Frågedatum: 1997-07-21
RELIS database 1997; id.nr. 14105, DRUGLINE
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Does olanzapine interact with perphenazine, nitrazepam, diazepam or clonazepam?/nA middle-aged woma



Fråga: Does olanzapine interact with perphenazine, nitrazepam, diazepam or clonazepam? A middle-aged woman with severe psychosis has previously been successfully treated with clozapin. Due to a low white blood cell count in January clozapin was changed to perphenazine. The cell count is now normalised (mid-March), but the psychosis has deteriorated and treatment with olanzapine (instead of perphenazine) is planned. Other concomitant drugs are nitrazepam, diazepam, and clonazepam.

Sammanfattning: We have found no information concerning drug interactions between olanzapine and perphenazine, nitrazepam or clonazepam. A single dose of olanzapine did not influence the metabolism of diazepam. In the present case, olanzapine in careful dosing and with tapering of the perphenazine treatment, is probably safe. However, the use of a newly approved drug in polytherapy should always be accompanied by close clinical monitoring.

Svar: Olanzapine is an atypical neuroleptic drug, which has recently been approved in Sweden. All of the five drugs mentioned in the question are extensively metabolised by the liver before excretion. According to the manufacturer, olanzapine has little potential in vitro for inhibiting oxidative metabolism of other drugs. A single dose of olanzapine did not influence the kinetics of diazepam (1). The metabolism of olanzapine has been shown to involve two cytochrome P450 enzymes; CYP1A2 and CYP2D6, where CYP1A2 seems to be the most important. The interindividual variance in clearance is large (12-47 L/hr) and is influenced, for example, by smoking (which increases the clearance)(1). Perphenazine metabolism involves CYP2D6. Diazepam is metabolised by CYP2C19. The metabolic pathways of clonazepam and nitrazepam are not fully known.

A Medline search has not revealed any reports concerning olanzapine drug interactions, which was expected given the limited experience with the drug.

Theoretically, olanzapine metabolism may compete with that of perphenazine, possibly leading to increased levels of the latter drug, which is, to be tapered in the present case.

Plasma concentrations of perphenazine and benzodiazepines can be determined at our laboratory (2).

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