Erythromycin Acenocoumarol

Erythromycin may potentiate acenocoumarol anticoagulant treatment, as reported in a 68-year-old man on stable anticoagulation with acenocoumarol 3 mg/day who took erythromycin ethylsuccinate 1.5 g/day (79). 

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... 

Acenocoumarol. Haematuria occurred in a patient stabilised on acenocoumarol on the last day of a 14-day course of erythromycin. Another patient stabilised on acenocoumarol with an INR in the range of 3 to 4.5 was found to have an INR of 15 a week after starting to take erythromycin ethylsuccinate 1.5 g daily but no bleeding was seen. Conversely, in one cohort study in patients taking acenocoumarol or phenprocoumon, no cases of over-anticoagulation (11 greater than 6) occurred in patients treated with erythromycin (78 patients received this antibacterial). Note that this study did show an increase for clarithromycin, see above. 

Erythromycin is a known inhibitor of the cytochrome P450 isoenzyme CYP3A4. However, this isoenzyme has only a minor role in the metabolism of warfarin , (p.358), specifically the less active R-isomer of warfarin. Consequently, only minor increases in the levels of warfarin have been seen in pharmacokinetic studies, which would generally not be expected to be clinically relevant. However, it is possible that even these small changes might be important in a very few patients, particularly those with a low prothrombin complex aetivity. Other macrolides (azithromycin, clarithromycin, dirithromycin, roxithromycin) have less effect on CYP3A4 than erythromycin, and consequently would be expected to have even less effect on the pharmacokinetics of warfarin or acenocoumarol, which is borne out in the few studies available. Nevertheless, cases of interactions have been reported for nearly all these macrolides. Moreover, one cohort study found that clarithromycin increased the risk of an interaction and erythromycin did not. It is possible that there is some other, as yet unidentified, mechanism involved. Alternatively, it is equally possible that the relatively few cases just represent idiosyncratic effects attributable to other factors, and not to any interaction (see also Coumarins -i- Antibacterials , p.365). 

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