Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy

References

• Rana A, Gruessner A, Agopian VG, et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015;150(3):252–259.
   PubMed Web of Science ®Google Scholar
• Costanzo MR, Dipchand A, Starling R, et al. The international society of heart and lung transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914–956.
   PubMed Web of Science ®Google Scholar
• Kidney Disease: Improving Global Outcomes Transplant Work G. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl 3):S1–155.
   PubMedGoogle Scholar
• Lucey MR, Terrault N, Ojo L, et al. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the study of liver diseases and the american society of transplantation. Liver Transpl. 2013;19(1):3–26.
   PubMed Web of Science ®Google Scholar
• Saez-Gimenez B, Berastegui C, Loor K, et al. Deep vein thrombosis and pulmonary embolism after solid organ transplantation: an unresolved problem. Transplant Rev (Orlando). 2015;29(2):85–92.
   PubMedGoogle Scholar
• Irish A. Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention. Am J Cardiovasc Drugs. 2004;4(3):139–149.
   PubMedGoogle Scholar
• Vanrenterghem Y, Roels L, Lerut T, et al. Thromboembolic complications and haemostatic changes in cyclosporin-treated cadaveric kidney allograft recipients. Lancet. 1985;1(8436):999–1002.
   PubMed Web of Science ®Google Scholar
• Gruber SA, Chavers B, Payne WD, et al. Allograft renal vascular thrombosis–lack of increase with cyclosporine immunosuppression. Transplantation. 1989;47(3):475–478.
   PubMed Web of Science ®Google Scholar
• Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14.
   PubMed Web of Science ®Google Scholar
• 2016 Annual Data Report. Scientific registry of transplant recipients. [ cited 2018 July 6] Available from: http://srtr.transplant.hrsa.gov/annual_reports/Default.aspx
   Google Scholar
• Prograf (Tacrolimus) [Package Insert]. Northbrook, IL: Astellas Pharma US, Inc.
   Google Scholar
• Christians U, Jacobsen W, Benet LZ, et al. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clin Pharmacokinet. 2002;41(11):813–851.
   PubMed Web of Science ®Google Scholar
• Huang F, Voelk C, Trampisch M, et al. Pharmacokinetic interaction between faldaprevir and cyclosporine or tacrolimus in healthy volunteers: a prospective, open-label, fixed-sequence, crossover study. Basic Clin Pharmacol Toxicol. 2018;123(1):84–93.
   PubMed Web of Science ®Google Scholar
• Lemahieu WP, Hermann M, Asberg A, et al. Combined therapy with atorvastatin and calcineurin inhibitors: no interactions with tacrolimus. Am J Transplant. 2005;5(9):2236–2243.
   PubMed Web of Science ®Google Scholar
• Hebert MF. Contributions of hepatic and intestinal metabolism and P-glycoprotein to cyclosporine and tacrolimus oral drug delivery. Adv Drug Deliv Rev. 1997;27(2–3):201–214.
   PubMed Web of Science ®Google Scholar
• Sandimmune (Cyclosporine, USP) [Package Insert]. Novartis Pharmaceuticals Corporation, East Hanover, NJ. (2015).
   Google Scholar
• Neoral (Cyclsoporine, USP [MODIFIED]) [Package Insert]. Novartis Pharmaceuticals Corporation, East Hanover, NJ. (2015).
   Google Scholar
• Chou CL, Chou CY, Huang YY, et al. Prescription trends of immunosuppressive drugs in post-heart transplant recipients in Taiwan, 2000–2009. Pharmacoepidemiol Drug Saf. 2014;23(12):1312–1319.
   PubMed Web of Science ®Google Scholar
• Huang YY, Hsu CC, Chou CL, et al. Trends in the use of maintenance immunosuppressive drugs among liver transplant recipients in Taiwan: a nationwide population-based study. Pharmacoepidemiol Drug Saf. 2016;25(6):661–667.
   PubMed Web of Science ®Google Scholar
• Paimela H. Persistence of gastric hypoacidity in uraemic patients after renal transplantation. Scand J Gastroenterol. 1985;20(7):873–876.
   PubMed Web of Science ®Google Scholar
• Sodhi SS, Guo JP, Maurer AH, et al. Gastroparesis after combined heart and lung transplantation. J Clin Gastroenterol. 2002;34(1):34–39.
   PubMed Web of Science ®Google Scholar
• Bodet-Milin C, Querellou S, Oudoux A, et al. Delayed gastric emptying scintigraphy in cystic fibrosis patients before and after lung transplantation. J Heart Lung Transplant. 2006;25(9):1077–1083.
   PubMed Web of Science ®Google Scholar
• Ozkaya O, Derici U, Buyan N, et al. Gastric emptying time in renal transplant recipients treated with cyclosporine. Transplant Proc. 2003;35(8):2927–2930.
   PubMed Web of Science ®Google Scholar
• Kochhar G, Parungao JM, Hanouneh IA, et al. Biliary complications following liver transplantation. World J Gastroenterol. 2013;19(19):2841–2846.
   PubMed Web of Science ®Google Scholar
• Masuda S, Goto M, Kiuchi T, et al. Enhanced expression of enterocyte P-glycoprotein depresses cyclosporine bioavailability in a recipient of living donor liver transplantation. Liver Transpl. 2003;9(10):1108–1113.
   PubMed Web of Science ®Google Scholar
• Kushihara H, Kuzuya T, Miwa Y, et al. Changes in ABCB1 mRNA expression in peripheral blood cells before and after renal transplantation. Biol Pharm Bull. 2016;39(7):1085–1090.
   PubMed Web of Science ®Google Scholar
• Sugawara Y, Makuuchi M, Kaneko J, et al. Correlation between optimal tacrolimus doses and the graft weight in living donor liver transplantation. Clin Transplant. 2002;16(2):102–106.
   PubMed Web of Science ®Google Scholar
• Baldwin MR, Arcasoy SM, Shah A, et al. Hypoalbuminemia and early mortality after lung transplantation: a cohort study. Am J Transplant. 2012;12(5):1256–1267.
   PubMed Web of Science ®Google Scholar
• Becker BN, Becker YT, Heisey DM, et al. The impact of hypoalbuminemia in kidney-pancreas transplant recipients. Transplantation. 1999;68(1):72–75.
   PubMed Web of Science ®Google Scholar
• Sang BH, Bang JY, Song JG, et al. Hypoalbuminemia within two postoperative days is an independent risk factor for acute kidney injury following living donor liver transplantation: a propensity score analysis of 998 consecutive patients. Crit Care Med. 2015;43(12):2552–2561.
   PubMed Web of Science ®Google Scholar
• Haroldson JA, Kramer LE, Wolff DL, et al. Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia. Ann Pharmacother. 2000;34(2):183–187.
   PubMed Web of Science ®Google Scholar
• Huang ML, Venkataramanan R, Burckart GJ, et al. Drug-binding proteins in liver transplant patients. J Clin Pharmacol. 1988;28(6):505–506.
   PubMedGoogle Scholar
• Haughey DB, Kraft CJ, Matzke GR, et al. Protein binding of disopyramide and elevated alpha-1-acid glycoprotein concentrations in serum obtained from dialysis patients and renal transplant recipients. Am J Nephrol. 1985;5(1):35–39.
   PubMed Web of Science ®Google Scholar
• Burckart GJ, Frye RF, Kelly P, et al. Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation. Clin Pharmacol Ther. 1998;63(3):296–302.
   PubMed Web of Science ®Google Scholar
• Navasa M, Feu F, Garcia-Pagan JC, et al. Hemodynamic and humoral changes after liver transplantation in patients with cirrhosis. Hepatology. 1993;17(3):355–360.
   PubMed Web of Science ®Google Scholar
• Piscaglia F, Zironi G, Gaiani S, et al. Systemic and splanchnic hemodynamic changes after liver transplantation for cirrhosis: a long-term prospective study. Hepatology. 1999;30(1):58–64.
   PubMed Web of Science ®Google Scholar
• Li M, Zhao Y, Humar A, et al. Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans. Expert Opin Drug Metab Toxicol. 2016;12(3):231–243.
   PubMed Web of Science ®Google Scholar
• Shah JN, Haigh WG, Lee SP, et al. Biliary casts after orthotopic liver transplantation: clinical factors, treatment, biochemical analysis. Am J Gastroenterol. 2003;98(8):1861–1867.
   PubMed Web of Science ®Google Scholar
• Broekroelofs J, Navis GJ, Stegeman CA, et al. Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss. Transplantation. 2000;69(8):1624–1628.
   PubMed Web of Science ®Google Scholar
• Lindelow B, Bergh CH, Herlitz H, et al. Predictors and evolution of renal function during 9 years following heart transplantation. J Am Soc Nephrol. 2000;11(5):951–957.
   PubMed Web of Science ®Google Scholar
• Giacomini KM, Huang SM, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215–236.
   PubMed Web of Science ®Google Scholar
• Gertz M, Cartwright CM, Hobbs MJ, et al. Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential. Pharm Res. 2013;30(3):761–780.
   PubMed Web of Science ®Google Scholar
• Lemahieu WP, Maes BD, Verbeke K, et al. CYP3A4 and P-glycoprotein activity in healthy controls and transplant patients on cyclosporin vs. tacrolimus vs. sirolimus. Am J Transplant. 2004;4(9):1514–1522.
   PubMed Web of Science ®Google Scholar
• Lin JH, Chiba M, Baillie TA. Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol Rev. 1999;51(2):135–158.
   PubMed Web of Science ®Google Scholar
• Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–2352.
   PubMed Web of Science ®Google Scholar
• Investigators E, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–2510.
   PubMed Web of Science ®Google Scholar
• Hokusai VTEI, Buller HR, Decousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369(15):1406–1415.
   PubMed Web of Science ®Google Scholar
• Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013;369(9):799–808.
   PubMed Web of Science ®Google Scholar
• Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–295.
   PubMed Web of Science ®Google Scholar
• Troconiz IF, Tillmann C, Liesenfeld KH, et al. Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing primary elective total hip replacement surgery. J Clin Pharmacol. 2007;47(3):371–382.
   PubMed Web of Science ®Google Scholar
• Hodin S, Basset T, Jacqueroux E, et al. In vitro comparison of the role of P-Glycoprotein and breast cancer resistance protein on direct oral anticoagulants disposition. Eur J Drug Metab Pharmacokinet. 2018;43(2):183–191.
   PubMed Web of Science ®Google Scholar
• Hartter S, Sennewald R, Nehmiz G, et al. Oral bioavailability of dabigatran etexilate (Pradaxa((R))) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013;75(4):1053–1062.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Hu ZY. Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate. Br J Pharmacol. 2014;171(4):1043–1053.
   PubMed Web of Science ®Google Scholar
• Kumar P, Gordon LA, Brooks KM, et al. Differential Influence of the antiretroviral pharmacokinetic enhancers ritonavir and cobicistat on intestinal P-glycoprotein transport and the pharmacokinetic/pharmacodynamic disposition of dabigatran. Antimicrob Agents Chemother. 2017;61:11.
   Web of Science ®Google Scholar
• Pradaxa (Dabigatran etexilate mesylate) [Package Insert]. Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT. (2018).
   Google Scholar
• Xarelto (Rivaroxaban) [Package Insert]. Titusville, NJ.: Janssen Pharmaceuticals, Inc.
   Google Scholar
• U.S. Food and Drug Administration. Xarelto (rivaroxaban) Clinical Pharmacology Biopharmaceutics Review. [ cited 2018 July 9] Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022406Orig1s000ClinPharmR.pdf
   Google Scholar
• Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455–466.
   PubMed Web of Science ®Google Scholar
• Grillo JA, Zhao P, Bullock J, et al. Utility of a physiologically-based pharmacokinetic (PBPK) modeling approach to quantitatively predict a complex drug-drug-disease interaction scenario for rivaroxaban during the drug review process: implications for clinical practice. Biopharm Drug Dispos. 2012;33(2):99–110.
   PubMed Web of Science ®Google Scholar
• Savaysa (Edoxaban) [Package Insert]. Daiichi Sankyo, Inc., Basking Ridge, NJ.).
   Google Scholar
• U.S. Food and Drug Administration. Savaysa (edoxaban) clinical pharmacology biopharmaceutics review. [ cited 2018 July 9] Avaliable from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206316Orig1Orig2s000ClinPharmR.pdf
   Google Scholar
• Parasrampuria DA, Mendell J, Shi M, et al. Edoxaban drug-drug interactions with ketoconazole, erythromycin, and cyclosporine. Br J Clin Pharmacol. 2016;82(6):1591–1600.
   PubMed Web of Science ®Google Scholar
• Nyberg J, Karlsson KE, Jonsson S, et al. edoxaban exposure-response analysis and clinical utility index assessment in patients with symptomatic deep-vein thrombosis or pulmonary embolism. CPT Pharmacometrics Syst Pharmacol. 2016;5(4):222–232.
   PubMedGoogle Scholar
• Eliquis (Apixaban) [Package Insert]. Bristol-Myers Squibb Company, Princeton, NJ.).
   Google Scholar
• Byon W, Nepal S, AE S, et al. Regional gastrointestinal absorption of apixaban in healthy subjects. J Clin Pharmacol. 2018;58(7):965–971.
   PubMed Web of Science ®Google Scholar
• Zhang D, He K, Herbst JJ, et al. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013;41(4):827–835.
   PubMed Web of Science ®Google Scholar
• Byon W, Sweeney K, Frost C, et al. Population pharmacokinetics, pharmacodynamics, and exploratory exposure-response analyses of apixaban in subjects treated for venous thromboembolism. CPT Pharmacometrics Syst Pharmacol. 2017;6(5):340–349.
   PubMedGoogle Scholar
• Bashir B, Stickle DF, Chervoneva I, et al. Drug-drug interaction study of apixaban with cyclosporine and tacrolimus in healthy volunteers. Clin Transl Sci. 2018;11:590–596.
   PubMed Web of Science ®Google Scholar
• U.S. Food and Drug Administration. Eliquis (apixaban) clinical pharmacology biopharmaceutics review. [ cited 2018 July 9] Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202155Orig1s000ClinPharmR.pdf
   Google Scholar
• Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349(10):931–940.
   PubMed Web of Science ®Google Scholar
• Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250–1259.
   PubMed Web of Science ®Google Scholar
• Wannhoff A, Weiss KH, Schemmer P, et al. Increased levels of rivaroxaban in patients after liver transplantation treated with cyclosporine A. Transplantation. 2014;98(2):e12–13.
   PubMed Web of Science ®Google Scholar
• Ambrosi P, Kreitmann B, Cohen W, et al. Anticoagulation with a new oral anticoagulant in heart transplant recipients. Int J Cardiol. 2013;168(4):4452–4453.
   PubMed Web of Science ®Google Scholar
• Samuelson BT, Cuker A, Siegal DM, et al. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: a systematic review. Chest. 2017;151(1):127–138.
   PubMed Web of Science ®Google Scholar
• Lichvar AB, Moore CA, Ensor CR, et al. Evaluation of direct oral anticoagulation therapy in heart and lung transplant recipients. Prog Transplant. 2016;26(3):263–269.
   PubMed Web of Science ®Google Scholar
• Groenendaal D, Strabach G, Garcia-Hernandez A, et al. The pharmacokinetics of darexaban are not affected to a clinically relevant degree by rifampicin, a strong inducer of P-glycoprotein and CYP3A4. Br J Clin Pharmacol. 2013;75(2):440–449.
   PubMed Web of Science ®Google Scholar
• Fredenburgh JC, Gross PL, Weitz JI. Emerging anticoagulant strategies. Blood. 2017;129(2):147–154.
   PubMed Web of Science ®Google Scholar