| Identification | Back Directory | [Name]
PeraMpanel | [CAS]
380917-97-5 | [Synonyms]
E 2007
CS-1116
Perampane
PeraMpanel
Pyronoprene
ER 155055-90
PeraMpanel-D5
PERAMPANEL API
PeraMpanel-13C6
Perampanel(E2007)
Perampanel Impurity
Perampanel Impurity 8
ER 155055-90 Perampanel
E 2007; ER 155055-90; E-2007; E2007
2-(2-oxo-1-phenyl-5-pyridin-2-
ylpyridin-3-yl)benzonitrile
Benzonitrile, 2-(1',6'-dihydro-6'-oxo-1'-phenyl[2,3'-bipyrid...
3-(2-Cyanophenyl)-1-phenyl-5-(2-pyridyl)-1,2-dihydropyridin-2-one
3-(2-Cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one
2-(6'-Oxo-1'-phenyl-1',6'-dihydro-[2,3'-bipyridin]-5'-yl)benzonitrile
Benzonitrile, 2-(1',6'-dihydro-6'-oxo-1'-phenyl[2,3'-bipyridin]-5'-yl)-
2-(2-oxo-1-phenyl-5-(pyridin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile
Perampanel/D3-labelled (3R,4R）-1-Benzyl-N,4-dimethylpiperidine-3-amine dihydrochloride
Perampane,Perampanel
Benzonitrile, 2-(1',6'-dihydro-6'-oxo-1'-phenyl[2,3'-bipyridin]-5'-yl) | [EINECS(EC#)]
691-969-4 | [Molecular Formula]
C23H15N3O | [MDL Number]
MFCD19443693 | [MOL File]
380917-97-5.mol | [Molecular Weight]
349.385 |
| Chemical Properties | Back Directory | [Boiling point ]
619.1±55.0 °C(Predicted) | [density ]
1.31±0.1 g/cm3(Predicted) | [solubility ]
Soluble in DMSO | [form ]
Powder | [pka]
4.73±0.19(Predicted) |
| Hazard Information | Back Directory | [Definition]
ChEBI: A member of the class of bipyridines that is 2,3'-bipyridin-6'-one substituted at positions 1' and 5' by phenyl and 2-cyanophenyl groups respectively. Used as an adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy. | [Originator]
Eisai (Japan) | [Uses]
Isotope labelled Perampanel (P285520), is an antiepileptic drug. It inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced increases in intracellular Ca2+ and selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing neuronal excitation. | [Brand name]
Fycompa | [Clinical Use]
Selective AMPA-type glutamate receptor antagonist:
Antiepileptic | [Drug interactions]
Potentially hazardous interactions with other drugs
Antidepressants: anticonvulsant effect antagonised;
avoid with St John’s wort.
Antiepileptics: concentration reduced by
carbamazepine, fosphenytoin, oxcarbazepine and
phenytoin.
Antimalarials: anticonvulsant effect antagonised by
mefloquine.
Antipsychotics: anticonvulsant effect antagonised.
Orlistat: possibly increased risk of convulsions.
Progestogens: high-dose perampanel reduces plasma
concentration of progestogens (possibly reduced
contraceptive effect). | [Metabolism]
Extensively metabolised via primary oxidation via the
cytochrome P450 isoenzyme CYP3A sub family and
sequential glucuronidation.
Perampanel is excreted in the urine and faeces mainly as
oxidative and conjugated metabolites. |
| Questions And Answer | Back Directory | [Description]
Perampanel (licensed in 2012) is a third- generation AED known with the proprietary brand name of Fycompa® (Eisai, Hatfield) in the UK and Banzel® (Eisai, Hatfield) in the USA.
| [Indications]
Epilepsy: Adjunctive treatment of focal seizures with or without secondary generalization and primary generalized tonic- clonic seizures.
| [Dose titration]
Epilepsy— adjunctive therapy: 2 mg nocte for at least 14 days, then increased by 2 mg every 14 or more days; usual maintenance 4– 8 mg nocte (max. 12 mg nocte).
| [Interactions]
With AEDs
- Some AEDs known as CYP450 3A enzyme inducers (carbamazepine, oxcarbazepine, phenytoin) have been shown to increase perampanel clearance and consequently to decrease plasma concentrations of perampanel. Carbamazepine, a known potent enzyme inducer, reduced perampanel levels by two- thirds in a study performed on healthy subjects
- In the epilepsy population pharmacokinetic analysis, perampanel was found to decrease the clearance of oxcarbazepine by 26%. Oxcarbazepine is rapidly metabolized by cytosolic reductase enzyme to the active metabolite, monohydroxycarbazepine. The effect of perampanel on monohydroxycarbazepine concentrations is not known.
With other drugs
- Strong inducers of cytochrome P450, such as rifampicin and St John’s Wort (Hypericum perforatum), are expected to decrease perampanel concentrations.
- In healthy subjects, the CYP3A4 inhibitor ketoconazole increases perampanel exposure.
- Perampanel can make certain hormonal contraceptives such as levonorgestrel less effective.
- Decrease in exposure of midazolam may be caused by perampanel.
With alcohol/food
- Drinking alcohol while taking perampanel can affect a patients’ alertness and ability to drive or use tools or machines. It can also aggravate irritability, confusion, and depression.
- There are no specific foods that must be excluded from diet when taking perampanel.
| [Special populations]
Hepatic impairment
- Increase at intervals of at least 2 weeks, up to a maximum of 8 mg daily, in mild- to- moderate impairment.
- Avoid in severe impairment.
Renal impairment
Avoid in moderate or severe impairment.
Pregnancy
- There are limited amount of data available on the use of perampanel in pregnant women and the potential risk for humans is unknown.
- Perampanel is not recommended in pregnancy and female patients must use a reliable method of contraception to avoid becoming pregnant while being treated with perampanel (this should be continued for 1 month after stopping treatment).
- As perampanel can make certain hormonal contraceptives such as levonorgestrel less effective, other forms of safe and effective contraception (such as a condom or coil) should be used when taking perampanel (this should be continued for 1 month after stopping treatment).
- Perampanel has been found to be present in milk in animal studies and it is recommended that breastfeeding should be avoided.
| [Behavioural and cognitive effects in patients with epilepsy]
For this third- generation agent, clinical experience is still limited, and little is known about its positive and negative psychotropic properties, and their implications for the management of behavioural symptoms in patients with epilepsy. There are initial reports of behavioural disturbances (especially depression, anxiety, irritability, and psychosis), which seem to be dose- related and tend to appear within the first weeks of treatment. Reports of cognitive effects (mainly affecting memory) are relatively rare.
| [Psychiatric use]
Perampanel has no indications for the treatment of psychiatric disorders. There is insufficient experience with perampanel to draw any conclusion regarding its psychotropic profile.
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