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CLOZARIL: Starting a Patient
1. Call the CLOZARIL National Registry (CNR) to obtain a rechallenge number and to confirm that you and your pharmacy are registered.
2. Obtain a baseline WBC with ANC from patient. If within normal limits, WBC ≥ 3500/mm3, ANC ≥ 2000/mm3, prescribe CLOZARIL tablets.
3. Submit WBC and ANC information to the registered pharmacy.
4. Please be prepared to provide your DEA # to the CNR when you are registered for the first time.
For forms, patient enrollment, or medical information call the CLOZARIL National Registry:
Recommended CLOZARIL® (clozapine) dosage titration at start of therapy1
Total (mg)
Total (mg)
*Optional Subsequent dosage increments should be made no more than once or twice weekly, in increments not to exceed 100 mg. CLOZARIL: Managing the Patient
Current Monitoring Frequency
Eligibility for Monthly Monitoring
Every 2 weeks (biweekly) for 6 continuous months, following 6 continuous months of weekly
YES. Only if all WBC counts ≥ 3000/mm3 (and ANC ≥1500/mm3 if reported)
Every 2 weeks or weekly. Therapy interrupted after May 12, 2005, due to moderate leukopenia
NO. Only after 1 year of continuous weekly monitoring and then 6 months of continuous every two
and/or granulocytopenia*, with consecutive monitoring since restart (rechallenge) of therapy. weeks monitoring from the date of restart (rechallenge) with all WBC/ANC above increased monitoring frequency values***. Weekly therapy for ≤6 months
NO. Patient must have 6 continuous months of weekly monitoring, followed by 6 months of continuous
monitoring every two weeks with all WBC/ANC above increased monitoring frequency values**.
Weekly therapy for ≥6 continuous months, but never monitored biweekly.
NO. Patient must have 6 continuous months of monitoring every two weeks with all WBC/ANC above
increased monitoring frequency values**.
Increased Monitoring Frequency Requirements
Patient is currently monitored monthly and experiences a WBC < 3500/mm3 and/or an ANC Monitoring should be done twice weekly until WBC/ANC values are ≥3500 and ≥ 2000, respectively. The patient can return to monthly blood work. Patient is currently monitored every 2 weeks and experiences a WBC < 3500/mm3 and/or an ANC Monitoring should be done twice weekly until WBC/ANC values are ≥3500 and ≥2000, respectively. The patient should then be monitored every two weeks for 6 continuous months before progressing to monthly blood work. Patient is currently monitored weekly and experiences a WBC < 3500/mm3 and/or an ANC Monitoring should be done twice weekly until WBC/ANC values are ≥3500 and ≥2000, respectively. The patient should then be monitored weekly for 6 continuous months before progressing to every twoweeks, and then monthly, blood work. **Prior to May 12, 2005 values for WBC and ANC counts requiring interruption of therapy were WBC ≤ 3000/mm3 and/or ANC ≤ 1500/mm3. After May 12, 2005 values for counts requiring increased monitoring frequency of therapyare WBC ≤ 3500/ mm3 and/or ANC ≤ 2000mm3, respectively.
Following discontinuation of therapy for any reason, the patient should have WBC and ANC count monitoring once a week for a minimum of 4 weeks. If at the end of 4 weeks WBC < 3500/mm3 and/or ANC < 2000/mm3, weeklymonitoring should continue until WBC ≥3500/mm3 and ANC ≥ 2000/mm3. Clozaril (clozapine) use is associated with a substantial risk of seizure, affected 1% to 2% of patients at low doses (below 300 mg/day), 3% to 4% at moderate doses (300 mg/day to600 mg/day), and 5% at high doses (600 mg/day to 900 mg/day). Clozaril is contraindicated in patients with paralytic ileus. In clinical trials, Clozaril was associated with a 1% to 2%incidence of agranulocytosis, a potentially fatal blood disorder, which, if caught early, can be reversed. Mandatory monitoring of WBC counts and ANC's and drug dispensing as perthe requirements specified in the package insert, provide an efficient means of determining developing agranulocytosis. Analysis of post-marketing safety databases suggests thatClozaril is associated with an increased risk of fatal myocarditis, especially during, but not limited to, the first month of therapy. Orthostatic hypotension may occur in some patients,especially during the initial phases of treatment, and can, in rare cases (approximate incidence of 1/3000), be accompanied by collapse and/or cardiac arrest. Analysis of clinicalstudies reveal that elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Patients with anestablished diagnosis of diabetes mellitus who are started on CLOZARIL should be monitored regularly for worsening glucose control (e.g., polydipsia, polyuria, polyphagia, and weakness).
Table 1. Frequency of Monitoring based on Stage of Therapy or Results from WBC and ANC Monitoring Tests
Situation
Hematological Values for Monitoring
Frequency of WBC and ANC Monitoring
Note: Do not initiate in patients with 1) history of myeloproliferative disorder or 2) Clozaril® (clozapine)induced agranulocytosis or granulocytopenia Weekly for at least 4 weeks from day of discontinuation or until WBC ≥3500/mm3 and ANC >2000/mm3 Single Drop or cumulative drop within 3 weeks 2. If repeat values are 3000/mm3 ≤WBC ≤3500/mm3 and ANC <2000/mm3, then monitor twice weekly Twice-weekly until WBC >3500/mm3 and ANC >2000/mm3 then return to previous monitoring frequency 2. Daily until WBC count >3000/mm3 and ANC >1500/mm3 3. Twice weekly until WBC >3500/mm3 and ANC >2000/mm34. May rechallenge when WBC >3500/mm3 ANC >2000/mm35. If rechallenged, monitor weekly for 1 year before returning to the usual monitoring schedule of every 2 weeks for6 months and then every 4 weeks ad infinitum.
1. Discontinue treatment and do not rechallenge patient.
2. Monitor until normal and for at least four weeks from day of discontinuation as follows:• Daily until WBC >3000/mm3 and ANC >1500/mm3• Twice weekly until WBC >3500/mm3 and ANC >2000/mm3• Weekly after WBC >3500/mm3 1. Discontinue treatment and do not rechallenge patient.
2. Monitor until normal and for at least four weeks from day of discontinuation as follows:• Daily until WBC count >3000/mm3 and ANC >1500/mm3• Twice weekly until WBC >3500/mm3 and ANC >2000/mm3• Weekly after WBC >3500/mm3 *WBC=white blood cell count; ANC=absolute neutrophil count Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936

Source: http://www.clozaril.com/hcp/tools/pdf/CLOZARIL_dosing_guide.pdf