Olanzapine fluvoxamine

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

Olanzapine 1A2 2D6 Fluvoxamine, ciprofloxacin, paroxetine Cigarette smoking... 

CYP1A2 TCAs, clozapine, haloperidol, fluvoxamine, mirtazepine, olanzapine... 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

Bogetto, F, Bellino, S., Vaschetto, P., and Ziero, S. (2000) Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD) a 12-week open trial. Psychiatry Res 96 91-98. 

FIGURE 11-44. Clozapine and olanzapine are substrates for cytochrome P450 1A2 (CYP450 1A2). When these drugs are given with an inhibitor of this enzyme, such as the antidepressant fluvoxamine, plasma levels of olanzapine and clozapine can rise. 

Olanzapine is metabolized by CYP1A2, and fluvoxamine, which inhibits CYP1A2, increases plasma olanzapine concentrations (SEDA-24, 71). 

A 21-year-old woman had a very high olanzapine plasma concentration (120 ng/ml) during co-adminis-tration of fluvoxamine 150 mg/day and olanzapine 15 mg/day her symptoms included slight tremor, rigid movements, and general discomfort (113). 

Of the SSRIs, fluvoxamine is the most potent inhibitor of CYP1A2 and is therefore likely to increase plasma olanzapine concentrations. The extrapyramidal effects in this case were presumably due to excessive blockade of dopamine D2 receptors by raised olanzapine concentrations. 

Fluvoxamine increases clozapine plasma concentrations (SEDA-27, 58). and the differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine have been studied in healthy volunteers (256). Fluvoxamine significantly reduced the N-des-methylclozapine to clozapine ratio, implying reduced metabolism of clozapine. 

In 23 patients with obsessive-compulsive disorder who had not responded to a 6-month course of fluvoxamine (300 mg/day), olanzapine (5 mg/day) was added in an open comparison (28). There was a significant reduction in the mean score on the Yale-Brown Obsessive-Compulsive Scale concomitant schizotypal personality disorder was the only factor significantly associated with a response. The most common adverse effects were mild to moderate weight gain and sedation. 

Fluvoxamine under steady-state conditions increases the systemic availability of olanzapine and inhibits the metabolism of clozapine, as shown in 21 male non-smoking Chinese volunteers (mean age 27 years) (277). This could be related to the different metabolic pathways and secretion rates of the two drugs it would be advisable to reduce the dosage of olanzapine and to extend the dosing interval of clozapine when they are combined with fluvoxamine. 

Albers LJ, Ozdemir V, Marder SR, Raggi MA, Aravagiri M, Endrenyi L, Reist C. Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose requirements a prospective dose-adjusted drug interaction strategy. J Clin Psychopharmacol 2005 25 170-4. 

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