Version July 2025
Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking perampanel. These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression.
Advise patients and caregivers to contact a health care provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking perampanel or after discontinuing perampanel. Closely monitor patients, particularly during the titration period and at higher doses. Reduce perampanel if these symptoms occur, and discontinue the drug immediately if symptoms are severe or are worsening.
Note: Reduce the dosage in patients who experience serious psychiatric or behavioral reactions; discontinue immediately if symptoms are severe or worsening. Tablets and oral suspension may be used interchangeably.
Partial-onset seizures: Oral:
Patients not receiving enzyme-inducing AED regimens: Initial: 2 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Recommended maintenance dose: 8 to 12 mg once daily at bedtime; some patients may respond to 4 mg once daily; 12 mg once daily has resulted in somewhat greater reductions in seizure rates in some patients but with substantial increase in side effects.
Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine): Initial: 4 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Maintenance dose has not been established; highest dose used in clinical trials was 12 mg once daily.
Primary generalized tonic-clonic seizures (adjunct): Oral:
Patients not receiving enzyme-inducing AED regimens: Initial: 2 mg once daily at bedtime; may increase dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Recommended maintenance dose: 8 mg once daily at bedtime; if tolerated and further seizure control is needed, may increase up to 12 mg once daily (maximum dose: 12 mg once daily).
Patients receiving enzyme-inducing AED regimens (eg, phenytoin, carbamazepine, oxcarbazepine): Initial 4 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Maintenance dose has not been established; highest dose used in clinical trials was 12 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 49 mL/minute: No dosage adjustment necessary; monitor closely and consider slower titration based on response and tolerability.
CrCl <30 mL/minute: Use not recommended (has not been studied).
Hemodialysis: Use not recommended (has not been studied).
Mild impairment (Child-Pugh class A): Initial 2 mg once daily; may increase daily dose by 2 mg once daily no more frequently than every 2 weeks based on response and tolerability. Maximum: 6 mg once daily
Moderate impairment (Child-Pugh class B): Initial 2 mg once daily; may increase daily dose by 2 mg once daily no more frequently than every 2 weeks based on response and tolerability. Maximum: 4 mg once daily
Severe impairment (Child-Pugh class C): Use not recommended (has not been studied)
Refer to adult dosing. Increase dose no more frequently than every 2 weeks.
(For additional information see "Perampanel: Pediatric drug information")
Note: Dosing should be individualized based upon response and tolerability. Reduce the dosage in patients who experience serious psychiatric or behavioral reactions; discontinue immediately if symptoms are severe or worsening.
Partial seizures; adjunct or monotherapy: Children ≥4 years and Adolescents: Oral:
Patients not receiving moderate or strong CYP3A4 inducers: Initial: 2 mg once daily at bedtime; may increase daily dose by 2 mg increments no more frequently than at weekly intervals; recommended maintenance dose range: 8 to 12 mg once daily at bedtime; some patients may respond to doses of 4 mg/day. Although 12 mg doses showed somewhat greater efficacy (reduction in seizure rate) in some patients, the 12 mg dose was associated with substantially higher adverse effects; maximum daily dose: 12 mg/day.
Patients receiving moderate or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, oxcarbazepine): Initial: 4 mg once daily at bedtime; may increase daily dose by 2 mg increments no more frequently than at weekly intervals; target maintenance dose range not established; maximum reported dose is 12 mg/day. Monitor patients closely for response and tolerability when inducer is being introduced or withdrawn from therapeutic regimen; perampanel dosing adjustment may be necessary.
Primary generalized tonic-clonic seizures (adjunct): Children ≥12 years and Adolescents: Oral:
Patients not receiving moderate or strong CYP3A4 inducers: Initial: 2 mg once daily at bedtime; may increase dose by 2 mg once daily no more frequently than at weekly intervals based on response and tolerability. Recommended maintenance dose: 8 mg once daily at bedtime; some patients may require 12 mg once daily at bedtime for further seizure control and if tolerated; maximum daily dose: 12 mg/day
Patients receiving moderate or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, oxcarbazepine): Initial: 4 mg once daily at bedtime; may increase daily dose by 2 mg once daily no more frequently than at weekly intervals; individualize dose based on response and tolerability; in trials, the maximum reported dose was 12 mg/day. Monitor patients closely for response and tolerability when inducer is being introduced or withdrawn from therapeutic regimen; perampanel dosing adjustment may be necessary.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥4 years and Adolescents:
Mild impairment: No dosage adjustment necessary.
Moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution, monitor closely, and consider slower titration based on response and tolerability.
Severe impairment: Use not recommended (has not been studied).
Hemodialysis: Use not recommended (has not been studied).
Children ≥4 years and Adolescents:
Mild impairment: Initial: 2 mg once daily; may increase daily dose by 2 mg no more frequently than every 2 weeks based on response and tolerability. Maximum daily dose: 6 mg/day
Moderate impairment: Initial: 2 mg once daily; may increase daily dose by 2 mg after 2 weeks based on response and tolerability. Maximum daily dose: 4 mg/day
Severe impairment: Use not recommended (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Many adverse effects are dose-related. Frequency not always defined.
Cardiovascular: Peripheral edema (2%)
Central nervous system: Dizziness (16% to ≤47%), vertigo (3% to ≤47%), hostility (≤12% to ≤20%), aggressive behavior (2% to ≤20%), drowsiness (9% to 18%), abnormal gait (4% to 16%), fatigue (8% to 15%), headache (12% to 13%), irritability (2% to 12%), falling (5% to 10%), ataxia (≤8%), equilibrium disturbance (3% to 5%), anxiety (2% to 5%), dysarthria (1% to 4%), hypoesthesia (3%), hypersomnia (1% to 3%), anger (1% to 3%), memory impaired (2%), paresthesia (2%), confusion (1% to 2%), euphoria (≤2%), mood changes (1% to 2%), agitation, altered mental status, delusion, disorientation, emotional lability, homicidal ideation, paranoia, psychiatric disturbance (worsening)
Dermatologic: Skin rash (4%)
Endocrine & metabolic: Weight gain (4% to 9%), hyponatremia (2%)
Gastrointestinal: Vomiting (4% to 9%), nausea (6% to 8%), abdominal pain (5%), constipation (3%)
Genitourinary: Urinary tract infection (4%)
Hematologic & oncologic: Bruise (2% to 6%)
Neuromuscular & skeletal: Back pain (5%), sprain (4%), myalgia (3%), arthralgia (2% to 3%), limb pain (2% to 3%), musculoskeletal pain (2%), weakness (2%)
Ophthalmic: Blurred vision (3% to 4%), diplopia (3%)
Respiratory: Cough (4%), upper respiratory tract infection (4%), oropharyngeal pain (2%)
Miscellaneous: Head trauma (3%), laceration (2%), limb injury (1% to 2%)
<1%, postmarketing, and/or case reports: Acute psychosis, delirium, DRESS syndrome, hallucination, increased serum triglycerides, suicidal ideation
There are no contraindications listed in manufacturer's US labeling.
Canadian labeling: Hypersensitivity to perampanel or any component of the formulation.
Concerns related to adverse effects:
• CNS effects: Dizziness, fatigue (including lethargy and weakness), gait disturbances (including abnormal coordination, ataxia, and balance disorder), and somnolence may occur during therapy; patients should be cautioned about performing tasks that require alertness (eg, operating machinery, driving).
• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiseizure drugs, including perampanel. Symptoms may include fever, rash, lymphadenopathy, eosinophilia, and/or facial swelling, in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems. Early symptoms of hypersensitivity reactions (eg, fever, lymphadenopathy) may occur without rash; discontinuation and conversion to alternate therapy may be required.
• Neuropsychiatric disorders: [US Boxed Warning]: Dose-related serious or life-threatening neuropsychiatric events (including aggression, anger, homicidal ideation and threats, hostility, and irritability) have been reported most often occurring in first 6 weeks of therapy in patients with or without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression; monitor patients closely especially during dosage adjustments and when receiving higher doses. Adjust dose or immediately discontinue use if severe or worsening symptoms occur; permanently discontinue for persistent severe or worsening psychiatric symptoms or behaviors. Inform patients and caregivers to contact their healthcare provider immediately if they experience any atypical behavioral and/or mood changes while taking perampanel or after discontinuing perampanel. Concurrent use with alcohol has been associated with significantly worsened mood and increased anger; patients should avoid the use of alcohol during therapy.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Not recommended for use in patients with severe impairment; dosage adjustment recommended for mild to moderate hepatic impairment.
• Renal impairment: Not recommended for use in patients with severe impairment or on hemodialysis; use caution in patients with moderate impairment and consider slower titration.
Special populations:
• Older adult: Use caution in elderly patients due to increased risk of dizziness, gait or coordination disturbances, somnolence, fatigue-related events, and falls; proceed slowly with dosing titration in patients ≥65 years of age.
• Fall risk: Use with extreme caution in patients who are at risk of falls; use has been associated with falls and traumatic injury (including head injuries and bone fracture).
Dosage forms specific issues:
• Lactose: Formulation may contain lactose.
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (≥1 week) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Fycompa: 0.5 mg/mL (340 mL) [contains sodium benzoate]
Tablet, Oral:
Fycompa: 2 mg, 4 mg, 6 mg, 8 mg
Fycompa: 10 mg, 12 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
No
Suspension (Fycompa Oral)
0.5 mg/mL (per mL): $5.59
Tablets (Fycompa Oral)
2 mg (per each): $24.84
4 mg (per each): $49.08
6 mg (per each): $49.08
8 mg (per each): $49.08
10 mg (per each): $49.08
12 mg (per each): $49.08
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Fycompa: 2 mg, 4 mg, 6 mg, 8 mg
Fycompa: 10 mg, 12 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg
C-III
Tablets: Administer at bedtime without regard to food.
Oral suspension: Shake well before every administration. Use a calibrated measuring device to measure dose (a household teaspoon or tablespoon is not an adequate measuring device). Insert the provided adapter firmly into the neck of the bottle prior to use; adapter should remain in place for the duration of use. Insert the dosing syringe into the adapter and withdraw the dose from the inverted bottle. The cap should be replaced after each use; the cap fits properly when the adapter is in place.
Oral: Administer at bedtime. May be administered without regard to meals.
Oral suspension: Shake well before use. Use the provided graduated oral dosing syringe to measure dose (do not use household teaspoon). Insert the provided adapter firmly into the neck of the bottle prior to use; adapter should remain in place for the duration of use. Insert the dosing syringe into the adapter and withdraw the dose from the inverted bottle. The cap should be replaced after each use; the cap fits properly when the adapter is in place.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202834s016,208277s004lbl.pdf#page=24, must be dispensed with this medication.
Partial-onset seizures: Treatment of partial-onset seizures with or without secondarily generalized seizures as adjunct or monotherapy in patients with epilepsy who are ≥4 years of age.
Primary generalized tonic-clonic seizures: Treatment of primary generalized tonic-clonic seizures as adjunct therapy in patients with epilepsy who are ≥12 years of age.
Substrate of CYP1A2 (Minor), CYP2B6 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): Perampanel may increase CNS depressant effects of Alcohol (Ethyl). Alcohol may also worsen the negative behavioral and psychiatric effects of Perampanel. Risk X: Avoid
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: Perampanel may increase CNS depressant effects of CNS Depressants. Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Fosphenytoin: May decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with fosphenytoin. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if fosphenytoin is discontinued. Risk D: Consider Therapy Modification
Hormonal Contraceptives: Perampanel may decrease serum concentration of Hormonal Contraceptives. Management: Patients should use an alternative, nonhormonal-based form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider Therapy Modification
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levonorgestrel (Systemic): Perampanel may decrease serum concentration of Levonorgestrel (Systemic). Management: Patients taking levonorgestrel-containing contraceptives should use an alternative, non-hormonal form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider Therapy Modification
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
OXcarbazepine: Perampanel may increase serum concentration of OXcarbazepine. OXcarbazepine may decrease serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used with oxcarbazepine. Patients receiving this combination should be followed closely for response to perampanel and oxcarbazepine toxicities. Risk D: Consider Therapy Modification
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Phenytoin: May decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with phenytoin. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if phenytoin is discontinued. Risk D: Consider Therapy Modification
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Topiramate: May increase CNS depressant effects of Perampanel. Topiramate may decrease serum concentration of Perampanel. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valproic Acid and Derivatives: May increase CNS depressant effects of Perampanel. Perampanel may decrease serum concentration of Valproic Acid and Derivatives. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Contraceptives containing levonorgestrel may be less effective; additional nonhormonal forms of contraception are recommended during therapy and for 1 month after the last dose of perampanel. Consult drug interactions database for more detailed information related to the use of perampanel and specific contraceptives.
Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient’s reproductive lifespan (ACOG 2020; NICE 2022).
Obtain total and unbound perampanel serum concentrations twice prior to pregnancy while patient has stable seizure control and is on a minimal dose (Arfman 2020).
Perampanel can be detected in the newborn serum following maternal use during pregnancy (Landmark 2021).
Outcome data following maternal use of perampanel during pregnancy are limited (Goubran 2024; Pack 2024; Vajda 2024,). Data are insufficient to evaluate the risk of specific major congenital malformations or the risk of neurodevelopmental outcomes (IQ scores or autism spectrum disorder) in children following in utero exposure to perampanel. Screen for major congenital malformations and monitor fetal growth when antiseizure medications are used during pregnancy. Conduct age-appropriate developmental screening in children who had in utero exposure to antiseizure medications (Pack 2024).
Data related to pharmacokinetic properties of perampanel during pregnancy are limited (Landmark 2021; Vazquez 2021; Yamamoto 2024). Monitor total and unbound perampanel serum concentrations during pregnancy and adjust doses based on concentrations and seizure control (Arfman 2020; Pack 2024). Formulate a plan to return to prepregnancy dose after delivery if antiseizure medications are changed during pregnancy (NICE 2022).
Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).
Data collection to monitor pregnancy outcomes following exposure to antiepileptic drugs is ongoing. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org).
Perampanel is present in breast milk.
Data related to the presence of perampanel in breast milk are available from case reports:
• Data are available from two patients taking perampanel 4 mg once daily in combination with lamotrigine. Doses were administered in the evening and samples were obtained in the morning. Perampanel concentrations on postpartum day 3 were 60 mcg/L (breast milk) and 630 mcg/L (maternal serum) in one patient. On postpartum day 4, perampanel concentrations were lower than the limit of quantification in breast milk (<10 mcg/L) and 440 mcg/L in the maternal serum of the second patient (Kacirova 2024).
• Breast milk was sampled in a patient taking perampanel 8 mg once daily in combination with brivaracetam and lacosamide. Delivery occurred at 39 weeks gestation and the baby was fully breastfed. Perampanel breast milk concentrations were 0.31 micromole/L (108 mcg/L) in the foremilk on postpartum day 5 (9.5 hours after the maternal dose). Foremilk and hindmilk perampanel concentrations were 0.15 micromole/L (52 mcg/L) 5 weeks postpartum (13 hours after the maternal dose). Perampanel was measurable in the serum of the infant at delivery (0.23 micromole/L; 80 mcg/L), 5 days postpartum (0.49 micromole/L; 171 mcg/L) and 5 weeks postpartum (0.23 micromole/L; 80 mcg/L). At 11 weeks postpartum the infant was partially breastfed and serum concentrations of perampanel were below the limit of detection (<0.15 micromole/L; 52 mcg/L). The baby had expected development at 1 year of age, and no reduced wakefulness or feeding problems (Landmark 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Monitor infants exposed to antiseizure medications via breast milk for sedation, signs of poor sucking, proper weight gain, abnormal platelet counts, abnormal liver function and achievement of developmental milestones (Shawahna 2022; Tomson 2022). Measure antiseizure medication serum concentrations in the infant if symptoms of toxicity occur (Tomson 2022).
Formulate a plan to return to prepregnancy doses if the dose perampanel was changed during pregnancy; gradual dose adjustments over the first 21 days postpartum and maternal therapeutic drug monitoring is recommended (Arfman 2020; NICE 2022).
Seizure frequency/duration; suicidality (eg, suicidal thoughts, depression, behavioral changes) during therapy and for at least 1 month after discontinuation; weight
The exact mechanism by which perampanel exerts antiseizure activity is not definitively known; it is a noncompetitive antagonist of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on postsynaptic neurons. Glutamate is a primary excitatory neurotransmitter in the central nervous center causing many neurological disorders from neuronal over excitation.
Note: Pharmacokinetic data are similar in pediatric patients ≥4 years as adults.
Absorption: Rapid and complete; food slows rate of absorption
Protein binding: ~95% to 96%; primarily albumin and alpha1-acid glycoprotein
Metabolism: Extensive via primary oxidation mediated by CYP3A4/5, and to a lesser extent by CYP1A2 and CYP2B6, and sequential glucuronidation
Half-life elimination: ~105 hours
Time to peak: 0.5 to 2.5 hours; delayed ~1 to 3 hours with food
Excretion: Tablet: Feces (48%); urine (22%)
Altered kidney function: Apparent clearance decreased by 27% in patients with mild renal impairment (CrCl 50 to 80 mL/minute), with a corresponding 37% increase in AUC.
Hepatic function impairment: The total (free and protein bound) exposure (AUC0-inf) of perampanel was 50% greater in mild hepatic impairment and more than doubled (2.55-fold) in moderate hepatic impairment. The AUC0-∞ of free perampanel in mild and moderate hepatic impairment was 1.8-fold and 3.3-fold greater, respectively. The half-life was prolonged in mild impairment (306 vs 125 hours) and moderate impairment (295 vs 139 hours).
