NORTHPOINTE BEHAVIORAL HEALTHCARE SYSTEMS
POLICY TITLE: Clozaril / Clozapine
MANUAL: Health
ORIGINAL EFFECTIVE DATE: 4/1/03
REVIEWED/REVISED ON DATE: 11/28/12
REVISIONS TO POLICY STATEMENT:
YES
PAGE 1 of 4
SECTION: Medication
BOARD APPROVAL DATE: 7/25/13
CURRENT EFFECTIVE DATE: 12/3/12
NO
OTHER REVISIONS:
YES
NO
APPLICATION:
The policy applies to all Northpointe medical and nursing staff.
POLICY:
It is the policy of Northpointe Behavioral Healthcare Systems to establish and follow guidelines for the use and
monitoring of Clozaril/Clozapine.
1.
2.
3.
4.
Only those individuals who have a substantiated thought disorder, psychosis or a bipolar disorder that is
refractory to other treatment shall be considered for treatment with Clozaril.
Clozaril shall not be the first line of treatment and should only be prescribed when other antipsychotic
agents have been tried at a sufficient dose and for a sufficient duration of time.
The individual who is a candidate for Clozaril shall be compliant with current medication regime.
The individual in need of an antipsychotic agent, and presents with chronic abnormal movements may also
be a candidate for Clozaril.
PURPOSE:
The purpose of the procedure is to establish guidelines for the use of Clozaril and to describe the monitoring process.
PROCEDURE:
Registering a New Individual:
Physicians and psychiatric nurse practitioners who prescribe Clozapine and pharmacies who dispense it must be
registered. The prescriber’s and pharmacy’s name and/or DEA number will be needed when registering an individual
Prior to being registered the individual must have a WBC of 3500/mm3 or greater and an ANC of 2000/mm3 or
greater. A new individual must be registered with the appropriate Clozaril Registry. Eligibility is confirmed by the
pharmacy.
Transferring a Consumer:
An individual must be re-challenged or re-registered each time the prescriber or pharmacy changes, or in the event
that the individual’s name changes.
Monitoring:
The prescribing practitioner and the nurse monitoring the individual should have complete familiarity with Clozaril
(Clozapine) package labeling including warnings about possible sedation, orthostatic hypotension and the risk of
death associated with agranulocytosis. All WBC counts should be promptly reported to the pharmacy for submission
to the appropriate Clozaril Registry. The dispensing of Clozaril is dependent on WBC and ANC results and is limited
to a one-week supply for the first six months. If the WBC is equal to or greater than 3500/mm3 and the ANC is equal
to or greater than 2000/mm3 for the first 6 months of therapy, the prescribing practitioner may change the monitoring
schedule to every other week for an additional 6 months. After 1 full year of stable WBC and ANC results, the
prescribing practitioner may change the monitoring schedule to monthly. See Table 1
NORTHPOINTE BEHAVIORAL HEALTHCARE SYSTEMS
POLICY TITLE: Clozaril / Clozapine
PAGE 2 of 4
MANUAL: Health
SECTION: Medication
ORIGINAL EFFECTIVE DATE: 4/1/03
BOARD APPROVAL DATE: 7/25/13
REVIEWED/REVISED ON DATE: 11/28/12
CURRENT EFFECTIVE DATE: 12/3/12
Table 1: Frequency of Monitoring Based on Stage of Therapy or Results from WBC and ANC Monitoring Tests
Situation
Initiation of therapy
6 months – 12 months of therapy
12 months of therapy
Immature forms present
Discontinuation of Therapy
Substantial drop in WBC or ANC
Mild Leukopenia
----------------Mild Granulocytopenia
Moderate Leukopenia
-----------------Moderate Granulocytopenia
Severe Leukpoenia
---------------Severe Granulocytopenia
Agranulocytosis
Hematological Values for Monitoring
WBC ≥3500/mm3
ANC ≥2000/mm3
Note: Do not initiate in patients with 1) history of
myeloproliferative disorder or 2) Clozaril*
(clozapine) induced agranulocytosis or
granulocytopenia
All results for
WBC ≥3500/mm3 and
ANC ≥2000/mm3
All results for
WBC ≥3500/mm3 and
ANC ≥2000/mm3
N/A
N/A
Frequency of WBC and ANC Monitoring
Weekly for 6 months
Every 2 weeks for 6 months
Every 4 weeks ad infinitum
Repeat WBC and ANC
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 of 1. Repeat WBC and ANC
WBC ≥3000/mm3 or ANC ≥1500/mm3
2. If repeat values are 3000/mm3 ≤WBC
≤ 3500/mm3 and ANC <2000/mm3
then monitor twice weekly.
3500/mm3 > WBC ≥3000/mm3
Twice-weekly until WBC >3500/mm3
-----------and/or-----------and ANC >2000/mm3 then return to previous
3
3
2000/mm > ANC ≥1500/mm
monitoring frequency.
1. Interrupted immediately.
3000/mm3 > WBC ≥2000/mm3
2. Daily until WBC count >3000/mm3 and
-----------and/or-----------ANC >1500/mm3
3
3
1500/mm > ANC ≥1000/mm
3. Twice weekly until WBC >3500/mm3 and
ANC >2000/mm3
4. May rechallenge when WBC >3500/mm3
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.
WBC <2000/mm3
1. Discontinue treatment and do not
-----------and/or-----------rechallenge patient.
ANC <1000/mm3
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
3
1. Discontinue treatment and do not
ANC ≤500/mm
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
NORTHPOINTE BEHAVIORAL HEALTHCARE SYSTEMS
POLICY TITLE: Clozaril / Clozapine
MANUAL: Health
ORIGINAL EFFECTIVE DATE: 4/1/03
REVIEWED/REVISED ON DATE: 11/28/12
PAGE 3 of 4
SECTION: Medication
BOARD APPROVAL DATE: 7/25/13
CURRENT EFFECTIVE DATE: 12/3/12
Induction Dose
Treatment should not be initiated if the WBC count is less than 3500 or if the individual has a history of myeloproliferative
disorder or previous Clozaril induced agranulocytosis or granulocytopenia. The prescribing provider will determine the
dosage of Clozaril on an individual basis in accordance with the degree of mental and/or emotional disturbance being
experienced. Clozaril should be started at the lowest dose possible with gradual increases, while monitoring for toleration
of the medication until a therapeutic end point is met. Titration variances can occur as clinically indicated by the
prescriber.
RECOMMENDED INITIAL CLOZARIL DOSAGE TITRATION GUIDELINE
Week 1
AM (mg)
Hs (mg)
Total (mg)
Week 2
AM (mg)
hs (mg)
Total(mg)
Day 1
12.5
12.5*
12.5 – 25
Day 8
50
100
150
Day 2
25
-----
25
Day 9
100
100
200
Day 3
25
25
50
Day 10
100
100
200
Day 4
25
50
75
Day 11
50
200
250
Day 5
50
50
100
Day 12
50
200
250
Day 6
50
75
125
Day 13
100
200
300
Day 7
50
100
150
Day 14
100
200
300
Therapeutic Range:
Usually a therapeutic range of 300 mg/day to 400 mg/day is efficacious. Because the half-life of Clozaril is 12
hours, the whole dose should not be given all at once. After the dose reaches 300 mg, the dose may be increased
by 50mg in any one day, but no more than 100 mg in any one week. If after several weeks, the degree of
improvement is not acceptable, follow this course of action until a satisfactory result is achieved or the dose
reaches 900 mg (the maximum dose).
Maximum Dose:
Occasionally, individuals may require larger doses to attain maximum therapeutic benefits. In such cases,
judicious weekly or biweekly increments, not to exceed 100 mg are permissible up to a maximum dose of 900
mg/day (maximum single dose of 600 mg). Because of the possibility of increased adverse reactions at higher
doses (in particular seizures) individuals should be given adequate time to respond to a given dosage before
increasing it.
Maintenance Dosing:
After maximum therapeutic benefit has been achieved, many individuals can be maintained effectively at lower
doses. Careful downward titration to the lowest level needed to maintain remission is recommended. Should any
evidence emerge of deterioration in the individual’s condition, the dosage should be increased to the level needed
for maximum benefit and maintained at this level.
Due to the pharmacokinetics profile, the side effect profile, and the elimination half-life, Clozapine is not suited for
prn usage and must not be administered in this fashion.
NORTHPOINTE BEHAVIORAL HEALTHCARE SYSTEMS
POLICY TITLE: Clozaril / Clozapine
MANUAL: Health
ORIGINAL EFFECTIVE DATE: 4/1/03
REVIEWED/REVISED ON DATE: 11/28/12
PAGE 4 of 4
SECTION: Medication
BOARD APPROVAL DATE: 7/25/13
CURRENT EFFECTIVE DATE: 12/3/12
Interrupting Therapy:
There are three instances in which Clozaril therapy may be interrupted:



Noncompliance - individuals forget or run out of medication
Individual develops a WBC count of 2000 to 3000/mm3
Individual develops an Absolute Neutrophil Count (ANC) less than 1000-1500/mm3
Individuals who have been off their Clozaril/Clozapine for 48 hours or more should be re-titrated as deemed
clinically appropriate by prescriber.
Clozaril therapy discontinued for WBC counts below 2000/mm3 or for an ANC less than 1000/mm3 must not be
restarted.
Clozaril therapy interrupted due to an abnormal blood event such as a WBC of 2000-3000/mm3 or an ANC of 10001500/mm3 may be resumed when the WBC > 3500/mm3 and the ANC >2000/mm3. The individual must be reregistered with the Clozaril Registry and will be issued an individual’s clearance code by the Registry when the
eligibility status has been confirmed. This individual must be monitored weekly for one full year before returning to
the usual monitoring schedule of every 2 weeks for 6 months and then every 4 weeks thereafter unless there is an
interruption or treatment break.
Ending Therapy:
In the event of a planned termination of Clozaril therapy, a gradual reduction of 10% of the dose per day over a
period of one to two weeks is recommended. Weekly WBC counts must be done for 4 weeks after Clozaril has
been discontinued or until the WBC >3500/mm and the ANC > 2000/mm.
CROSS REFERENCE:
Psychotropic Medication Use Policy