Home  >  News  >  January 18

New warnings about Clozaril (clozapine)

January 18, 2006 - Novartis and the FDA notified healthcare professionals of revisions to the BOXED WARNING, WARNINGS, CONTRAINDICATIONS, PRECAUTIONS and ADVERSE REACTIONS sections of the prescribing information (PI) for Clozaril (clozapine) tablets.

Recommendations from the FDA's Psychopharmacological Drugs Advisory Committee regarding the white blood cell monitoring schedule, required for all clozapine users, has resulted in modification in the monitoring schedule. Additional labeling changes address safety issues related to dementia-related psychosis, parlytic ileus, hypercholesterolemia and pharmacokinetic interaction with citalopram.

Changes in the white blood cell monitoring schedule are listed below.

  • Requirement that the absolute neutrophil count (ANC) be determined and reported along with each WBC count.
  • New parameters for initiation of Clozaril treatment: WBC > 3500/mm3 and ANC > 2000/mm3.
  • Initiation of monthly monitoring schedule after one year (six months weekly, six months every two weeks) of WBC counts and ANCs in the normal range (WBC > 3500/mm3 and ANC > 2000/mm3).
  • Addition of cautionary language to prescribers describing the increased risk of agranulocytosis in patients who are rechallenged with clozapine following recovery from an initial episode of moderate leukopenia(3000/mm3 > WBC > 2000/mm3 and/or 1500/mm3 >ANC >1000/mm3). After recovering from such an episode, these patients are now required to undergo weekly monitoring for 12 months if they are re-challenged.
Recently, the FDA reviewed data related to the use of atypical antipsychotics for the treatment of behavioral symptoms in elderly patients with dementia. They have concluded that the labeling for all atypical antipsychotics should be updated to include information about an increased risk of mortality in elderly patients with dementia-related psychosis.

Paralytic ileus has been a listed adverse event associated with Clozaril use as reflected in both the PRECAUTION and ADVERSE REACTIONS sections of the PI. However, based on a review and evaluation of the global post-marketing safety and clinical trial databases for Clozaril, Novartis has concluded that paralytic ileus should be listed as a contraindication in PI.

Based on data from the global post-marketing safety database, the ADVERSE REACTIONS (Post-Marketing Clinical Experience) section of the PI was revised to reflect reports of hypercholesterolemia and/or hypertriglyceridemia associated with Clozaril treatment.

Following a review of the data from the medical literature as well as data from our global post-marketing safety database, the FDA and Novartis have determined that the conconmitant use of Clozaril and citalopram results in clinically significant elevations of Clozaril blood concentrations. Consequently, the PRECAUTIONS (Pharmacokinetic-Related Interactions) section of the PI was revised to include citalopram.

Patients taking Clozaril or clozapine should NOT discontinue taking their medication before speaking with their physician.

Questions or concerns regarding this important safety information can be directed to Novartis medical department at 1-800-NowNovartis. As always, pharmacies and members can also contact the RxAmerica customer service desk at 1-800-770-8014 if they have any questions about this new product warning.