White Blood Cell (WBC) Monitoring

Patients who have never received treatment with any clozapine formulation will be monitored according to the schedule detailed in Table 1 below. During the first 6 months of FazaClo treatment, WBC count and ANC test results must be monitored on a weekly basis. If the WBC count does not fall below 3500/mm3 and ANC below 2000/mm3 during the first 6 months of treatment, the frequency of monitoring can be decreased to once every 2 weeks for the next 6 months. If the WBC count does not fall below 3500/mm3 and ANC below 2000/mm3 during the next 6 months of treatment, the frequency of monitoring can be decreased to once every 4 weeks, thereafter, ad infinitum.

Completed WBC and ANC test results and corresponding dates of blood draws and treatment dispensation information will be submitted on WBC count and ANC Monitoring Forms (Click here to obtain a WBC count and ANC Monitoring Form) by the pharmacists to the FazaClo^® Patient Registry according to the data submission timeline outlined below.

Patients CONTINUING on Clozapine Treatment

Patients who are currently receiving treatment with another formulation of clozapine and are switched to FazaClo treatment will be monitored according to the schedule detailed in Table 1 below.. During the first 6 months of clozapine treatment (including time on prior clozapine treatment as well as current treatment with FazaClo), blood test results must be monitored on a weekly basis. If the WBC count does not fall below 3500/mm3 and the ANC below 2000/mm3 during the first 6 months of combined treatment with all formulations of clozapine, the frequency of monitoring can be decreased to once every 2 weeks for the next 6 months. Following the first 6 months and after a total of 12 months of treatment (including time on prior clozapine treatment as well as current treatment with FazaClo), if the WBC count does not fall below 3500/mm3 and the ANC below 2000/mm3, the frequency of monitoring can be decreased to once every 4 weeks, thereafter, ad infinitum.

Completed WBC count and ANC Monitoring Forms (Click here to obtain a WBC count and ANC Monitoring Form) including WBC and ANC test results and corresponding dates of blood draws and treatment dispensation information will be submitted by pharmacists to the FazaClo Patient Registry according to the data submission timeline outlined below.

Table 1: Frequency of Monitoring Based on Stage of Therapy or Results from WBC Count and ANC Monitoring Tests

Situation	Hematological Values for Monitoring	Frequency of WBC and ANC Monitoring
Initiation of therapy	WBC ≥3500/mm³ ANC ≥2000/mm³ Note: Do not initiate in patients with (1) history of myeloproliferative disorder or (2) clozapine-induced agranulocytosis or granulocytopenia.	Weekly for 6 months
6-12 months of therapy	All results for WBC ≥3500/mm³ and ANC ≥2000/mm³	Every 2 weeks for 6 months
12 months of therapy	All results for WBC ≥3500/mm³ and ANC ≥2000/mm³	Every 4 weeks ad infinitum
Immature forms present	N/A	Repeat WBC and ANC
Discontinuation of Therapy	N/A	Weekly for at least 4 weeks from day of discontinuation or until WBC ≥ 3500/mm³ and ANC ≥ 2000/mm³
Substantial drop in WBC or ANC	Single drop or cumulative drop within 3 weeks of WBC ≥3000/mm³ or ANC ≥1500/mm³	1. Repeat WBC and ANC 2. If repeat values are 3000/mm³ ≤ WBC≤ 3500/mm³ and ANC > 2000/mm³, then monitor twice weekly
Mild leukopenia Mild granulocytopenia	3500/mm³>WBC≥3000/mm³ and/or 2000/mm³>ANC≥1500/mm³	Twice-weekly until WBC >3500/mm³ and ANC >2000/mm³ then return to previous monitoring frequency
Moderate leukopenia Moderate granulocytopenia	3000/mm³>WBC≥2000/mm³ and/or 1500/mm³>ANC≥1000/mm³	1. Interrupt therapy 2. Daily until WBC > 3000/mm³ and ANC >1500/mm³ 3. Twice-weekly until WBC > 3500/mm³ and ANC > 2000/mm³ 4. May rechallenge when WBC > 3500/mm³ and ANC > 2000/mm³ 5. If rechallenged, monitor weekly for 1 year before returning to the usual monitoring schedule of every 2 weeks for 6 months and then every 4 weeks ad infinitum
Severe leukopenia Severe granulocytopenia	WBC <2000/mm³ and/or ANC <1000/mm³	1. Discontinue treatment and do not rechallenge patient 2. Monitor until normal and for at least four weeks from the 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
Agranulocytosis	ANC <500/mm³	1. Discontinue treatment and do not rechallenge patient 2. Monitor until normal but for at least four weeks from the 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
WBC = White blood cell count ANC = Absolute neutrophil count

Patients Experiencing a BREAK on Clozapine Treatment

Patients whose treatment with a formulation of clozapine other than FazaClo has been interrupted will be monitored according to the schedule detailed in Table 2 below. The schedules for patients who were on FazaClo or another clozapine treatment for less than 6 months prior to the treatment break, for patients who were on FazaClo or another clozapine treatment for 6 12 months, and for patients on FazaClo or another clozapine for 12 months or longer are presented in sections I, II, and III, respectively. The monitoring schedule will depend on the time patients were on clozapine prior to treatment interruption, the length of the interruption, and the blood-event status. An abnormal blood event is defined as a WBC count below 3500/mm³ or ANC below 2000/mm^3.

Table 2: Monitoring Schedule: Patients Experiencing BREAK in Clozapine Therapy

Section I—Patients on therapy for less than 6 months who have experienced a break in therapy

Duration of therapy break from clozapine	Blood events	Frequency of WBC count and ANC monitoring
3 Days to ≤ 1 month	No Abnormal	Weekly WBC count and ANC monitoring for up to 6 months of therapy, then may reduce to every 2 weeks for the next 6 months, and, to every 4 weeks indefinitely after 12 months of use. If all WBC counts ≥3500/mm³ and all ANCs ≥2000/mm³, transition to reduce frequency of monitoring is permitted.
>1 month	No Abnormal	Must restart 6-month period of weekly WBC count and ANC monitoring at Day 0.
ANY	Abnormal (but patient remains rechallengeable)*	If WBC count between ≥3000/mm³ and <3500/mm³ and/or ANC falls between ≥1500/mm³ and <2000/mm³ then twice-weekly. Once values return to WBC count >3500/mm³ and ANC >2000/mm³, resume previous monitoring frequency. However, if WBC count between ≥2000/mm³ and <3000/mm³ and/or ANC between ≥1000/mm³ and <1500/mm³, interrupt therapy, daily WBC and ANC monitoring until WBC >3000/mm³ and ANC >1500 /mm³, then once values return to WBC count >3500/mm³ and ANC >2000/mm³ may rechallenge with monitoring of WBC count and ANC weekly for 1 year before returning to previous monitoring schedule.

Section II - Patients on therapy for 6 to 12 months who have experienced a break in therapy

Duration of therapy break from clozapine	Blood events	Frequency of WBC count and ANC monitoring
3 Days to ≤1 month	No Abnormal	Weekly WBC count and ANC monitoring for 6 weeks, then may reduce to every 2 weeks for the next 6 months. If all WBC counts ≥3500/mm³ and ANCs ≥2000/mm³, transition to reduce frequency of monitoring is permitted.
>1 month	No Abnormal	Weekly WBC count and ANC monitoring for 6 months of therapy, then may reduce to every 2 weeks for the next 6 months. If all WBC counts ≥3500/mm³ and ANCs ≥2000/mm³, transition to reduce frequency of monitoring is permitted.
ANY	Abnormal (but patient remains rechallengeable)*	If WBC count falls between ≥3000/mm³ and <3500/mm³ and/or ANC falls between ≥1500/mm³ and <2000/mm³ then twice-weekly. Once values return to WBC count >3500/mm³ and ANC >2000/mm³, resume previous monitoring frequency. However, if WBC count between ≥2000/mm³ and <3000/mm³ and/or ANC between ≥1000/mm³ and <1500/mm³, interrupt therapy, daily WBC and ANC monitoring until WBC >3000/mm³ and ANC >1500/mm³ then once values return to WBC count >3500/mm³ and ANC >2000/mm³ may rechallenge with monitoring of WBC count and ANC weekly for 1 year before returning to previous monitoring schedule.

Section III - Patients on therapy for greater than 12 months who have experienced a break in therapy

Duration of therapy break from clozapine	Blood events	Frequency of WBC count and ANC monitoring
3 Days to ≤1 month	No Abnormal	Weekly WBC count and ANC monitoring for 6 weeks, then return to monitoring every 4 weeks. If all WBC counts ≥3500/mm³ and ANCs ≥2000/mm³ transition to reduce frequency of monitoring is permitted.
>1 month	No Abnormal	Weekly WBC count and ANC monitoring for 6 months of therapy, then may reduce to every 2 weeks for the next 6 months, and, finally, return to every 4 weeks after 12 months of use. If all WBC counts >3500/mm³ and ANCs ≥2000/mm³ transition to reduce frequency of monitoring is permitted.
ANY	Abnormal (but patient remains rechallengeable)*	If WBC count between ≥3000/mm³ and <3500/mm³ and/or ANC falls between ≥1500/mm³ and <2000/mm³ then twice weekly. Once values return to WBC count >3500/mm³ and ANC >2000/mm³, resume previous monitoring frequency. However, if WBC count between ≥2000/mm³ and <3000/mm³ and/or ANC between ≥1000/mm³ and <1500/mm³, then once values return to WBC count >3500/mm³ and ANC >2000/mm³ may rechallenge with monitoring of WBC count and ANC weekly for 1 year before returning to previous monitoring schedule.

*Patients can be rechallenged with FazaClo if all WBC counts are above 2000/mm³ and all ANCs are above 1000/mm³.

Patients eligible for FazaClo fall into one of the following categories:

NEW - A patient who has never received treatment with any clozapine formulation

CONTINUING - A patient who is currently receiving treatment with a formulation of clozapine other than FazaClo.

INTERRUPTED THERAPY (BREAK) - A patient whose treatment with a formulation of clozapine other than the FazaClo formulation has been temporarily discontinued or interrupted due to an abnormal blood level as defined by clozapine labeling or another reason not due to an abnormal blood level.

Patients not eligible for FazaClo fall into the following category:

PERMANENTLY DISCONTINUED - patient whose treatment with FazaClo or another formulation of clozapine other than FazaClo has been permanently discontinued because they meet non-rechallenge criteria (WBC count <2000/mm3 and/or ANC <1000/mm3) and are listed in the Clozapine National Non-Rechallenge Masterfile (such patients are at risk for developing agranulocytosis and should never be rechallenged with any clozapine product).

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