Upadacitinib is a novel selective oral Janus kinase 1 (JAK) inhibitor being 
developed for treatment of several inflammatory diseases. Oral contraceptives 
are anticipated to be a common concomitant medication in the target patient 
populations. This study was designed to evaluate the effect of multiple doses of 
upadacitinib on the pharmacokinetics of ethinylestradiol and levonorgestrel in 
healthy female subjects. This phase I, single-center, open-label, 2-period 
crossover study evaluated the effect of multiple doses of 30 mg once daily 
extended-release upadacitinib on the pharmacokinetics of a single oral dose of 
ethinylestradiol/levonorgestrel (0.03/0.15 mg; administered alone in period 1 
and on day 12 of a 14-day regimen of upadacitinib in period 2) in 22 healthy 
female subjects. The ratios (90% confidence intervals) for maximum plasma 
concentration and area under the plasma drug concentration-time curve from time 
zero to infinity following administration of ethinylestradiol/levonorgestrel 
with upadacitinib compared with administration of ethinylestradiol/ 
levonorgestrel alone were 0.96 (0.89-1.02) and 1.1 (1.04-1.19), respectively, 
for ethinylestradiol, and 0.96 (0.87-1.06) and 0.96 (0.85-1.07), respectively, 
for levonorgestrel. The harmonic mean terminal half-life for ethinylestradiol 
(7.7 vs 7.0 hours) and levonorgestrel (37.1 vs 33.1 hours) was similar in the 
presence and absence of upadacitinib. Ethinylestradiol and levonorgestrel were 
bioequivalent in the presence and absence of upadacitinib. Therefore, 
upadacitinib can be administered concomitantly with oral contraceptives 
containing ethinylestradiol or levonorgestrel.