Warfarin drug interactions: a comparative evaluation of the lists provided by five information sources
Detecting potential drug interactions can lead to early interventions that protect patients from serious drug-related problems. The aim of this study was to evaluate the agreement among the lists of warfarin interactions provided by five information sources.
The lists of warfarin interactions and the corresponding severity ratings and documentation levels presented by the three compendia and by the World Health Organization (WHO) Model Formulary were all compared, and each list was compared to that provided on the package insert of Marevan, a brand of warfarin. The compendia used were: Drug Interaction Facts, Drug Interactions: Analysis and Management and DRUG–REAX. A kappa coefficient was used to calculate the agreement among the sources.
A total of 537 interactions were listed. Only 13 (2.4%) were common to the five sources. The global Fleiss’ kappa coefficient was −0.0080, which indicated poor agreement. Eleven warfarin interactions appeared only in the Marevan package insert. Importantly, 243 interactions (45.3% of the total) were deemed significant in at least one compendium. Only two warfarin interactions were reported as critical by all three compendia and by WHO. The most critical interactions cited by the compendia were missing from the package insert.
Poor agreement was found among five sources listing warfarin interactions. Potentially severe clinical consequences might occur due to these discrepant recommendations. Finally, the lack of standard terminology and clinical guidance, as well as the possible inaccuracy of severity ratings and documentation might contribute to heterogeneous procedures in clinical practice.
KeywordsWarfarin Drug toxicity Herb–drug interactions Food–drug interactions Drug labeling
- 1.Kohn LT, Corrigan JM, Donaldson MS (2000) To err is human: building a safer health system. National Academy Press, Washington D.C.Google Scholar
- 7.Stockley IH (2010) Drug interactions. The Pharmaceutical Press, LondonGoogle Scholar
- 11.Micromedex. Drug–Reax System (2010) Internet database. Available at: http://www.thomsonhc.com/hcs/librarian/PFDefaultActionId/hcs.Interactions.WordWheel. Accessed 31 Oct 2010
- 12.Hansten PD, Horn JR (2010) Drug interactions analysis & management. Wolters Kluwer, Saint LouisGoogle Scholar
- 15.Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK, Kamali F (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106:2329–2333PubMedCrossRefGoogle Scholar
- 24.Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, Baird MF, Acton RT (2008) Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African–American and European–American patients on warfarin. Clin Pharmacol Ther 83:312–321PubMedCrossRefGoogle Scholar
- 36.Tatro DS (2011) Drug interaction facts. Wolters Kluwer, Saint LouisGoogle Scholar
- 37.Stuart MC, Kouimtzi M, Hill SR (eds) (2009) WHO Model Formulary 2008. World Health Organization. Available at http://whqlibdoc.who.int/publications/2009/9789241547659_eng.pdf. Accessed 21 May 2011