Drug products: Fycompa
ATC code: N03AX22
Substances: perampanel, perampanel hydrate
The relationship between concentration and effect is equivalent in men and women. Women have been found to have a higher occurrence of the adverse events dizziness and headache.
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 .
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 . 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 . 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 . Perampanel dosing should be based on efficacy and tolerability.
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 . The differences for 4 and 12 mg were not significantly better in women . In pharmacokinetic/pharmacodynamic estimations in the population, i.e. studies of concentration-effect relationships, sex was not found to affect the outcome .
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 . Women also had a slightly higher discontinuation rate in the phase III studies than men, 11% and 7%, respectively .
Perampanel lowers progesteron levels why an interaction with contraceptives lowering the anticonceptual effect cannot be excluded . 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).
Date of litterature search: 2018-03-27
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson