Perampanel

Structural formula
General
Non-proprietary name	Perampanel
other names	5 ′ - (2-Cyanophenyl) -1′-phenyl-2,3′-bipyridinyl-6 ′ (1 ′ H ) -one E-2007
Molecular formula	C 23 H 15 N 3 O
External identifiers / databases
CAS number 380917-97-5 EC number 691-969-4 ECHA InfoCard 100.219.846 PubChem 9924495 ChemSpider 8100130 DrugBank DB08883 Wikidata Q868658
Drug information
ATC code	N03 AX22
properties
Molar mass	349.38 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS hazard labeling no classification available
Toxicological data	300 mg kg −1 ( LD 50 ,  mouse ,  oral ) 3200 mg kg −1 ( LD 50 ,  rabbit ,  oral ) 980 mg kg −1 ( LD 50 ,  rat ,  oral ) Draize test , rabbit eye : 100 mg / 24H moderate
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Perampanel ( INN , trade name Fycompa ) is an active ingredient for the treatment of epilepsy ( anticonvulsant ) and as such is approved for the additional therapy of partial seizures with or without secondary generalization in epilepsy patients from the age of twelve. It was approved by the EU Commission in July 2012. Perampanel is subject to prescription .

Mechanism of action

Perampanel is a selective, non-competitive antagonist at AMPA receptors and leads to a targeted blockade of these receptors on nerve cells: AMPA receptors mediate the effect of the exciting messenger substance glutamate . Since there is a disproportion between excitatory and inhibitory signals (in favor of excitation) in epileptic seizures, the aim is to suppress the epileptic seizures and / or their spread in the brain by blocking the AMPA receptors. Perampanel is the first approved active ingredient that specifically attacks AMPA receptors.

Effectiveness and tolerance in clinical studies

In the course of clinical studies that examined the efficacy and tolerability of perampanel in doses of up to 12 mg, a (statistically verified) reduction in the frequency of epileptic seizures was observed from a dose of 4 mg. This was compared with study participants who received a dummy drug without an active ingredient ( placebo ). The most common side effects observed in the studies were dizziness and drowsiness (each affecting more than 10% of the study participants). Other side effects occurred with lower frequencies. The prerequisite for participation in these studies was the occurrence of partial seizures with or without secondary generalization despite current treatment with up to three (other) anticonvulsants.

A rare but forensically important side effect are “aggression and hostile behavior”, which in individual cases can lead to “attacks against other people”.

application

Perampanel is approved up to a maximum dose of 12 mg. The dosage to the individual optimum of efficacy and tolerability takes place in dose steps of 2 mg (depending on additional medication at weekly or bi-weekly intervals). The tablet is taken once a day at bedtime.

Early benefit assessment (AMNOG)

Since 2011, newly approved drugs with new active ingredients in Germany have had to undergo an " early benefit assessment " by the Federal Joint Committee (G-BA) based on Section 35a SGB ​​V ( AMNOG ) if the pharmaceutical manufacturer wants to achieve a higher sales price than just the fixed amount . Only if there is an additional benefit can the drug manufacturer negotiate a higher price than a fixed amount with the umbrella association of statutory health insurance funds (GKV Spitzenverband) . This also applies to perampanel. The Institute for Quality and Efficiency in Health Care (IQWiG) checked in 2012 - on behalf of the G-BA - in accordance with AMNOG whether perampanel offers an additional benefit compared to the previous standard therapy. Such an additional benefit for the IQWiG could not be derived from the dossier because the manufacturer did not present any relevant data for the comparison with the active substances lamotrigine or topiramate . In a statement, the German Society for Epileptology and the German Society for Neurology do not consider the required comparison method to be useful. Based on the IQWiG assessment, the G-BA decided on March 7, 2013 that an additional benefit in relation to the ACT was not proven.

As a result, Eisai decided in June 2013 to no longer offer the drug in Germany for reasons of economy. The care of epilepsy patients who were previously treated with perampanel was still ensured - by the company - despite this withdrawal.

In a second assessment by the IQWiG, no additional benefit was attested either, whereupon Eisai criticized the IQWiG. With the decision of the G-BA of November 6, 2014, the information on perampanel in the version of the decision of March 7, 2013 BAnz AT March 26 , 2013 B4 was repealed. But the G-BA's (new) assessment remained that there was still no additional benefit. Eisai has also confirmed that patient care for the - previously hired - patients is secured. Patients were offered a single import from Switzerland, which Clinigen Group PLC handled. It was criticized that this is a complex and initially controversial procedure for pharmacies.

The procedure was discontinued in April 2016. This means that the drug, which is approved throughout Europe, could only be obtained via a single import (according to Section 73 (3) No. 1 AMG ). This option only exists if the drug is approved in Germany or another EU country, but is not available. Reasons for unavailability can be a market withdrawal or a delivery bottleneck . Eisai continued to complain that the G-BA had not recognized the additional benefit for methodological reasons only and had “failed to adequately assess proven clinical patient benefit”. So that patients did not have to pay for the medication privately, an application could be made to the health insurance company to cover the costs.

Since December 1, 2017, Fycompa has been available on the German market by prescription, because the manufacturer Eisai and the National Association of Statutory Health Insurance Funds have agreed on a reimbursement price.

Web links

• Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Perampanel

Individual evidence

1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
2. ↑ ^{a b c d} Clearsynth: E-2007 ( Memento from April 7, 2014 in the Internet Archive ) (PDF; 579 kB)
3. ↑ European Medicines Agency - EPAR summary for the public (Perampanel) (PDF; 124 kB).
4. ^ JA French, GL Krauss, V. Biton, D. Squillacote, H. Yang, A. Laurenza, D. Kumar, MA Rogawski: Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. In: Neurology. Volume 79, No. 6, Aug 7, 2012, pp. 589-596.
5. ↑ JA French, GL Krauss, BJ Steinhoff, D. Squillacote, H. Yang, D. Kumar, A. Laurenza: Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. In: Epilepsia. 20 Aug 2012. doi: 10.1111 / j.1528-1167.2012.03638.x .
6. ↑ GL Krauss, JM Serratosa, V. Villanueva, M. Endziniene, Z. Hong, J. French, H. Yang, D. Squillacote, HB Edwards, J. Zhu, A. Laurenza: Randomized phase III study 306: adjunctive perampanel for refractory partial onset seizures. In: Neurology. Volume 78, No. 18, May 1, 2012, pp. 1408-1415.
7. ↑ A woman is given a drug that makes her aggressive. ORF , November 27, 2017, accessed on November 27, 2017 . 
8. ↑ Perampanel in epilepsy: no proof of added benefit. IQWiG press release from December 17, 2012.
9. ↑ Statement on Perampanel April 2013 .
10. ↑ Basic reasons for the decision of the Federal Joint Committee on an amendment to the Drugs Directive (AM-RL): Annex XII - Resolutions on the benefit assessment of drugs with new active ingredients according to § 35a SGB V - Perampanel (PDF; 87 kB). Federal Joint Committee , March 7, 2013.
11. ↑ Eisai stops marketing Fycompa. Report in the Ärzte Zeitung from June 26, 2013.
12. ↑ Patient care secured despite the company's withdrawal. Press release Federal Joint Committee , June 25, 2013.
13. ↑ Perampanel in epilepsy: Still no proof of added benefit. Institute for Quality and Efficiency in Health Care (IQWiG) , August 15, 2014, accessed on December 9, 2014 . 
14. ↑ Kirsten Sucker-Sket: Second attempt for Fycompa®: IQWiG still sees no additional benefit. daz.online, August 18, 2014, accessed December 9, 2014 . 
15. ↑ Resolution of the Federal Joint Committee on an amendment to the Drugs Directive (AM-RL): Annex XII - Resolutions on the benefit assessment of drugs with new active ingredients according to § 35a SGB V - Perampanel. (PDF) Federal Joint Committee, November 6, 2014, accessed on December 9, 2014 . 
16. ↑ Eisai wants to continue single imports. Doctors newspaper, December 12, 2014, accessed January 31, 2015 . 
17. ↑ ^{a b c d} Kirsten Sucker-Sket: Perempanel: Free import program for Fycompa expires. daz.online, November 11, 2015, accessed June 10, 2016 . 
18. ↑ Julia Borsch: Fycompa returns . In: DAZ.online . November 28, 2017 ( deutsche-apotheker-zeitung.de [accessed on August 8, 2018]).

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !