Warfarin Aminosalicylates

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Self TH. Interaction of warfarin and aminosalicylic acid. JAMA 1973 223(11) 1285. 

A report attributes bleeding in a patient taking warfarin to the concurrent use of isoniazid. Another report describes a markedly increased anticoagulant response in a patient taking warfarin when the dose was doubled and aminosalicylic acid and isoniazid were started. In one study, isoniazid inhibited warfarin metabolism in vitro. 

Another patient taking digoxin, potassium chloride, docusate, diazepam and warfarin 2.5 mg daily, was also given aminosalicylic acid 12 g, isoniazid 300 mg and pyridoxine 100 mg daily, and at the same time the warfarin dose was doubled to 5 mg daily. His prothrombin time increased from 18 to 130 seconds over 20 days but no signs of haemorrhage were... 

These two isolated cases of possible interactions are far from conclusive, and the interactions of warfarin with isoniazid and aminosalicylic acid are not established. Nevertheless, given that the in vitro data suggest that isoniazid might inhibit warfarin metabolism, some caution might be appropriate. Further study is needed. 

Not understood. Sulfasalazine is broken down in the colon to a sulfonamide, sulfapyridine, and 5-aminosalicylic acid (mesalazine). Some sulfonamides , (p.376) are known inhibitors of warfarin metabolism, and increase the effects of warfarin. In contrast, in the case with sulfasalazine a marked decrease was noted. 

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