Itraconazole Bromperidol

Furukori H, Kondo T, Yasui N, Otani K, Tokinaga N, Nagashima U, Kaneko S, Inoue Y. Effects of itraconazole on the steady-state plasma concentrations of bromperidol and reduced bromperidol in schizophrenic patients. Psychopharmacology (Berl) 1999 145(2) 189-92. 

Itraconazole increases the plasma levels of haloperidol, and its metabolite, reduced haloperidol Bromperidol may be similarly affected. 

A study in 8 patients found that plasma levels of bromperidol 12 or 24 mg daily, were increased by itraconazole 200 mg daily for 7 days. The average increase was approximately 87%, but there was wide variation between patients, with some being unaffeeted and others having increases of up to 302%. Levels of the metabolite of bromperidol, redueed bromperidol, were similarly increased, by up to 415%. ... 

It is likely that itraconazole inhibited the metabolism of bromperidol and haloperidol by CYP3A4. The wide variation in results may be attributed to interindividual variation in CYP3A4 activity. 

The clinical significance of the raised levels is unclear, although one study found an increase in neurological adverse effects with haloperidol. It may be prudent to monitor concurrent use, decreasing the haloperidol or bromperidol dose if adverse effects become troublesome. This interaction may be of more importance in those patients have less active CYP2D6, the predominant isoenzyme involved in the metabolism of haloperidol, as CYP3A4, which is inhibited by itraconazole, will then become more important. It is likely that other azoles that are potent inhibitors of CYP3A4, such as ketoconazole, would interact similarly, but this needs confirmation. 

---