Warfarin Azapropazone

Anticoagulant (warfarin) and antiplatelet agents (ticlopidine, clopidogrel) reduced platelet adhesiveness and G1 tract damage by NSAIDs increase risk of alimentary bleeding (notably with azapropazone). Phenylbutazone, and probably azapropazone, inhibit the metabolism of warfarin, increasing its effect. 

K. J. Fehske, U. Schlafer, U. WoUert, and W. E. Muller, Characterization of an important drug binding area on human serum albumin, including the high-affinity binding sites of warfarin and azapropazone. Mo/. Pharmacd., 21 387 (1982). 

McElnay JC, D Arcy PF. Interaction between azapropazone and warfarin. Experientia 1978 34(10) 1320-I. 

Oral anticoagulants Phenylbutazone Oxyphenbutazone Azapropazone Inhibition of metabolism of S-warfarin, increasing anticoagulant effect Avoid NSAIDs if possible careful monitoring when unavoidable (note also pharmacodynamic interactions)... 

HSA bears structural and functional resemblance to BSA, and HSA-type CSPs [164] also show similar enantioselective binding preferences for acidic and neutral drug molecules, such as 2-aryloxypropanoic acids [165], warfarin [166] and benzodiazepines [167]. The chiral recognition mechanism of HSA has been the subject of a number of investigations [168], which revealed that enantioselective binding occurs primarily at two well-defined hydrophobic sites. Acidic drugs have been shown to bind preferentially to the so-called warfarin-azapropazone (site I) and neutral drugs to the indol-benzodiazepine site (site II). 

The anticoagulant effects of warfarin are markedly increased by azapropazone, oxyphenbutazone and phenylbutazone. Concurrent use should be avoided because serious bleeding can occur. Feprazone appears to interact similarly. 

A woman taking digoxin, furosemide, spironolactone, allopurinol, and warfarin (prothrombin ratio 2.8) developed haematemesis within 4 days of starting to take azapropazone 300 mg four times a day. Her prothrombin ratio was found to have risen to 15.7. Subsequent gastroscopic examination revealed a benign ulcer, the presumed site of the bleeding. ... 

At least 12 other patients are reported to have developed this interaction. Bruising or bleeding (melaena, epistaxis, haematuria) and prolonged prothrombin times have occurred within a few days of starting azapropa-zone. Three patients died. " Another patient taking warfarin and azapropazone, diclofenac and co-proxamol had an increase in prothrombin time. ... 

Green AE, Hort JF, Korn HET, Leach H. Potentiation of warfarin by azapropazone, 5A47... 

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