EVALUATION OF THE PHARMACOCINETICS OF WARFARIN IN THE TRIANGLE OF FOOD, DRUG AND WARFARIN

Abstract

Well managed and planned warfarin treatment has been an important anticoagulation alternative and guidance of anticoagulant providers has been a promoter for obtaining optimum results. Warfarin is currently one of the most widely used oral anticoagulants despite its complex pharmacokinetic and pharmacodynamic profile. It is clinically difficult to reach optimal anticoagulation with this agent due to its multiple food and medicine interactions. Drug therapy has to be individualized for each patient and the possibility of enhancement, intoxication or decrease in the efficacy of concomitantly used appropriate herbal and other medicines by warfarin must always be kept in mind. Inappropriate control and monitorization of anticoagulation may expose patients to excess or ineffective anticoagulation leading to hemorrhage or thromboembolic complication risks respectively. Especially fluctuations in the ingestion of vitamin K has a significant effect on the degree of anticoagulation in patients receiving varfarin treatment. Additionally, various dietary supplements and recent increase in herbal medicinal products may lead to unwanted results in levels of anticoagulation. The aim of this review is to discuss the effects of most frequently used drugs, food and dietary supplements on the pharmacokinetics of warfarin.

Keywords

• Drug-food interactions
• anticoagülants
• warfarin
• pharmacokinetic
• bioavailability

BESİN, İLAÇ VE VARFARİN ÜÇGENİNDE, VARFARİNİN FARMAKOKİNETİĞİNİN DEĞERLENDİRİLMESİ

Abstract

İyi yönetilen ve planlanan varfarin tedavisi önemli bir antikoagülan seçenek olmuştur ve antikoagülasyon sağlayıcılarının rehberliği optimum sonuçları elde etmeyi kolaylaştırmıştır. Karmaşık farmakokinetik ve farmakodinamik profiline rağmen, varfarin, günümüzde de en yaygın kullanılan oral antikoagülan ajanlardan biridir. Bu ajan ile optimal antikoagülasyona ulaşmak, birçok gıda ve ilaç etkileşimi nedeniyle klinik olarak zordur. İlaç tedavisi her bir hastaya uyacak şekilde özel olarak uyarlanmalı ve uygun şekilde birlikte kullanılabilecek bitkisel ilaçların ve diğer ilaçların etkinliğini artırabileceği veya ilaç toksisitesini azaltabileceği mutlaka göz önünde bulundurulmalıdır. Uygunsuz antikoagülasyon kontrolü, hastaları sırasıyla aşırı ve yetersiz koagülasyon nedeniyle kanama veya tromboembolik komplikasyon riskinde artışa maruz bırakabilmektedir. Özellikle K vitamini alımındaki dalgalanmaların, varfarin ile tedavi edilen hastalarda antikoagülasyon derecesi üzerinde önemli bir etkisi bulunmaktadır. Ek olarak, çeşitli diyet takviyeleri ve bitkisel ürünlerin kullanımındaki artış da antikoagülan seviyelerinde istenmeyen sonuçlara yol açabilmektedir. Bu derlemenin amacı, en sık kullanılan ilaçlar, besin ve diyet takviyelerinin varfarinin farmakokinetiği üzerindeki etkilerini tartışmaktır.

Keywords

• İlaç-besin etkileşimleri
• antikoagülanlar
• varfarin
• farmakokinetik
• biyoyararlanım

References

1. Sawicka-Powierza JJ, Rogowska-Szadkowska D, Oltarzewska AM, Chlabicz S. Factors influencing activity of oral anticoagulants. Interactions with drugs and food. Polski Merkuriusz Lekarski. 2008; 24: 458-462.
2. You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, Fang MC, Hylec EM, Schulman S, Go AS, Hughes M, Spencer FA, Manning WJ, Halperin JL, Lip GY. Antithrombotic therapy for atrial fibrilation: antithrombotic therapy and prevention of thrombosis 9th ed: American collage of chest physicians evidence-based clinical practice guidelines. Chest. 2012; 141: 531-575.
3. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014; 64(21): 2305-7.
4. Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillion E. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Eur J Haematol. 2015; 95(5):389-404. doi: 10.1111/ejh.12610. Epub 2015 Jul 16. Review.
5. Gelosa P, Castiglioni L, Tenconi M, Baldessin L, Racagni G, Corsini A, Bellosta S. Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs). Pharmacol Res. 2018; 135:60-79. doi: 10.1016/j.phrs.2018.07.016. Epub 2018 Jul 21.
6. Selvi M, Önay S, Zencir C, Akgüllü Ç, Güngör H. CHADS2 ve CHA2DS2-VASc Skorları Koroner Arter Bypas Cerrahisi Sonrası Gelişen Atriyal Fibrilasyonunun Öngörücüsü müdür? Koşuyolu Heart Journal 2014; 17(3): 159-162.
7. Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010;376:975–83. DOI: 10.1016/S0140-6736(10)61194-4.
8. De Caterina R, Husted S, Wallentin L, et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease position paper. J Am Coll Cardiol 2012;59:1413–25. DOI: 10.1016/j.jacc.2012.02.008; PMID: 22497820.

9. Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillion E. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. Eur J Haematol. 2015 Nov;95(5):389-404. doi: 10.1111/ejh.12610. Epub 2015 Jul 16. Review.
10. Vranckx P, Valgimigli M, Heidbuchel H. The Significance of Drug–Drug and Drug–Food Interactions of Oral Anticoagulation. Arrhythmia & Electrophysiology Review 2018;7(1):55–61. DOI: 10.15420/aer.2017.50.1.
11. Holford H.D.N. Clinical Pharmacokinetics and Pharmacodynamics of Warfarin Understanding the Dose-Effect Relationship. Clinical Pharmacokinetics II. 1986; 483-504.
12. Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato M, Kitzmiller JP, Pepi M, Tremoli E, Baldassarre D. Old and new oral anticoagulants: Food, herbal medicines and drug interactions. Blood Rev. 2017 Jul;31(4):193-203. doi: 10.1016/j.blre.2017.02.001. Epub 2017 Feb 5. Review.
13. Leite P.M, Martins M.A.P, Castilho R.O. Review on mechanisms and interactions in concomitant use of herbs and warfarin therapy. Biomedicine and Pharmacutheraphy 2016; 83: 14-21.
14. Nutescu E.A, Shapiro N.L, Ibrahim S, West P. Warfarin and its interactions with foods, herbs and other dietary supplements. Expert Opin. Drug Saf. 2006; 5(3):433-451.
15. Poller L. International Normalized Ratios (INR): the first 20 years. J Thromb Haemost 2004;2: 849–60. DOI: 10.1111/j.15387836.2004.00775.x; PMID: 15140114.
16. Borgman M.P, Pendleton R.C, McMillin G.A et al. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation. Thromb Haemost 2012; 108: 561–569.
17. Ertaş F.S. Statins with a persperctive of lifelong therapy. Turk Kardiyol Dern Ars. 2009; 37: 161-167.
18. Bovill E.G., Fung M., Cushman M. Vitamin K and oral anticoagulation: thought for food. Am. J. Med. 2004; 116: 711-713.
19. Weizmann N., Peteson J.W., Haytowitz D. et al. Vitamin K content of fast foods and snack foods in the US diet. J. Food Compos. Anal. 2004; 17: 379-384.
20. Daniel M.W., Clark N.P., Kaatz S., Schnurr T. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J. Thromb. Thrombolysis. 2016; 41: 187-205.
21. Kovacs M.J, Rodger M, Anderson D.R et al. Comparison of 10 mg and 5 mg warfarin initiation nomograms together with low molecular weight heparin for outpatient treatment of acute venous thromboembolism. Ann Intern Med 2003; 138: 714–719
22. Minno A.D., Frigerio B., Spadarelle G., Ravani A., Sansaro D. et al. Old and new oral anticoagülants: Food, herbal medicines and drug interactions. Blood Reviews, 2017; 31: 193-203.
23. Ansell J., Hirsh J., Poller L., Bussey H., Jacobson A., Hylek E. The Pharmacology and management of the vitamin K antagonists: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126: 204-233.
24. Holbrook A.M., Pereira J.A., Labiris R. et al. Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 2005; 165(10): 1095-1106.
25. Wingard L.B., O'Reilly R.A., Levy G., Pharmacokinetics of warfarin enantiomers: a search for intrasubject correlations. Clinical Pharmacology and Therapeutics 1978; 23: 212-217.
26. Stading J.A, Skrabal M.Z, Faulkner M.A. Seven cases of interaction between warfarin and cyclooxygenase-2 inhibitors. Am J Health Syst Pharm. 2001; 58: 2076-2080.
27. Ge B, Zhang Z, Zuo Z. Updates on the clinical evidenced herb-warfarin interactions. Evid Based Complement Alternat Med. 2014;2014:957362. doi: 10.1155/2014/957362. Epub 2014 Mar 18. Review.
28. Turkmenoglu FP, Kutsal YG, Dolgun AB, Diker Y, Baydar T. Evaluation of herbal product use and possible herb-drug interactions in Turkish elderly. Complement Ther Clin Pract. 2016 May;23:46-51. doi: 10.1016/j.ctcp.2016.03.004. Epub 2016 Mar 18.
29. Bailey D.G., Malcolm J., Arnold O. et al. Grapefruit juice-drug interactions. Br. J. Clin. Pharmacol. 1998; 46: 101-110.
30. Sullivan DM, Ford MA and Boyden TW. Grapefruit juice and the response to warfarin. Am J Health Syst Pharm 1998; 55: 1581–1583.
31. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin. Pharmacol. Ther. 2001; 69: 14-23.
32. Rodriguez-Fragoso L, Martinez-Arismendi JL, Orosco-Bustos D, Reyes-E Jorge, Torres E, Burchiel SW. Potential risks resulting from fruit/ vegetable-drug interactions: effects on drug -metabolkizing enzymes and drug transporters. J Food Sci. 2011 May;76(4): R112-24. doi: 10.1111/j.1750-3841.2011.02155.x. Review.
33. Engelsen J, Nielsen J.D, Hansen K.E. Effect of coenzyme Q10 and ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment: a randomized double-blind, placebo-controlled cross-over trial. Ugeskr Laeger. 2003; 165: 1868-1871.