Interaction of olanzapine with fluvoxamine

Jong, J. de; Hoogenboom, Britt; Troostwijk, L D van; Haan, L. de

doi:10.1007/s002130100713

Cited by 29 publications

(10 citation statements)

References 1 publication

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“…21 Because the upper limit of the therapeutic window for olanzapine is not yet clearly defined, we recommend judicious therapeutic drug monitoring, with potential further titration of the olanzapine dosage during olanzapine and fluvoxamine combination therapy. 22 This therapeutic strategy may be best suited for patients who can be compliant to both olanzapine and fluvoxamine coadministration. Insofar as the selectivity of CYP1A2 inhibition is concerned, there is now general agreement that fluvoxamine can inhibit other (eg, CYP2C19) drug metabolizing enzymes.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Fluvoxamine as an Adjunct to Reduce Olanzapine Therapeutic Dose Requirements

Albers¹,

Özdemir²,

Marder³

et al. 2005

Journal of Clinical Psychopharmacology

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Despite the advances in antipsychotic pharmacotherapy over the past decade, many atypical antipsychotic agents are not readily accessible by patients with major psychosis or in developing countries where the acquisition costs may be prohibitive. Olanzapine is an efficacious and widely prescribed atypical antipsychotic agent. In theory, olanzapine therapeutic dose requirement may be reduced during concurrent treatment with inhibitors of drug metabolism. In vitro studies suggest that smoking-inducible cytochrome P450 (CYP) 1A2 contributes to formation of the metabolite 4'-N-desmethylolanzapine. The present prospective study tested the hypothesis that olanzapine steady-state doses can be significantly decreased by coadministration of a low subclinical dose of fluvoxamine, a potent inhibitor of cytochrome P450 1A2. The study design followed a targeted "at-risk" population approach with a focus on smokers who were likely to exhibit increased cytochrome P450 1A2 expression. Patients with stable psychotic illness (N = 10 men, all smokers) and receiving chronic olanzapine treatment were evaluated for steady-state plasma concentrations of olanzapine and 4'-N-desmethylolanzapine. Subsequently, olanzapine dose was reduced from 17.5 +/- 4.2 mg/d (mean +/- SD) to 13.0 +/- 3.3 mg/d, and a nontherapeutic dose of fluvoxamine (25 mg/d, PO) was added to regimen. Patients were reevaluated at 2, 4, and 6 weeks during olanzapine-fluvoxamine cotreatment. There was no significant change in olanzapine plasma concentration, antipsychotic response, or metabolic indices (eg, serum glucose and lipids) after dose reduction in the presence of fluvoxamine (P > 0.05). 4'-N-desmethylolanzapine/olanzapine metabolic ratio decreased from 0.45 +/- 0.20 at baseline to 0.25 +/- 0.11 at week 6, suggesting inhibition of the cytochrome P450 1A2-mediated olanzapine 4'-N-demethylation by fluvoxamine (P < 0.05). In conclusion, this prospective pilot study suggests that a 26% reduction in olanzapine therapeutic dose requirement may be achieved by coadministration of a nontherapeutic oral dose of fluvoxamine.

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Section: Discussionmentioning

confidence: 99%

Low-Dose Fluvoxamine as an Adjunct to Reduce Olanzapine Therapeutic Dose Requirements

Albers¹,

Özdemir²,

Marder³

et al. 2005

Journal of Clinical Psychopharmacology

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“…Several studies have documented that fluvoxamine (50 --100 mg/day) may also elevate plasma levels of olanzapine approximately twofold, presumably through inhibition of CYP1A2, with possible ADR occurrence [63][64][65][66]. The magnitude of the effect of fluvoxamine on plasma levels of olanzapine is lower than observed with clozapine, as olanzapine is metabolized by multiple enzyme systems, namely UGT, whose activity may not be affected by fluvoxamine.…”

Section: {{{mentioning

confidence: 93%

“…Inhibition of CYP1A2 [63][64][65][66] Risperidone No significant changes in plasma risperidone concentrations at fluvoxamine dosage of 100 mg/day, increase by 26% at fluvoxamine dose of 200 mg/day Inhibition of CYP2D6 and CYP3A4 [68] Quetiapine Increase in plasma concentrations of quetiapine by 159% Inhibition of CYP3A4 [45] Aripiprazole Decrease by 40% in systemic clearance of aripiprazole Inhibition of CYP3A4 [53] Asenapine Increase by 29% in the AUC of asenapine at fluvoxamine dosage of 50 mg/day Inhibition of CYP1A2 [25,26] Sertraline Risperidone Increased plasma concentrations of risperidone (36 --52%) only at high doses of sertraline (150 mg/day) Inhibition of CYP2D6 [69] Citalopram/ escitalopram Aripiprazole Minimal increase (by 20%) in plasma concentrations of aripiprazole and dehydroaripiprazole Inhibition of CYP2D6 [46] Duloxetine Risperidone Minimal increase (by 26%) in plasma concentrations of the active moiety of risperidone Inhibition of CYP2D6 [83] Olanzapine No change or minimal increase in plasma olanzapine concentrations Inhibition of CYP2D6 (?) [82,83] AUC: Area under the curve; CYP: Cytochrome P450.…”

Section: Risperidonementioning

confidence: 99%

Clinically relevant interactions between newer antidepressants and second-generation antipsychotics

Spina

León

2014

Expert Opinion on Drug Metabolism & Toxicology

100

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More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes.

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“…Elevated levels of clozapine (up to 10-fold) in the presence of fluvoxamine have been reported [166][167][168] leading in Extrapyramidal symptoms (tremor, rigid movements) mydriasis [177][178][179][180]246] Ropivacaine CL (by 60%) Unknown [190] Tacrine CL (by 90%) Decrease of tacrine-induced hepatotoxicity? [186,247] Theophylline Css (by 2-fold) Migraine, tiredness, vomiting, tachycardia, anorexia, seizures [192][193][194] Thioridazine Css (up to 3-fold) Increased risk of severe symptoms (cardiotoxicity) and sudden death CYP2C19 [164] Tizanidine AUC (33-fold) Increased intensity and duration of relaxant effects [181] Tricyclic antidepressants AMT Css (by 2.5-fold) some patients to extremely high plasma levels (up to 4160 ng/mL), largely exceeding the upper limit of the therapeutic window [169].…”

Section: Fluvoxamine: the Paradigm Of Cyp1a2-related Drug Interactionmentioning

confidence: 99%

Pharmacogenetics of Cytochrome P450 (CYP) 1A2 and Variability in Psychotropic Drug Response

Carrillo¹

2006

CPSR

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Despite the availability of a wide range of different drug classes for the management of psychiatric disorders, the efficiency of drug treatment is far from optimal. Regardless of the initial choice and dose of standard psychiatric medication, about 30-50% of patients will not respond sufficiently to acute treatment while others suffer from severe adverse drug reactions. The patient-to-patient differences in drug response can be explained on the basis of variability in drug pharmacokinetic and pharmacodynamic processes. The involvement of the human polycyclic aromatic hydrocarbon (PAH)-inducible CYP1A2 in the metabolism of several psychotropic drugs is increasingly acknowledged. Currently, it is well-known that this enzyme shows a wide interindividual variability, but controversy has long surrounded the issue of a polymorphic distribution of the enzyme activity leading to pronounced differences in drug response. Moreover, whether genetic polymorphism and/or environmental factors play a definitive role has not yet unequivocally established. On the other hand, combination pharmacotherapy is commonly used in clinical psychiatry, and the CYP1A2 enzyme is the target of many clinically relevant drug interactions.This review is dealing with factors that could better explain patient-to-patient differences in drug response to psychotropic drugs, including CYP1A2 genetic polymorphisms, environmental factors as well drug interactions modulating the CYP1A2 enzyme activity.

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Interaction of olanzapine with fluvoxamine

Cited by 29 publications

References 1 publication

Low-Dose Fluvoxamine as an Adjunct to Reduce Olanzapine Therapeutic Dose Requirements

Low-Dose Fluvoxamine as an Adjunct to Reduce Olanzapine Therapeutic Dose Requirements

Clinically relevant interactions between newer antidepressants and second-generation antipsychotics

Pharmacogenetics of Cytochrome P450 (CYP) 1A2 and Variability in Psychotropic Drug Response

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