Clozapine
Clozaril
Second Generation Anti-Psychotic
› Treatment Resistant
Schizophrenia/Schizoaffective
– Not 1st line due to SE
– Must fail 2 antipsychotics (2 atypical
or 1 atypical and 1 typical) first
› Oral dosing only
– Tablets
– ODT
– Oral Suspension
Clozapine Pharmacodynamic Profile
PHARMACOKINETIC
PROPERTIES
Cytochrome P450 Pathways
(hepatically metabolized)
CYP3A4
CYP1A2
Tobacco users may
need to double dose
related to 1A2
induction
Half-Life
12 hour=BID dosing
The Good
› Most effective treatment for refractory schizophrenia
– Miracle drug for some
– Lower rehospitalization rates WITH compliance
› Reduces risk of suicide
› Does not cause EPS
– Improves tardive dyskinesia
The Bad
› Severe constipation/GI hypomotility
– Paralytic Ileus
– Avoid opioids, iron, anticholinergics
› Hypersalivation
– Muscarinic cholinergic receptor antagonism
› Metabolic Disorder
– Weight gain, dyslipidemia, insulin resistance
› Orthostasis
– Alpha 1 adrenergic antagonist
› Sedation/Drowsiness
– Histamine 1 antagonist
– Avoid Benzos and anticholinergics
› Myocarditis
Side Effects
The Ugly
CLOZAPINE REMS
Monitoring guidelines
BENIGN ETHNIC
NEUTROPENIA
MONITORING
Before you Start
Weight, BMI, waist circumference, VS
Family history
Diabetes, HTN, CVD, dyslipidemia
Baseline labs
Troponin, CRP, Fasting lipids and A1C, CMP, CBC, thyroid
Baseline EKG
Smoking status (may require double the dose)
Register your patient in REMS
The Bottom Line
Clozapine works for treatment resistant schizophrenia BUT also requires extensive
monitoring, so compliance is a huge factor here. Know your patient. If your patient has a
history of non-medication compliance, they aren’t a good candidate unless they are in an
inpatient setting, a 24-hour care setting such as a BHRF, or incarcerated.