Interactions of Warfarin

Abstract

In this article, the author reviews and updates the basis of interactions with warfarin, illustrated with appropriate examples. The interactions with drugs, medicinal herbs and foods are summarised. 28Cholestyramine binds vitamin K in the gut, thus preventing its absorption 18 . It also decreases the absorption and may interrupt the enterohepatic recirculation of warfarin, resulting in a reduced anticoagulant effect 19,20 .Colestipol does not affect the absorption of warfarin. When colestipol is administered with warfarin, no depressant effects on blood levels are seen 21 . Drugs affecting receptor sensitivityEstrogens increase the synthesis of various clotting factors and may thus reduce the effect of anticoagulants 22, 23 . Oral contraceptives increase clotting factor concentrations and inhibit warfarin metabolism. The net effect depends on balance between these factors. Oral contraceptives are generally contraindicated in most patients taking warfarin since they are trombogenic 1, 24 .Steroids with anabolic or androgenic properties, such as oxymetholone 25, 26, 27 , stanozolol 28, 29 and danazol 30, 31, 32 , may potentiate the action of warfarin allegedly by reducing clotting factor synthesis. The 17-alpha-alkylated steroids appear to be more likely to induce this reaction than the non-substituted steroids 25, 26, 27, 33 . However, there has been a report of topically applied testosterone, which does not have 17-alpha-alkyl substituent, enhancing warfarin 34 .Diuretics may antagonise the action of warfarin by two pharmacodynamic mechanisms 18 : (a) patients in cardiac failure have impaired clotting factor synthesis due to hepatic congestion -correction of this state leads to increased clotting factor synthesis; (b) diuretics also reduce the plasma volume producing an increased concentration of clotting factors which may alter the anticoagulant effect of warfarin 35 . Chlorthalidone 36 and spironolactone 35 have both been associated with a reduction of warfarin activity probably as a consequence of diuresis concentrating the circulating clotting factors. Bumetanide, furosemide and thiazides appear to have no effect on warfarin 23 .Certain cephalosporines, such as cefotetan, cefamandole, cefoperazone, or moxalactam may cause marked hypoprothrombinemia and/or prolonged bleeding time at concurrent use with warfarin 38, 39, 40, 41 . The main mechanism of interaction consists in decreasing synthesis of vitamin K-dependent clotting factors.Clofibrate may potentiate warfarin action, probably by altering receptor sensitivity 23, 37 . Although clofibrate displaces warfarin from albumin binding sites this does not appear to be a principal mechanism of the interaction 42 .Drugs altering thyroid function may affect anticoagulant control, since rates of synthesis and degradation of clotting factors are dependent on thyroid function 7 . Thyroid compounds do enhance the activity of oral anticoagulants by increased metabolism of clotting factors 12 . Dextrothyroxine increases the anticoagulant effect of warfarin ...

COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

“…Special warnings and precautions of use. Concerns were raised over the concomitant use of P. veris and warfarin ( Řehulková, 2001 ).…”

Evidence-based drug–herbal interactions

“…In addition, warfarin inhibits activation of vitamin K-dependent regulatory proteins C and S (Rehulkova, 2001;Hirsh et al, 1992). Fluctuations in the ingestion of sources of vitamin K such as green, leafy vegetables and certain vegetable oils may effect the hypoprothrombinemic response to warfarin, and therefore may require dosage adjustment of warfarin dosage.…”

“…The main enzyme responsible for S-warfarin metabolism is CYP2C9 and any factor that modifies the expression and activity of CYP2C9 can influence the anticoagulant response (Greenblatt and von Moltke, 2005). Many warfarindrug interactions have been attributed to the metabolic inhibition of the S-enantiomer by CYP2C9 (Rehulkova, 2001;Wittkowsky, 2001). It is less likely that significant warfarindrug or herbal interactions would occur if the minor CYP3A4 metabolic pathway of S-warfarin is inhibited.…”