Drug Interaction Study of Apixaban With Cyclosporine or Tacrolimus in Transplant Recipients

Inclusion Criteria: * Kidney or lung transplant patients followed as outpatients who are currently stabilized on immunosuppressive therapy with tacrolimus or cyclosporine * Age 18 or older * At least six months after transplantation * Lack of transplant rejection within the last 12 weeks * Creatinine clearance at least above 15ml/min as calculated by Cockroft-Gault formula * Negative urine pregnancy test for female patients of childbearing potential * Consent to the study * Be a nonsmoker for at least approximately 6 months prior to the study * Have a prothrombin time (PT) and activated partial thromboplastin time (PTT) level below the upper limit of normal * Have a hemoglobin level of above at least 80g/L * Be willing to refrain from the use of anticoagulants and antiplatelet medications including aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks prior and during the entire period of study participation * Be willing to avoid drinking grapefruit juice or consuming natural health products for two weeks prior and during the study period * Be willing to avoid alcohol and cannabis for 48 hours before the study and for the entire duration of the study * Be willing to comply with trial restrictions * Be deemed safe to participate by the study physician Exclusion Criteria: * Patients on antiplatelet therapy for any cardiovascular treatment (such as clopidogrel, prasugrel, ticagrelor). Patients on prophylactic aspirin will be eligible otherwise. * Patients not receiving tacrolimus or cyclosporine * A history of an anaphylactic or severe systemic reactions to apixaban * Any form of substance abuse or major untreated psychiatric disorder * Pregnancy or lactation * Tacrolimus or cyclosporine changes within the last two weeks * Receiving concurrent therapy with warfarin, or are taking medications known to be strong inhibitors of both cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) such as azole-antimycotics antifungals (e.g., ketoconazole, voriconazole.) * Has congenitial or acquired coagulation disorders * Has moderate or severe hepatic disease or other clinically relevant bleeding risk * Use of any drugs or products which at the discretion of the investigator would increase bleeding risk * Has any unstable medical condition that could interfere with the study * Is considered inappropriate for participation by the investigator for any reason * Clinically significant active bleeding, including gastrointestinal bleeding * Lesions or conditions at increased risk of clinically significant bleeding, e.g., recent cerebral infarction (ischemic or hemorrhagic), active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis * Patients who donate blood within 56 days of participating in the study