Interactions between nexium-i-v(esomeprazole) and Fazaclo (clozapine)
clozapine and esomeprazole (Moderate Drug-Drug)
MONITOR: Coadministration with omeprazole may decrease the plasma concentrations of clozapine. The proposed mechanism is omeprazole induction of clozapine metabolism via CYP450 1A2. Two case reports describe patients stabilized on clozapine who experienced a 42% and 45% decrease in their plasma clozapine levels following the addition of omeprazole. No changes in their clinical presentation were noted, however. In a retrospective study of the medical files of 13 psychiatric patients receiving both clozapine and omeprazole, a switch to pantoprazole was associated with a significant rise of the serum clozapine levels in all nonsmokers relative to smokers, although the daily dosage of clozapine was unchanged. Presumably, the increase was due to the discontinuation of CYP450 1A2 induction by omeprazole in nonsmokers, whereas the isoenzyme remained induced in patients who smoked, as cigarette smoke is a known inducer of CYP450 1A2. Theoretically, this interaction could also occur with esomeprazole, the S-enantiomer of omeprazole.
MANAGEMENT: Pharmacologic response and serum clozapine levels should be monitored more closely whenever omeprazole or esomeprazole is added to or withdrawn from therapy, and the clozapine dosage adjusted as necessary. Alternatively, use of another proton pump inhibitor such as pantoprazole may be considered.
