased risk of adverse neurologic effects (e.g., dizziness, gait disturbances, somnolence, fatigue) compared with younger adults and adolescents. In addition, the risk of falls appears to be greater in geriatric patients. Because of a greater likelihood of such adverse reactions in geriatric patients, dosage of perampanel should be titrated gradually in patients 65 years of age and older.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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