Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Perampanel

Klassificering: A

Preparat: Fycompa

ATC kod: N03AX22

Substanser: perampanel, perampanelhydrat (4:3)

Sammanfattning

Effekt är visad hos både kvinnor och män och förhållandet mellan koncentration och effekt är likvärdigt. Biverkningarna yrsel och huvudvärk rapporteras oftare hos kvinnor.

Additional information

Data from three randomized, double blind, placebo controlled, multicenter, parallel group, phase III trials of perampanel as add-on antiepileptic treatment in patients >12 years of age with simple or complex epileptic seizures with focal onset (including in total 719 men, 759 women) [1-3] have been analyzed retrospectively from a sex perspective and results are described below [4].

Pharmacokinetics and dosing

The sex divided analysis shows that apparent clearance is 17% lower for women than for men not receiving concomitant enzyme inducing antiepileptic drugs (0.605 L/h compared to 0.730 L/h) and somewhat lower even in women on enzyme inducers [4]. In the patients included in the analysis, the mean weights were 64.9 kg for women and 75.4 kg for men. Doses were not weight-adjusted. No studies of sex differentiated doses have been performed but on group level women have been shown to have better effect given the same doses as men [4]. In contrast to this, an observational pharmacokinetic study in a routine laboratory (41 men (68 samples), 66 women (92 samples)) found a linear dose-concentration relation and no differences between men and women at steady state [5]. Perampanel dosing should be based on efficacy and tolerability.

Effects

In analysis of data from the three randomized, double blind, placebo controlled, multicenter, parallel group, phase III trials of perampanel as add-on antiepileptic treatment in patients >12 years of age with simple or complex epileptic seizures with focal onset (in total 719 men, 759 women) [1-3] both men and women were found to have a reduced seizure frequency. However, women had a better response rate after 28 days for the daily 8 mg perampanel dose [4]. The differences for 4 and 12 mg were not significantly better in women [4]. In pharmacokinetic/pharmacodynamic estimations in the population, i.e. studies of concentration-effect relationships, sex was not found to affect the outcome [6].

Adverse effects

Men and women have been shown to have similar risk of adverse events except for dizziness and headache which were found to be more common among women [4]. Women also had a slightly higher discontinuation rate in the phase III studies than men, 11% and 7%, respectively [4].

Reproductive health issues

Perampanel lowers progesteron levels why an interaction with contraceptives lowering the anticonceptual effect cannot be excluded [7]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Ungefär lika många kvinnor som män hämtade ut tabletter innehållande perampanel (ATC-kod N03AX22) på recept i Sverige år 2017, totalt 253 kvinnor och 267 män [8].

Uppdaterat: 2018-05-16

Litteratursökningsdatum: 2018-03-27

Referenser

  1. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012;79:589-96. PubMed
  2. French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia. 2013;54:117-25. PubMed
  3. Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. 2012;78:1408-15. PubMed
  4. Vazquez B, Yang H, Williams B, Zhou S, Laurenza A. Perampanel efficacy and safety by gender: Subanalysis of phase III randomized clinical studies in subjects with partial seizures. Epilepsia. 2015;-:-. PubMed
  5. Patsalos PN, Gougoulaki M, Sander JW. Perampanel Serum Concentrations in Adults With Epilepsy: Effect of Dose, Age, Sex, and Concomitant Anti-Epileptic Drugs. Ther Drug Monit. 2016;38(3):358-64. PubMed
  6. Gidal BE, Ferry J, Majid O, Hussein Z. Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures. Epilepsia. 2013;54:1490-7. PubMed
  7. Reimers A. New antiepileptic drugs and women. Seizure. 2014;23:585-91. PubMed
  8. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-04-17.] länk

Författare: Mia von Euler

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson