Saturday, April 15, 2006

New Clozaril Monitoring Requirements

A requirement for absolute neutrophil count (ANC) has been added to the baseline requirements for clozapine therapy; patients must have both WBC and ANC in the normal range (3500/mm3 and 2000/mm3 or greater, respectively). ANC must be determined and reported along with each WBC.
A monthly monitoring schedule may only be initiated after 1 year (6 months weekly, 6 months every 2 weeks) of WBCs and ANCs in the normal range.
Because of the increased risk for agranulocytosis in patients rechallenged with clozapine after recovery from an initial episode of moderate leukopenia (WBC range, <3000/mm3 and 2000/mm3 or higher, and/or ANC range, <1500/mm3 and 1000/mm3 or higher), these patients now require weekly monitoring of WBC and ANC for a period of 12 months.
Complete information regarding changes in monitoring frequency after interruption of therapy is available at:
For patients whose WBC is currently being monitored on a weekly or biweekly basis according to the previous schedule, ANC reporting is required from this point on. Patients may continue on their monitoring schedule and 6-month transition to biweekly or monthly monitoring if WBC and ANC remain in the normal range.
Healthcare providers are required to submit all WBC and ANC values to the Clozaril National Registry during treatment and until values reach the normal range after discontinuation of clozapine in nonrechallengeable patients (WBC, <2000/mm3 and/or ANC, <1000/mm3).
The FDA also warned of the increased risk for death associated with off-label use of clozapine in elderly patients with dementia-related psychosis.
The warning was based on an analysis of data from 17 placebo-controlled, 10-week trials showing that use of olanzapine, aripiprazole, risperidone, and quetiapine in 5106 elderly patients with dementia-related behavioral disorders was associated with an increased risk for mortality compared with placebo (4.5% vs 2.6%).
Because the 1.6- to 1.7-fold increase in death risk was linked to medications from all 3 classes of atypical antipsychotic medications, it is considered by the FDA to be a class effect.
In addition, the FDA advised that use of clozapine is now contraindicated in patients with paralytic ileus, a condition previously listed as a potential adverse event in the labeling. The change was based on a review and evaluation of data from global postmarketing safety and clinical trial databases.
The postmarketing safety database also included reports of hypercholesterolemia and/or hypertriglyceridemia in patients receiving clozapine. Moreover, database and literature data indicate that concomitant use of citalopram results in significantly increased clozapine blood concentrations, potentially resulting in adverse effects.
Clozapine is indicated for the treatment of severely ill patients with schizophrenic who fail to respond adequately to standard therapy and for reducing the risk for recurrent suicidal behavior in at-risk patients with schizophrenia or schizoaffective disorder.

The above is taken from
I hadn't heard of the citalopram (Celexa)-clozapine drug interaction before.
A quick Pub Med search reveals these 2 relevant articles:
Int Clin Psychopharmacol. 1998 Jan;13(1):19-21.
Co-administration of citalopram and clozapine: effect on plasma clozapine levels.
Taylor D, Ellison Z, Ementon Shaw L, Wickham H, Murray R
.Bethlem & Maudsley NHS Trust, London, UK.Antidepressants are frequently used in the treatment of depressive symptoms associated with schizophrenia. In patients taking clozapine, choice of antidepressant is complicated by additive pharmacodynamic effects and by pharmacokinetic interactions. We predicted that citalopram would not elevate plasma clozapine levels when the two drugs were co-administered because it does not inhibit the relevant enzyme systems. In this preliminary study of five patients given citalopram and clozapine there was no overall change in mean clozapine levels. Based on this limited evidence, citalopram might be the antidepressant of choice in patients taking clozapine.
J Clin Psychiatry. 2000 Apr;61(4):301-2.
Citalopram and clozapine: potential drug interaction.
Borba CP, Henderson DC.Publication Types:
Case Reports
No abstract available.
Does anyone have anymore info about the Celexa/Clozaril drug interaction???

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