Warfarin Metabolism and Drug-Drug Interactions

  • Robert A. O’Reilly

Abstract

Drug interactions with warfarin vary from useful to disastrous. The pharmacologic combination of warfarin and a platelet inhibitor can be clinically efficacious. Contrarily, the increasing number of drugs that interact with warfarin can potentiate its anticoagulant effect and cause life-threatening hemorrhagic events. To avoid the futility of memorizing long lists of these drugs, guidelines will be presented for the prescribing physician. These concepts are understood best after the metabolism of warfarin in man is reviewed.

Keywords

Anticoagulant Therapy Short Bowel Syndrome Anticoagulant Effect Warfarin Concentration Racemic Warfarin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    P. J. Kearns, and R. A. O’Reilly, Bioavailability of warfarin in a patient with short bowel syndrome, J. Paren. Ent. Nutr. 10:10.0 (1986).Google Scholar
  2. 2.
    R. A. O’Reilly, Drug-induced vitamin K deficiency, resistance and drug interactions, in: “Prothrombin and Other Vitamin K Proteins,” Vol. II. W. H. Seegers and D. A. Walz, ed., CRC Press, Boca Raton (1986).Google Scholar
  3. 3.
    R. A. O’Reilly and P. A. Aggeler, Determinants of the response to oral anticoagulant drugs in man, Pharmacol. Rev. 22:35 (1970).PubMedGoogle Scholar
  4. 4.
    R. J. Lewis, W. F. Trager, K. K. Chan, A. Breckenridge, M. Orme, M. Roland, and W. Schary, Warfarin: stereochemical aspects of its metabolism and the interaction with phenylbutazone, J. Clin. Invest. 53:1607 (1974).PubMedCrossRefGoogle Scholar
  5. 5.
    R. A. O’Reilly, Anticoagulant, antithrombotic, and thrombolytic drugs, in: “Goodman and Gilman’s The Pharmacological Basis of Therapeutics,” A. G. Gilman, L. S. Goodman, T. W. Rall, and F. Murad, eds., Chap. 58, Macmillan, New York (1985).Google Scholar
  6. 6.
    B. M. Rifkind, Lipid Research Clinics Program, J.A.M.A. 252:2547 (1984).CrossRefGoogle Scholar
  7. 7.
    R. A. O’Reilly, Drug interactions involving oral anticoagulants, Cardiovasc. Cl. 6:23 (1974).Google Scholar
  8. 8.
    D. B. Hunninghake and D. M. Hibbard, Influence of time intervals for cholestyramine dosing on the absorption of hydrochlorothiazide, Clin. Pharmacol Ther. 39:329 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    J. M. Van den Broek, H. C. Ten Wolde-Kraamwinkel, C. H. Kleinbloesem and D. D. Breimer, Effect of rifampicin treatment on in vitro drug-metabolizing activities in the pig, Biochem. Pharmacol. 33:325 (1984).PubMedCrossRefGoogle Scholar
  10. 10.
    R. A. O’Reilly, Interaction of chronic, daily warfarin therapy and rifampin, Ann. Int. Med. 83:506 (1975).PubMedCrossRefGoogle Scholar
  11. 11.
    R. A. O’Reilly, Lack of effect of mealtime wine on the hypoprothrombinemia or oral anticoagulants, Am. J. Med. Sci. 277:189 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    R. A. O’Reilly, Lack of effect of fortified wine ingested during fasting and anticoagulant therapy, Arch. Int. Med. 141:458 (1981).CrossRefGoogle Scholar
  13. 13.
    R. A. O’Reilly, M. A. Sahud, and P. M. Aggeler, Impact of aspirin and chlorthalidone on the pharmacodynamics of oral anticoagulant drugs in man, Ann N. Y. Acad. Sci. 179:173 (1971).PubMedCrossRefGoogle Scholar
  14. 14.
    R. A. O’Reilly, Interaction of spironolactone and racemic warfarin in man, Clin. Pharmacol. Ther. 27:198 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    P. G. Frick, G. Riedler, and H. Brogli, Dose response and minimal daily requirement for vitamin K in man, J. Appl. Physiol. 23:387 (1967).PubMedGoogle Scholar
  16. 16.
    L. Uotila, J. W. Suttie, Inhibition of vitamin K-dependent carboxylase in vitro by cefamandole and its structured analogs, J. Infect. Dis. 148:571 (1983).PubMedCrossRefGoogle Scholar
  17. 17.
    R. A. O’Reilly and D. A. Rytand, “Resistance” to warfarin due to unrecognized vitamin K supplementation, N. Engl. J. Med. 303:160 (1980).PubMedGoogle Scholar
  18. 18.
    S. J. Kempin, Warfarin resistance caused by broccoli, N. Engl. J. Med. 308:1229 (1983).PubMedCrossRefGoogle Scholar
  19. 19.
    R. A. O’Reilly, M. A. Sahud, and A. J. Robinson, Studies on the interaction of warfarin and Clofibrate in man, Throm. Diath. Haemorrh. 27:309 (1972).Google Scholar
  20. 20.
    R. A. O’Reilly, Editorial: complications of anticoagulant therapy, West. J. Med. 132:453 (1980).PubMedGoogle Scholar
  21. 21.
    T. W. Meade, Safety of oral anticoagulation, Lancet 1:1387 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    R. Hull, J. Hirsh, R. Jay, C. Carter, C. England, M. Gent, A. G. G. Turpie, D. McLoughlin, P. Dodd, M. Thomas, G. Raskob, and P. Ockelford, Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis, N. Engl.J. Med. 307:1676 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Robert A. O’Reilly
    • 1
  1. 1.Departments of Medicine, Santa Clara Valley Medical Center, Stanford University School of MedicineUniversity of California, San FranciscoSan JoseUSA

Personalised recommendations