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. |
| 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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FYCOMPA (FYCOMPA).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Caution advised due to potential for infant sedation and poor feeding. Consider alternative agents or discontinue breastfeeding. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["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"] |
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| 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. |