Risperidone metabolizing enzymes

Inhibits metabolizing enzymes (caffeine inhibits CYPl A2, which metabolizes clozapine). Inhibition of CYP by ginkgo t alpha-1 effects of risperidone. Valerian may worsen the sedative properties of haloperidol. Hops and phenothiazine have been associated with hyperthermia in dogs... 

Risperidone is metabolized primarily by CYP 2D6 (Byerly and De-Vane 1996). Medications that inhibit this enzyme, such as many of the SSRls, cause increases in plasma risperidone levels. Pharmacodynamic interactions may occur when risperidone is combined with medications that share a similar physiological effect, such as orthostatic hypotension. 

Phenytoin, an enzyme inducer, can reduce clozapine plasma levels. There have been two reported cases of risperidone causing an increase in clozapine plasma levels however, because this agent is not an inhibitor of 1A2, the mechanisms for this increase are unclear. Nefazodone administered with clozapine has had minimal effects on clozapine s metabolism (329). 

Carbamazepine induces CYP3A, and the metabolism of risperidone, which mainly involves CYP2D6, may also involve CYP3A. Carbamazepine can therefore reduce risperidone plasma concentrations (SEDA-22, 71). However, since carbamazepine alters the biotransformation of many agents, non-specific enzyme induction has been suggested for the risperidone and carbamazepine interaction (240). 

Since risperidone is metabolized by CYP450 2D6, any agent that inhibits this enzyme could theoretically raise risperidone plasma levels however, dose reduction of risperidone is usually not necessary when such combinations are used... 

Carbamazepinewasfound to decrease the plasma levels of phenothiazines by as much as 50% (described with chlorpromazine, perphenazine, and fluphenazine). It has been reported to decrease the serum levels of clozapine by about60-85% due to its hepatic cytochrome P450 (CYP) enzyme-inducing properties. Loxapine may induce carbamazepine metabolism. Carbamazepine has been shown to reduce the plasma levels of risperidone by as much as 50%, while it increases olanzapine clearance by 44% and reduces its half-life by 20%. Carbamazepine increases aripiprazole metabolism through CYP3A4 induction. Thus, the aripiprazoie dose should be doubled. 

For instance, there are 78 reported variants of CYP 2D6 that associated with adverse drug reactions. Many of these polymorphic genes encode inactive enzymes. However, these inactive enzymes may produce adverse drug reactions among patients because of their poor metabolic activity (e.g., the adverse effects of the neuroleptic risperidone) [29]. 

Carbamazepine is a known potent enzyme inducer, which appears to increase the metabolism of risperidone by the cytochrome P450 isoenzyme CYP2D6 (although other isoenzymes may play a part). The extent of the interaction appears to be related to CYP2D6 genotype (see Genetic factors , (p.4)). Oxcarbazepine is not known to affect CYP2D6-mediated metabolism. 

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