Clozapine guidelines:

Italicized guidelines are specific to CRH

-Physician must be registered with REMS
-Patient has failed other antipsychotics and or symptoms are severe enough to clinically
warrant trial. Patient meets DSM 5 criteria for psychotic illness or has behaviors that can
be targeted by Clozaril such as aggression and / or SIB
-Patient or guardian has signed clozaril paper consent and the Clozapine Committee has
approved patient for treatment
-Before initiation patient has gets:
1. CBC with diff (monitoring for Agranulocytosis)
2. CMP (monitoring for any metabolite abnormalities that could increase seizure
risk)
3. Fasting lipids
4. HgA1c
5. Weight
6. Myocarditis panel including high sensitivity CRP
7. EKG
Monitoring for metabolic syndrome
-Start patient at 12.5mg and increase as tolerated
-If patient misses doses for more than 48hrs he or she is restarted at 12.5mg and clock
goes back to 0.
-Monitoring
1. CBC with diff q weekly for 6 months then CBC biweekly for 6 months and then q
monthly thereafter
2. Myocarditis panel for 4 weeks after initiation
3. EKG for 4 weeks after initiation
4. Q weekly weights
5. Myocarditis Symptoms Progress Note for Patients on Clozapine for 4 weeks after
initiation
Actions to be taken when the monitoring of symptoms, signs or tests raises a
concern for clozapine related myocarditis are summarized in these tables:
Table 1:
Monitoring
Decisions by
ANC Level
Normal Range for a New Patient
GENERAL POPULATION

ANC 1500/L

BEN POPULATION

ANC 1000/L
Obtain at least two
baseline ANC levels
before initiating treatment

Clinical

Actions

Acute myocarditis Stop clozapine,

identified orRecommendation
Monitor on
Treatment
strongly suspected MPU and
obtain a

Initiate treatment
2D Echo.
Troponin
If treatment
> interrupted:
2X
30 limits
days, continue monitoring as before
upper
30 days, monitor as if new patient
Cardiology
normal
consult, if

Discontinuation for reasons

other than
clinically
neutropenia
indicated
hs-CRP > 100

Recommended
Frequency and Clinical
ANC Level
ANC Monitoring

Weekly from initiation to six months

Every 2 weeks from 6 to 12 months
Monthly after 12 months

See section 2.4 of the full prescribing

information

Mild Neutropenia
(1000 1499/L)*

GENERAL POPULATION

Continue treatment

BEN POPULATION

Moderate Neutropenia
(500 999/L)*

Severe Neutropenia
( 500/L)*

Discontinuation for reasons other than

neutropenia

See section 2.4 of the full Prescribing

Information

Recommend hematology consultation

Interrupt treatment for suspected clozapine
induced neutropenia
Resume treatment once ANC normalizes
to 1000/L

Recommend hematology consultation

Continue treatment

Recommend hematology consultation

Interrupt treatment for suspected clozapine
induced neutropenia
Do not rechallenge unless prescriber
determines benefits outweighs risks

BEN POPLATION

BEN POPULATION
Weekly from initiation to six months
Every 2 weeks from 6 to 12 months
Monthly after 12 months

GENERAL POPULATION

Three times weekly until ANC 1500/L

Once ANC 1500/L return to patients
last Normal Range ANC monitoring
interval

BEN POPULATION

Mild neutropenia is normal range for BEN

population, continue treatment
Obtain at least two baseline ANC levels
before initiating treatment
It treatment interrupted
30 days, continue monitoring as before
30 days, monitor as if new patient

GENERAL POPULATION

GENERAL POPULATION

Recommend hematology consultation

Interrupt treatment for suspected clozapine
induced neutropenia
Do not rechallenge unless prescriber
determines benefits outweighs risks

GENERAL POPULATION

Daily until ANC 1000L, then

Three times weekly until ANC 1500L
Once ANC 1500/L check ANC weekly
for 4 weeks, then return to patients last
Normal Range ANC monitoring
interval**

BEN POPULATION

Three times weekly until ANC 1000/L

or patients known baseline
Once ANC 1000/L or patients known
baseline, check ANC weekly for 4 weeks,
then return to patients last Normal BEN
Range ANC monitoring interval**

GENERAL POPULATION

Daily until ANC 1000/L

Three times weekly until ANC 1500/L
If patient rechallenged, resume treatment
as a new patient under Normal Range
monitoring once ANC 1500/L

BEN POPULATION

Daily until ANC 500/L

Three times weekly until ANC patients
established baseline
If patient rechallenged, resume treatment
as a new patient under Normal Range
monitoring once ANC 1000/L or at
patients baseline

* Confirm all initial reports of ANC less than 1500L (ANC < 1000/L for BEN patients) with a repeat ANC measurement within 24 hours
** If clinically appropriate

Table 2: Recommendations for Monitoring After Discontinuation of Clozapine

Moderate Neutropenia
(500 to 999/L)*

GENERAL POPULATION

Daily until ANC 1000L, then

Three times weekly until ANC 1500/L

Severe Neutropenia
(less than 500/L)*

GENERAL POPULATION

Daily until ANC 1000/L, then

Three times weekly until ANC 1500L

BEN POPULATION

Daily until ANC 500/L

Three times weekly until ANC patients established baseline

* Confirm all initial reports of ANC less than 1500 L (ANC < 1000/L for BEN patients) with a repeat ANC measurement within 24 hours