Clozaril
(clozapine)
Brand
names:
Clozaril®
FazaClo®
-
Orally
disintegrating tablets: 12.5 mg, 25 mg, 100 mg, 150 mg, 200 mg
Generic
name: clozapine (KLOE
za peen)
Medication
class: Second generation antipsychotic (SGA), atypical antipsychotic
All FDA black box
warnings are at the end of this fact sheet. Please review
before taking this medication.
What
is Clozaril®/FazaClo® and what does it treat?
Clozapine
is a medication that works in the brain to treat schizophrenia. It
is also known as a second generation antipsychotic (SGA) or atypical
antipsychotic. Clozapine
rebalances dopamine and serotonin to improve thinking, mood, and
behavior.
Symptoms
of schizophrenia include:
-
Hallucinations
- imagined voices or images that seem real
-
Delusions
- beliefs that are not true (e.g., other people are reading your
thoughts)
-
Disorganized
thinking or trouble organizing your thoughts and making sense
-
Little
desire to be around other people
-
Trouble
speaking clearly
-
Lack
of motivation
Clozapine
may help some or all of these symptoms.
Clozapine
is also FDA approved to reduce the risk of recurrent suicidal
behavior in people with schizophrenia or schizoaffective disorder.
What
is the most important information I should know about Clozaril®/FazaClo®?
Schizophrenia
requires long-term treatment. Do not stop taking clozapine, even
when you feel better.
Only
your healthcare provider can determine the length of clozapine
treatment that is right for you.
Missing
doses of clozapine may increase your risk for a relapse in your
symptoms.
Do
not stop taking clozapine or change your dose without talking to with
your healthcare provider first.
For
clozapine to work properly, it should be taken everyday as ordered by
your healthcare provider.
Are
there specific concerns about Clozaril®/FazaClo® and
pregnancy?
If
you are planning on becoming pregnant, notify your healthcare
provider to best manage your medications. People living with
schizophrenia who wish to become pregnant face important decisions.
This is a complex decision since untreated schizophrenia has risks to
the fetus, as well as the mother. It is important to discuss the
risks and benefits of treatment with your doctor and caregivers.
Caution
is advised with breastfeeding since clozapine does pass into breast
milk.
What
should I discuss with my healthcare provider before taking Clozaril®/FazaClo®?
-
Symptoms
of your condition that bother you the most
-
If
you have thoughts of suicide or harming yourself
-
Medications
you have taken in the past for your condition, whether they were
effective or caused any adverse effects
-
If
you ever had muscle stiffness, shaking, tardive dyskinesia,
neuroleptic malignant syndrome, or weight gain caused by a
medication
-
If
you experience side effects from your medications, discuss them with
your provider. Some side effects may pass with time, but others may
require changes in the medication.
-
Any
psychiatric or medical problems you have, such as heart rhythm
problems, long QT syndrome, heart attacks, diabetes, high
cholesterol, or seizures
-
If
you have a family history of diabetes or heart disease
-
All
other medications you are currently taking (including over the
counter products, herbal and nutritional supplements) and any
medication allergies you have
-
Other
non-medication treatment you are receiving, such as talk therapy or
substance abuse treatment. Your provider can explain how these
different treatments work with the medication.
-
If
you are pregnant, plan to become pregnant, or are breast-feeding
-
If
you smoke, drink alcohol, or use illegal drugs
How
should I take Clozaril®/FazaClo®?
Clozapine
is usually taken 1 or 2 times per day with or without food.
Typically
patients begin at a low dose of medicine and the dose is increased
slowly over several weeks.
The
dose usually ranges from 25 mg to 700 mg. Only
your healthcare provider can determine the correct dose for you.
Clozapine
orally
disintegrating tablets must remain in their original packaging. Open
the package with clean dry hands before each dose. Do not try to put
tablets in a pillbox if you take the orally disintegrating tablets.
Clozapine
orally
disintegrating tablets will dissolve in your mouth within seconds and
can be swallowed with or without liquid.
Use
a calendar, pillbox, alarm clock, or cell phone alert to help you
remember to take your medication. You may also ask a family
member a friend to remind you or check in with you to be sure you are
taking your medication.
What
happens if I miss a dose of Clozaril®/FazaClo®?
If
you miss a dose of clozapine,
take it as soon
as you remember, unless it is closer to the time of your next dose.
Discuss this with your healthcare provider. Do not double your next
dose or take more than what is prescribed. If you miss more than 2
days of medication, contact your prescriber because he/she may need
to adjust your dose.
What
should I avoid while taking Clozaril®/FazaClo®?
Avoid
drinking alcohol or using illegal drugs while you are taking
clozapine. They may decrease the benefits (e.g. worsen your
confusion) and increase adverse effects (e.g. sedation) of the
medication.
What
happens if I overdose with Clozaril®/FazaClo®?
If
an overdose occurs call your doctor or 911. You may need urgent
medical care. You may also contact the poison control center at
1-800-222-1222.
A
specific treatment to reverse the effects of clozapine does not
exist.
What
are possible side effects of Clozaril®/FazaClo®?
Common
Side Effects
Increased
heart rate, low blood pressure, constipation, increased salivation
Feeling
drowsy or dizzy
Rare
Side Effects
Decreased
white blood cells, inflammation of heart muscle, seizures, severely
low blood pressure, urinary incontinence
Serious
Side Effects
Some
people may develop muscle related side effects while taking
clozapine. The technical terms for these are “extrapyramidal
effects” (EPS) and “tardive dyskinesia” (TD). Symptoms of EPS
include restlessness, tremor, and stiffness. TD symptoms include
slow or jerky movements that one cannot control, often starting in
the mouth with tongue rolling or chewing movements.
Second
generation antipsychotics (SGAs) increase the risk of weight gain,
high blood sugar, and high cholesterol. This is also known as
metabolic syndrome. Your healthcare provider may ask you for a blood
sample to check your cholesterol, blood sugar, and hemoglobin A1c (a
measure of blood sugar over time) while you take this medication.
SGAs
have been linked with higher risk of death, strokes, and transient
ischemic attacks (TIAs) in elderly people with behavior problems due
to dementia.
All
antipsychotics have been associated with the risk of sudden cardiac
death due to an arrhythmia (irregular heart beat). To minimize this
risk, antipsychotic medications should be used in the smallest
effective dose when the benefits outweigh the risks. Your doctor may
order an EKG to monitor for irregular heart beat.
Neuroleptic
malignant syndrome is a rare, life threatening adverse effect of
antipsychotics which occurs in <1% of patients. Symptoms include
confusion, fever, extreme muscle stiffness, and sweating. If any of
these symptoms occur, contact your healthcare provider immediately.
Are
there any risks of taking Clozaril®/FazaClo® for
long periods of time?
Tardive
dyskinesia (TD) is a side effect that develops with prolonged use of
antipsychotics. Medications such as clozapine have been shown to have
a lower risk of TD compared to older antipsychotics, such as Haldol (haloperidol). If you develop symptoms of TD, such as grimacing,
sucking, and smacking of lips, or other movements that you cannot
control, contact your healthcare provider immediately. All
patients taking either first or second generation antipsychotics
should have an Abnormal Involuntary Movement Scale (AIMS) completed
regularly by their healthcare provider to monitor for TD.
Second
generation antipsychotics (SGAs) increase the risk of diabetes,
weight gain, high cholesterol, and high triglycerides. (See “Serious
Side Effects” section for monitoring recommendations.)
What
other medications may interact with Clozaril®/FazaClo®?
Clozapine
may lower your blood pressure. Medications used to lower blood
pressure may increase this effect and increase your risk of falling.
Propranolol (Inderal®)
is an example of this type of medication.
The
following medications may increase the risk of heart problems when
used with clozapine:
-
Antipsychotics,
such as chlorpromazine
(Thorazine®),
thioridizine (Mellaril®),
iloperidone (Fanapt®),
asenapine (Saphris®)
paliperidone (Invega®),
quetiapine (Seroquel®),
ziprasidone (Geodon®)
-
Antiarrhymics
(heart rhythm medications), such as procainamide, quinidine,
amiodarone (Cordarone®),
dronedarone (Multaq®),
sotalol (Betapace®)
The
following medications may increase the levels and effects of clozapine: ciprofloxacin (Cipro®),
fluvoxamine (Luvox®)
and lamotrigine (Lamictal®)
The
following medications may decrease the levels and effects of clozapine: carbamazepine (Tegretol®),
phenytoin (Dilantin®),
phenobarbital, and rifampin (Rifadin®)
Cigarette
smoke can decrease levels of clozapine by as much as 50%. Let your
healthcare provider know if you start or stop smoking cigarettes.
Nicotine patches do not impact clozapine levels.
How
long does it take for Clozaril®/FazaClo® to
work?
It
is very important to tell your doctor how you feel things are going
during the first few weeks after you
start taking clozapine. It will
probably take several weeks to see big enough changes in your
symptoms to decide if clozapine is the right
medication for you.
Antipsychotic
treatment is generally needed lifelong for persons with
schizophrenia. Your doctor can best discuss the duration of treatment
you need based on your symptoms and illness.
-
Hallucinations,
disorganized thinking, and delusions may improve in the first 1-2
weeks
-
Sometimes
these symptoms do not completely go away
-
Motivation
and desire to be around other people can take at least 1-2 weeks to
improve
-
Symptoms
continue to get better the longer you take clozapine
-
It
may take 2-3 months before you get the full benefit of clozapine
Provided
by
College
of Psychiatric and Neurologic Pharmacists
(January
2013)
Summary
of FDA Black Box Warnings
Agranulocytosis
Less
than 1% of patients taking clozapine may develop a condition called
agranulocytosis, Agranulocytosis causes the body to make fewer white
blood cells. A decrease in white blood cells increases the risk of
infection. If this occurs, it is reversible by stopping clozapine.
To
be safe, blood counts are checked every week for the first 6 months
and every two weeks for the next 6 months. After the first year of
treatment, blood counts are checked monthly. The pharmacy must have
a copy of your blood counts to be able to dispense the medication.
Myocarditis
Myocarditis
(inflammation of heart muscle) and cardiomyopathy (enlarged heart)
have rarely been reported. Symptoms of these heart problems include
shortness of breath and chest pain. Contact your healthcare provider
right away if this happens.
Seizures
Dose-dependent
seizures have been associated with clozapine (i.e. more likely with
high doses or rapid dose increases). Clozapine should be used with
caution in patients with a history of seizures, head injury or
alcohol dependence.
Orthostatic
hypotension
Clozapine
may cause a significant drop in blood pressure when changing position
from sitting to standing. Notify your prescriber if you feel
lightheaded when standing up.
Increased
Mortality in Elderly Patients with Dementia Related Psychosis
-
Both
first generation (typical) and second generation (atypical)
antipsychotics are associated with an increased risk of mortality in
elderly patients when used for dementia related psychosis.
-
Although
there were multiple causes of death in studies, most deaths appeared
to be due to cardiovascular causes (e.g. sudden cardiac death) or
infection (e.g. pneumonia).
-
Antipsychotics
are not indicated for the treatment of dementia-related psychosis.
