Coumarin anticoagulants reduction

Hilgard P, Maat B. Mechanism of lung tumour colony reduction caused by coumarin anticoagulation. Eur J Cancer 1979 15(2) 183-7. 

The combination of dipyridamole and coumarin anticoagulants does not alter the prothrombin time, but might cause an increased risk of serious bleeding when compared with anticoagulants alone. There is some evidence that the risk of bleeding may be lower, without a reduction in efficacy, if the INR is maintained within a lower range. 

The loop diuretics, bumetanide, furosemide and torasemide, the potassium-sparing diuretic spironolactone, and the thiazides chlortalidone and chlorothiazide, have all been shown either not to interact or to cause only a small reduction in the effects of the coumarin anticoagulants of minimal or no clinical importance. The lack of reports of clinically relevant interactions su ests that, in general, diuretics do not interact with anticoagulants. The possible exception is etacrynic acid, which on rare occasions has caused a marked increase in the effects of warfarin. 

The C=0 stretching frequency of a number of 4-hydroxy- and 4-alkoxy-coumarins, including several anticoagulant drugs, has been identified by isotopic replacement of the carbonyl carbon atom by 3C as the highest frequency band in the 1750-1550 cm-1 region. Introduction of the isotopic atom causes a reduction in the C=0 frequency of ca. 30 cm-1 (82JHC475). 

A reduction in efficacy due to an interaction can sometimes be just as harmful as an increase patients taking warfarin who are given rifampicin need more warfarin to maintain adequate and protective anticoagulation (see Coumarins + Antibacterials Rifamycins , p.375), while patients taking tetracyclines , (p.347) or quinolones , (p.332) need to avoid antacids and milky foods (or separate their ingestion) because the effects of these antibacterials can be reduced or even abolished if admixture occurs in the gut. 

The anticoagulant effects of phenprocoumon and warfarin can be reduced by colestyramine, especially if the coumarin is given at the same time. An isolated report describes unexpected sensitivity to warfarin in a patient taking colestyramine, which was attributed to a possible reduction in vitamin K absorption with colestyramine. Colestipol did not alter the absorption or effect of phenprocoumon or warfarin and colesevelam did not alter the pharmacokinetics of warfarin. 

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