Azapropazone interaction

Azapropazone has the same pattern of interactions as phenylbutazone with oral anticoagulants (SEDA-2, 98). 

Geaney DP, Carver JG, Aronson JK, Warlow CP. Interaction of azapropazone with phenytoin. BMJ (Clin Res Ed) 1982 284(6326) 1373. 

Andreasen PB, Simonsen K, Brocks K, Dimo B, Bouchelouche P. Hypoglycaemia induced by azapropazone tolbutamide interaction. Br J Clin Pharmacol 1981 12(4) 581-3. 

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)... 

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. 

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. ... 

Consider also azapropazone, phenylbutazone, and oxyphenbuta-zone , (p.498) and the salicylates , (p.502) for related drugs that do have adverse interactions with antidiabetics. 

The information regarding an interaction between azapropazone and the sulphonylureas seems to be limited to the cases and small study involving tolbutamide. Nevertheless, the manufacturers of azapropazone say that the concurrent use of sulphonylureas is not recommended."... 

The most likely explanation is that azapropazone inhibits the liver enzymes concerned with the metabolism of phenytoin, resulting in its accumulation. It also seems possible that azapropazone displaces phenytoin from its plasma protein binding sites so that levels of unbound (and active) phenytoin are increased. Information seems to be limited to the reports cited, but it appears to be a clinically important interaction. The incidence is uncertain, but an interaction occurred in all 5 of the subjects in the study cited. The manufacturers contraindicate azapropazone in patients taking phenytoin. ... 

The importance of the interaction with azapropazone, etoricoxib, fenbufen and tiaprofenic acid is not known. In most cases changes to doses are unlikely to be necessary, but remain aware of the potential for an interaction. No special precautions would appear to be necessary with isoxicam, ketoprofen, meloxicam, piroxicam, and rofecoxib. More study is needed in most cases, but especially with ibuprofen, where the evidence is conflicting (although note that the one study reporting a significant interaction was poor). 

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