Cimetidine Acenocoumarol

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... 

Beyond those in vivo examples depicted in Table 4, there are some in vitro data suggesting stereoselective drug interactions with oral anticoagulants. For example, Hermans and Thijssen [68] investigated the potential of metabolic interactions in vitro between warfarin or acenocou-marol and cimetidine, propafenone, sulphaphenazole, or omeprazole using human liver microsomes. Sulphaphenazole competitively inhibited the 7- and in some experiments the 6-hydroxylation of S-warfarin and R- and S-acenocoumarol. Omeprazole partly inhibited the 6- and 7-hydroxylation of R-warfarin, R-acenocoumarol, and S-acenocoumarol [68]. 

The anticoagulant effects of warfarin can be increased by cimeti-dine. The effect is generally minor to modest, although severe bleeding has been reported in a few cases. Acenocoumarol seems to interact similarly, but phenprocoumon appears not to be affected. In one patient the effects of phenindione were modestly increased by cimetidine. Famotidine, nizatidine, ranitidine and roxatidine normally do not appear to interact, although isolated cases of bleeding have been reported. 

In 3 studies, the AUC of single-dose acenocoumarol was increased by cimetidine, and the prothrombin time prolonged, " with the effect greatest for A-acenocoumarol. However, another study found no interaction. Data from one patient taking acenocoumarol and one taking phenindione showed that cimetidine increased their anticoagulant effects. In one study in patients stabilised on phenprocoumon, cimetidine 400 mg twice daily did not alter the pharmacokinetics of phenprocoumon nor its anticoagulant effect. ... 

Cimetidine also appears to interact with acenocoumarol, but not phenprocoumon. The other H2-receptor antagonists normally do not act as enzyme inhibitors. 

The interaction between warfarin and cimetidine is well documented, well established and potentially clinically important. Its effects are generally modest, but rarely, patients have shown a marked interaction. Because of this unpredictability, and to avoid bleeding, the response should be monitored well in every patient when cimetidine is first added, being alert for the need to reduce the warfarin dosage. The onset of the interaction appears rapid effects have been seen within days, and even as early as 24 hours. The effect of low non-prescription doses of cimetidine on warfarin do not appear to have been studied. Acenocoumarol is reported to in-teraet similarly, and there is one case of phenindione being affected. Expect other coumarins and indanediones to behave in the same way, with the possible exception of phenprocoumon, which was not affected in one study. 

Thijssen HHW, Janssen GMJ, BaarsLGML Lackof effect of cimetidine on iharmacodynam-ics and kinetics of single oral doses of R- and S-acenocoumarol. EurJ CUn Pharmacol (1986) 30, 619-23. 

Neither cimetidine nor rifampicin had any clinically relevant effect on the pharmacokinetics of nicorandil. Nicorandil did not alter the anticoagulant effects of acenocoumarol. Although animal studies surest antagonism of effects, a study in patients found no pharmacodynamic interaction between nicorandil and glibenclamide. Nicorandil may potentiate the hypotensive effects of other vasodilators, tricyclic antidepressants and alcohol. 

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