Aripiprazole metabolism

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. 

Aripiprazole shares a similar metabolic profile to risperidone, being metabolized by CYP2D6 and 3A4 (Kubo etal, 2005). Few studies exist to compare and contrast aripiprazole effects in different ethnic groups. A recent study indicated that Chinese... 

This group includes risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole. But all these agents cause dose-related EPS and appear in general more likely to cause diabetes and other metabolic problems than some of the older drugs (see Duggan et ah, 2005). 

Aripiprazole is hepatically metabolized, mainly by two cytochrome P450 enzymes CYP 2D6 and CYP 3A4. Therefore, dosage adjustments are necessary when this medication is given with other medications that either inhibit or induce these enzymes. For example, the dose of aripiprazole should be halved when this medication is given with ketoconazole, a CYP 3A4 inhibitor, or at least decreased when given with fluoxetine, a CYP 2D6 inhibitor. When aripiprazole is given with CYP 3A4 inducers such as carbamazepine, the dose should be doubled. 

A 34-year-old African-American woman with schizophrenia had nausea, vomiting, and malaise for 3-4 days shortly after starting to take aripiprazole therapy. She had hyperglycaemia and a metabolic acidosis, which responded rapidly to standard treatment and did not recur when aripiprazole was withdrawn. 

ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL RIFABUTIN, RIFAMPICIN 1 levels of these antipsychotics t metabolism Watch for poor response to these antipsychotics consider increasing the dose... 

ARIPIPRAZOLE ITRACONAZOLE, KETOCONAZOLE t aripiprazole levels Inhibition of metabolism L dose of aripiprazole... 

ARIPIPRAZOLE NNRTIs L efficacy of aripiprazole t CYP3A4-mediated metabolism of aripiprazole Monitor patient closely, and t dose of aripiprazole as necessary... 

ARIPIPRAZOLE, HALOPERIDOL, CLOZAPINE, PIMOZIDE, RISPERIDONE, SERTINDOLE PROTEASE INHIBITORS Possibly T levels of antipsychotic Inhibition of CYP3A4- and/or CYP2D6-mediated metabolism Avoid co-administration of clozapine with ritonavir, and pimozide or sertindole with protease inhibitors. Use other antipsychotics with caution as 1 dose may be required with risperidone, watch closely for extrapyramidal side-effects and neuroepileptic malignant syndrome... 

ARIPIPRAZOLE, CLOZAPINE, HALOPERIDOL, PERPHENAZINE, RISPERIDONE, SERTINDOLE SSRIs Possible t plasma concentrations of these antipsychotics Inhibition of CYP2D6-mediated metabolism of these drugs. The clinical significance of this depends upon whether alternative pathways of metabolism of these substrates are also inhibited by co-adminis-tered drugs. The risk is theoretically greater with clozapine, haloperidol and olanzapine because their CYPl A2-mediated metabolism Is also Inhibited by SSRIs Warn patients to report T side-effects of these drugs, and consider reducing the dose of the antipsychotic... 

Aripiprazole 10 to 30 mg daily had no significant effects on the metabolism of dextromethorphan (CYP2D6 and CYP3A4 substrate), warfarin (CYP2C9 substrate) and omeprazole (CYP2C19 substrate). Aripiprazole is not expected to affect CYPl A2-mediated metabolism. The manufacturers therefore conclude that aripiprazole is unlikely to have clinically significant interactions with drugs that are substrates for these isoenzymes. ... 

Aripiprazole Of 125 patients who were stabilized on aripiprazole for 6-18 weeks before double-blind random assignment to aripiprazole or placebo for 26 weeks, 45 (36%) met criteria for metabolic syndrome at entry [38 ]. The proportions of patients with metabolic syndrome were similar in the placebo and aripiprazole groups at both baseline and week 26. There were no significant changes in any of the individual components of metabolic syndrome between aripiprazole- and placebo-treated patients during maintenance phase treatment. 

Aripiprazole for 8 weeks has been used in 24 patients with hyperprolactinemia induced by risperidone, amisulpride, or sulpiride [132 ]. Prolactin concentrations fell from 77 to 18 ng/ml in those taking risperidone, from 145 to 128 in those taking amisulpride, and from 71 to 43 ng/ml in those taking sulpiride. Aripiprazole had no significant effect on metabolic measures or scales of movement adverse reactions. Nevertheless, it should be remembered that antipsychotic drug combinations are not approved for any indication. 

Hoffmann VP, Case M, Stauffer VL, Jacobson JG, Conley RR. Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasi-done or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controlled clinical trials. J Clin Psychopharma-col 2010 30 656-60. 

Metabolism A 6-month, retrospective chart review compared patients on aripiprazole alone to aripiprazole and an SSRI (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine) or aripiprazole and bupropion [92 ]. Only the combination of aripiprazole and an SSRI had statistically significant weight gain, thus it was hypothesised that in the presence of high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2c receptor. 

Drug-drug interactions The pharmacokinetics of aripiprazole, with and without coadministration of SSRIs, were compared according to CYP2D6 genotypes [93. Paroxetine decreased systemic clearance of aripiprazole by 58% and 23% in CYP2D6 extensive metaboUzers and intermediate metabolizers, respectively, while fluvoxamine had no effect... 

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