Phenytoin Azapropazone

Azapropazone Phenytoin Risk of phenytoin toxicity altered relation between total phenytoin concentration and effect Displacement from plasma proteins and inhibition of phenytoin metabolism... 

Antiepileptics azapropazone and phenylbutazone inhibit the metabolism of phenytoin and sodium valproate, increasing their risk of toxicity. 

Azapropazone has the same pattern of interactions as phenylbutazone with phenytoin (6,7). 

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

A patient taking phenytoin developed phenytoin toxicity within 2 weeks of starting azapropazone 600 mg twice daily. Further study in 5 healthy subjects given phenytoin 125 to 250 mg daily found that azapropazone 600 mg twice daily, briefly decreased their mean serum phenytoin levels from 5 to 3.7 micrograms/mL before they rose steadily over the next 7 days to 10.5 micrograms/mL. An extension of this study is described elsewhere. ... 

Another report describes phenytoin toxicity in a woman taking phenytoin and primidone when fenclofenac was replaced by azapropazone 1.2 g daily. 

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. ... 

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