Preparat: Daxas, Roflumilast Accord
ATC kod: R03DX07
Roflumilastexponering är högre hos kvinnor, icke-rökare, personer över 60 års ålder och hos svarta. En kombination av dessa faktorer ökar risken för dosberoende biverkningar och dosjustering kan då bli aktuellt.
Roflumilast is indicated as an add-on in severe chronic obstructive pulmonary disease (COPD) associated with bronchitis in adults [1, 2].
In a small pharmacokinetic study of single and multiple dose roflumilast (6 men, 6 women) no significant sex differences were observed in the pharmacokinetic parameters of roflumilast and roflumilast N-oxide . However, a large pooled analysis of 21 phase I studies of population pharmacokinetic modelling of roflumilast found the covariates patient's sex, smoking and race to influence clearance; of roflumilast and roflumilast N-oxide . Total PDE4 inhibitory activity (tPDE4i) was found to be higher in women, patients with COPD, Black or Hispanic subjects, non-smokers, and in those over 60 years of age . The pharmaceutical company reports a 39% increase in roflumilast AUC and a 33% increase in roflumilast N-oxide AUC in healthy women as compared to men . However, they do not recommend dose adjustment based on patient’s sex unless tolerability problems [1,2]. In patients having a combination of several of the factors described above (for example being a Black or Hispanic, non-smoking woman) dose adjustment may be necessary .
In two randomized controlled clinical trials of roflumilast or placebo in addition to salmeterol or tiotropium, respectively in moderate-to-severe COPD (1147 men, 529 women) found that roflumilast improved mean prebronchodilator FEV1 also when the results were corrected for different characteristics including patient’s sex .
In patients having a combination of several factors yielding a lower clearance (Black or Hispanic origin, female, non-smoker, over 60 years of age) the risk of side effects such as diarrhoea, nausea, or headache and dose adjustment may thus be necessary [2, 4].
It is recommended that women of child bearing potential use effective contraception during use of roflumilast . Regarding teratogenic birth defects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Fler kvinnor än män hämtade ut läkemedel innehållande roflumilast (ATC-kod R03DX07) på recept i Sverige år 2018, 1054 kvinnor och 800 män .
Faktagranskat av: Karin Schenck-Gustafsson
Godkänt av: Karin Schenck-Gustafsson