Perampanel

• 5'- (2- cyanophenyl ) -1'- phenyl-2, 3 ' - bipyridinyl - 6' ( 1'H )-one
• E- 2007

N03AX22

• 300 mg · kg -1 ( LD50, mouse, oral)
• 3200 mg · kg -1 ( LD50, rabbit, oral)
• 980 mg · kg -1 ( LD50, rat, oral)
• Draize test, rabbit eye: 100 mg/24H Moderate

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Perampanel is a drug used to treat epilepsy ( anticonvulsant ) and as such for the adjunctive treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy admitted from the age of twelve. The approval by the EU Commission in July, 2012. Perampanel (trade name Fycompa ®) subject to medical prescription.

Mechanism of Action

Perampanel is a selective, non- competitive antagonist of AMPA receptors and leads to a specific blockade of these receptors on nerve cells: AMPA receptors mediate this effect of excitatory neurotransmitter glutamate. As an epileptic seizure events a mismatch between excitatory and inhibitory signals is (in favor of excitation), a suppression of epileptic seizures and their propagation in the brain will be pursued through the blockade of AMPA receptors. Perampanel is the first approved drug that specifically acts on AMPA receptors.

Efficacy and tolerability in clinical trials

In clinical studies that investigated the efficacy and tolerability of perampanel at doses up to 12 mg, a ( statistically significant ) reduction in the frequency of epileptic seizures from a dose of 4 mg was observed. Compared this was with study participants who received a placebo with no active substance ( placebo). The observed in the studies on the most common side effects were dizziness and somnolence (if more than 10% of study participants ). Other side effects occurred with lower frequencies. Prerequisite for participation in these studies was the incidence of partial seizures with or without secondary generalization despite current treatment with up to three ( other ) anticonvulsants.

Application

Perampanel is allowed up to a maximum dose of 12 mg. The titration for individual optimum of safety and efficacy carried out in dose increments of 2 mg (depending on additional medication at weekly or biweekly intervals ). The tablet is taken once a day at bedtime.

Early benefit assessment ( AMNOG )

The Institute for Quality and Efficiency in Health Care ( IQWiG) in 2012 at an early benefit assessment pursuant Pharmaceutical Market Restructuring Act ( AMNOG ) checks whether perampanel compared with the previous standard therapy offers an additional benefit. However, for the dossier to such additional benefits can not be derived, since the manufacturer is not provided relevant data for comparison with the active ingredients lamotrigine or topiramate. In a statement, the German Society for Epileptology and the German Society of Neurology, however, do not hold the required comparison methodology would be useful. Dossier evaluation was part of the overall process for early benefit assessment, which was conducted by the Federal Joint Committee (G -BA). The G -BA has decided on March 7, 2013, that an additional benefit in relation to the appropriate comparator therapy was not used.

Then Eisai has decided in June 2013 not to offer the drug in Germany. The supply of epilepsy patients with perampanel is however ensured despite the temporary withdrawal of the company.