Drug-Drug Interaction Study of Apixaban with Cyclosporine and Tacrolimus in Healthy Volunteers.
Bashir, B., et al. (2018).Clinical and translational science 11(6): 590-596.
Aims
This study aimed to examine the drug interactions between cyclosporine and tacrolimus (inhibitors of CYP3A4, P-gp, and BCRP) with apixaban.
Interventions
Patients were randomized to sequence A or B. Patients randomized to sequence A received apixaban alone in period I. The subjects then received cyclosporine 100 mg once daily for 3 days followed by another dose of apixaban in period II. In period III, subjects received 5 mg tacrolimus once daily followed by 10 mg apixaban. Whereas those randomized to sequence B received tacrolimus 5 mg once daily for 3 days followed by apixaban in period I. In treatment period II, subjects received 10 mg apixaban alone. The subjects then received cyclosporine 100 mg once daily for 3 days followed by apixaban.
Participants
12 healthy male volunteers were included in this study (non-smoking, aged 18–55 years with a body mass index of 19–33 kg/m2).
Outcomes
Outcomes assessed includeed plasma concentrationâ€time profiles and pharmacokinetic parameters of apixaban (APX) with and without cyclosporine (CsA).
Follow-up
3 days
CET Conclusions
The study tested whether cyclosporine and tacrolimus would alter apixaban exposure. The phase I, open-label, cross-over randomised controlled trial randomly allocated 12 healthy, male volunteers to one of two treatment sequences. The sample size was calculated showing that 12 participants would provide 98% power based on previously reported drug to drug interactions. Administration of of apixaban with cyclosporine or tacrolimus resulted in small changes in apixaban PK parameters that are not clinically meaningful. The authors conclude that they would expect a similar exposure profile in solid organ transplant recipients and that no dose adjustments are needed for transplant patients on cyclosporine or tacrolimus.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT03083782