Isoniazid in slow acetylators

A/-acetyltransferase 2 Low activity in about 60% of Caucasian populations. High incidence of adverse events from the drug isoniazide in slow acetylators. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

This greater incidence in toxicity in slow acetylators corresponded with a greater increase in the plasma level of diphenylhydantoin when the drugs were taken in combination. This was due to higher plasma levels of isoniazid in slow acetylators, causing a greater degree of inhibition of diphenylhydantoin metabolism. 

---