Acenocoumarol Benzbromarone

Noninterfering amiloride, acebutolol, acenocoumarol, acetaminophen, aspirin, allopuri-nol, ambroxol, amoxicillin, atenolol, bendroflumethiazide, benzbromarone, bezafibrate, biperiden, bisacodyl, bromazepam, butizide, captopril, cimetidine, ciprofloxacin, clobu-tinol, clonidine, cotinine, diazepam, diclofenac, digitoxin, digoxin, dihydrocodeine, dihy-droergotamine, diltiazem, doxepin, doxycycline, enalapril, erythromycin, fenoterol, furosemide, glibenclamide, heparin, h3qjoxanthine, ibuprofen, indomethacin, isosorbide... 

Benzbromarone selectively inhibits the metabolism of S-warfarin by the cytochrome P450 isoenzyme CYP2C9 so that its effects are increased. The metabolism of the 7 -warfarin remains unchanged. Acenocoumarol and phenprocoumon are also known to be metabolised by CYP2C9, and would therefore be expected to interact similarly. Benziodarone is another ben-zofuran derivative with a similar structure to benzbromarone, and therefore probably interacts via a similar mechanism. 

The anticoagulant effects of warfarin are increased by benzbromarone and bleeding has been seen. Simiiariy, the anticoaguiant effects of acenocoumarol, ethyl biscoumacetate, diphenadione and warfarin are increased by benziodarone. 

Early information about benzbromarone noted that no increase in the anticoagulant effects of the coumarins acenocoumarol and ethyl biscoumacetate or the indanedione phenindione had been seen in a few patients also given benzbromarone. ... 

The interaction between warfarin and benzbromarone or benziodarone is established and elinieally important. If benzbromarone is added to warfarin monitor prothrombin times and be alert for the need to reduce the dosage by about one-third to prevent over-anticoagulation. Information about other coumarins is limited, but what is known about the mechanism of action suggests that acenocoumarol and phenprocoumon would also be predicted to interact, and this has been shown for benziodarone and acenocoumarol or phenprocoumon, in a few patients. The limited evidence suggesting an interaction with some indanediones also suggests that some caution is appropriate with these drugs as well. 

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