FYCOMPA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FYCOMPA (FYCOMPA).
Non-competitive AMPA receptor antagonist; inhibits glutamate-mediated excitatory neurotransmission by selectively targeting AMPA receptors.
| Metabolism | Hepatic metabolism primarily via CYP3A4; also involves CYP3A5 and CYP2C19. Undergoes extensive oxidative metabolism followed by glucuronidation. |
| Excretion | Renal: approximately 30% as unchanged drug; fecal: approximately 70% (mostly as metabolites, minimal unchanged). |
| Half-life | Terminal elimination half-life is approximately 105 hours (range 80-120 hours) in patients with epilepsy; supports once-daily dosing. |
| Protein binding | ~95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.1 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (well absorbed, minimal first-pass metabolism). |
| Onset of Action | Not applicable; Fycompa (perampanel) is administered orally for chronic treatment; no immediate clinical effect. |
| Duration of Action | Sustained over 24 hours due to long half-life; therapeutic effect develops over weeks with steady-state achieved after ~2-3 weeks. |
| Molecular Weight | 349.38 |
| Action Class | AMPA glutamate receptor antagonist |
| Brand Substitutes | Perampil 2mg Tablet, Hetram 2mg Tablet, Percompa 2mg Tablet, Perampa 2mg Tablet, Ampanel 2 Tablet, Perampil 4mg Tablet, Hetram 4mg Tablet, Percompa 4mg Tablet, Ampanel 4 Tablet, Addperam 4mg Tablet, Perampa 6mg Tablet, Percompa 6mg Tablet, Perampil 6mg Tablet, Ampanel 6 Tablet, Torpanel 6 Tablet |
Initial: 2 mg orally once daily; titrate weekly by 2 mg increments to maintenance dose of 4-12 mg once daily depending on seizure type and tolerability; maximum 12 mg once daily.
| Dosage form | SUSPENSION |
| Renal impairment | CRCL 30-79 mL/min: Max dose 6 mg once daily. CRCL <30 mL/min or ESRD on dialysis: Not recommended. |
| Liver impairment | Child-Pugh A: Max 6 mg once daily. Child-Pugh B: Max 4 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Age 4-17 years: Weight-based: 2 mg once daily initially (using 2 mg tablet); titrate per body weight. <30 kg: max 6 mg once daily; 30-50 kg: max 8 mg once daily; >50 kg: max 12 mg once daily. |
| Geriatric use | Initial dose 2 mg once daily; titrate slowly considering renal function; max 6 mg once daily if CRCL 30-79 mL/min. |
| 1st trimester | Increased risk of major congenital malformations, particularly neural tube defects and cardiac anomalies, based on animal studies and limited human data. Use only if benefit outweighs risk. |
| 2nd trimester | Potential adverse effects on fetal growth and development. Monitor fetal growth via ultrasound. Use only if clearly needed. |
| 3rd trimester | Risk of persistent pulmonary hypertension of the newborn (PPHN) and withdrawal symptoms in neonates. Avoid in late pregnancy unless essential. |
Clinical note
Comprehensive clinical and safety monograph for FYCOMPA (FYCOMPA).
| Placental transfer | Perampanel crosses the placenta in animal studies; human data limited but likely significant due to low molecular weight and lipophilicity. |
| Breastfeeding | Perampanel is excreted in human milk. Infants exposed may experience sedation and difficulty feeding. Monitor for adverse effects. Caution is advised; consider alternative treatments. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Severe hepatic impairment (Child-Pugh C)History of hypersensitivity to perampanel or any excipients
| Precautions | Serious psychiatric and behavioral reactions including hostility, aggression, anger, and homicidal ideation, Suicidal behavior and ideation, Dizziness, gait disturbance, somnolence, and fatigue, Risk of abuse and dependence (Schedule III controlled substance), Withdrawal seizures with abrupt discontinuation |
| Food/Dietary | Take with or without food. Grapefruit or grapefruit juice may decrease perampanel levels; avoid concurrent use. No other significant food interactions reported. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Fycompa (perampanel) is Pregnancy Category C. First trimester: May cause fetal harm based on animal studies showing developmental toxicity (reduced fetal weight, increased skeletal variations) at clinically relevant doses. Second/third trimester: Limited human data; risk of neural tube defects, cardiac anomalies, and neurobehavioral effects in animal models. Newborn may experience withdrawal symptoms or sedation if exposed in utero near term. |
| Fetal Monitoring | Monitor pregnancy status with reliable contraception; perform fetal ultrasound for structural anomalies. If exposed, monitor infant for sedation, poor feeding, and growth. Consider therapeutic drug monitoring during pregnancy due to altered pharmacokinetics. |
| Fertility Effects | Potential for reduced fertility in males and females based on animal studies (decreased sperm count, estrous cycle irregularities). Human data limited. |
| Clinical Pearls |
| FYCOMPA (perampanel) is a selective non-competitive AMPA receptor antagonist. Titrate slowly: start 2 mg/day, increase by 2 mg/day every 1-2 weeks, max 12 mg/day. Renal impairment (CrCl <30 mL/min): max 6 mg/day. Hepatic impairment: reduce dose. Monitor for serious psychiatric and behavioral reactions (aggression, hostility, irritability, agitation, suicidal ideation). Can cause somnolence, dizziness, and gait disturbance; patients should not drive or operate machinery. Abrupt discontinuation may precipitate withdrawal seizures; taper gradually. Consider drug interactions: carbamazepine increases clearance, oxcarbazepine reduces levels, and alcohol exacerbates CNS depression. |
| Patient Advice | Take FYCOMPA exactly as prescribed; do not stop suddenly or change dose without consulting your doctor. · Avoid alcohol and CNS depressants (benzodiazepines, narcotics) as they may increase drowsiness and dizziness. · Do not drive, operate heavy machinery, or engage in hazardous activities until you know how the medication affects you. · Report any mood changes, unusual behavior, aggression, hostility, or thoughts of self-harm immediately to your healthcare provider. · If you are pregnant or planning to become pregnant, discuss the risks with your doctor; FYCOMPA may harm the fetus. · Store at room temperature, away from moisture and heat, out of reach of children. |