Drug products: Daxas, Roflumilast 2care4, Roflumilast Accord
ATC code: R03DX07
The exposure of roflumilast is higher in persons of Black or Hispanic origin, women, non-smokers, and persons over 60 years of age. Individually, any of these characteristics does not warrant dose adjustment but in combination, the risk of dose dependent adverse events increases, and dose adjustment may be needed.
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).
Date of litterature search: 2019-05-29
Reviewed by: Karin Schenck-Gustafsson
Approved by: Karin Schenck-Gustafsson