Israel - English - Ministry of Health
PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE
PHARMACISTS’ REGULATIONS (PREPARATIONS) – 1986
The medicine is dispensed with a doctor’s prescription only
Instructions for issuing this preparation:
During the first 18 weeks:
Perform a blood test once a week during the first 18 weeks.
The local pharmacy will dispense the medicine for one week of
treatment only, according to a doctor’s prescription, provided that it
carries a stamp as follows:
“White blood cell test has been conducted and results are normal”.
Starting from week 19 of treatment:
A blood test must be conducted at least once a month.
The local pharmacy will dispense the medicine for one month of
treatment only, according to a doctor’s prescription, provided that it
carries a stamp as follows:
“White blood cell test has been conducted and results are normal”.
Lozapine 25 mg Tablets
Lozapine 100 mg Tablets
Active ingredient and quantity:
Active ingredient and quantity:
Each tablet contains:
Each tablet contains:
Clozapine 25 mg
Clozapine 100 mg
For a list of inactive ingredients, please refer to section 6.
Read this leaflet carefully in its entirety before using the medicine.
This leaflet contains concise information about the medicine. If you have
further questions, refer to the doctor or pharmacist.
This medicine has been prescribed for the treatment of your ailment. Do
not pass it on to others. It may harm them, even if it seems to you that
their ailment is similar.
This medicine is not intended for infants and children below the age of 16,
as there is not enough information on its use in this age group.
Prior to starting treatment with Lozapine, you must perform a blood test to
ensure that you may take the medicine.
Since the medicine may cause a decrease in the number of white
blood cells, a white blood cell count and a differential blood count
must be performed prior to beginning treatment. The treatment may
be started only if the blood count is found to be normal.
A white blood cell count should be performed every week for the
first 18 weeks of treatment, and then, at least every 4 weeks, as
long as the patient is taking Lozapine.
If an infection is found and/or the blood count is below 3500/mm
is significantly lower than the baseline (even if the count is above
leukocytes and granulocytes must be checked twice a week.
If the white blood cell count is below 3000/mm
and an absolute
count of neutrophil granulocytes is below 1500/mm
, stop treatment
with Lozapine immediately and continue conducting white blood cell
counts for 4 weeks after stopping the medicine.
granulocytes are less than 1000/mm
, consult a hematologist about
If treatment was stopped due to the decrease in white blood cell
count below 3000/mm
and absolute count of neutrophils below
, do not resume patient's treatment with Lozapine.
WHAT IS THIS MEDICINE INTENDED FOR?
For the treatment of schizophrenia when there is no response to
other medicines or when other medicines are causing intolerable side
BEFORE USING THE MEDICINE:
.X. Do not use the medicine:
If you are sensitive (allergic) to the active ingredient (clozapine) or to
any of the other ingredients of the medicine listed in section 6
If you are breastfeeding.
If you are unable to have regular blood tests.
If you have previously been told that you have a low white blood cell
count (for instance: leukopenia or agranulocytosis), especially if this
was caused by medicinal treatment (excluding chemotherapy).
If you suffer or have ever suffered from bone marrow disease, or if
you take medicines that suppress bone marrow activity.
If you take medicines that reduce the number of white cells in your
If you had to stop taking Lozapine previously because of severe side
effects (e.g., agranulocytosis or heart problems).
If you suffer from uncontrolled epilepsy (seizures or fits).
If you have a severe mental illness caused by alcohol or medicines
If you suffer from an inflammation of the heart muscle (myocarditis)
or if you suffer from some other severe heart disease.
If you suffer from any severe kidney disease.
If you have symptoms of an active liver disease such as jaundice
(yellowing of the skin and eyes, nausea, and loss of appetite), or if
you suffer from any other severe liver disease or from liver failure.
If you suffer from reduced consciousness and severe drowsiness.
If you suffer from circulatory collapse which may occur as a result of
severe shock and/or central nervous system suppression for any
If you suffer or have previously suffered from severe constipation,
paralytic ileus (your bowel does not work properly and you have
severe constipation) or any other condition affecting the bowel.
If you are being or have been treated in the past with long-acting
injections of antipsychotics.
In persons who are unconscious or in a coma.
In any of the aforementioned situations, inform your doctor and do
not take Lozapine.
Special warnings regarding the use of the medicine:
Lozapine may cause dizziness or fainting, especially in the beginning
of treatment due to a decrease in your blood pressure.
If you experience dizziness or fainting caused by Lozapine, be careful
when standing up from a lying or sitting position.
If you must have surgery, or if for any reason, you are unable to walk
for long time, you must tell your doctor that you are taking Lozapine.
You may be at risk of thrombosis (a blood clot in the veins).
experiencing the following side effects during treatment: fainting or
dizziness after changing position, dizziness, rapid heartbeat, difficulty
urinating, and constipation.
If you are older (age 60 and up), tell the doctor if you have dementia
or psychotic states resulting from dementia.
If you experience any of the following symptoms, inform your doctor
Consult your doctor immediately upon appearance of the first
sign of cold, flu, fever, sore throat, white spots on the lips, ulcers in
the oral cavity or any other infection. Lozapine may reduce the
number of white blood cells and lead to high susceptibility to
infection. Your doctor may examine your blood count and take
additional measures if required.
Consult your doctor immediately if you experience rapid and
irregular heart beat that persist at rest, possibly accompanied by
shortness of breath and swelling of the feet or legs. These effects
may occur, in particular in the beginning of treatment, and your
doctor may be required to take additional measures.
Potentially fatal heart attacks have been reported for Lozapine.
Lozapine may cause drowsiness and prolonged stay in bed,
accompanied by weight gain, which may result in blood clots in
.!. Before beginning treatment with Lozapine, tell the doctor if:
you suffer, or have suffered in the past from blood clots or have a
family history of blood clots, as medicines from this type have been
associated with formation of blood clots in the past.
you suffer, or have suffered in the past from glaucoma (increased
you suffer, or have suffered in the past from diabetes. High levels of
sugar in the blood (sometimes, considerably high) have occurred in
patients with or without medical history of diabetes (see section 4
you suffer, or have suffered in the past from problems with your
prostate gland, or difficulty urinating.
you suffer, or have suffered in the past from any heart, and/or blood
vessel, kidney/urinary system or liver disease.
you suffer, or have suffered in the past from chronic constipation, or if
you suffer, or have suffered in the past from galactose intolerance,
Lapp-lactase deficiency, or glucose-galactose malabsorption.
you suffer, or have suffered in the past from controlled epilepsy.
you suffer, or have suffered in the past from colon diseases.
you have undergone abdominal surgery in the past.
you have had heart disease in the past or have a family history of
abnormal conduction in the heart called 'prolongation of the QT
You have had a stroke or are at risk of stroke, for instance, if you
have high blood pressure, cardiovascular problems, or problems with
the blood vessels in the brain.
you are sensitive to any food or medicine.
including non-prescription medicines and nutritional supplements,
tell the doctor or pharmacist.
Do not take Lozapine with medicines that suppress bone marrow activity
and/or reduce the number of blood cells generated by the body, for
carbamazepine to treat epilepsy.
certain painkillers: pyrazolone analgesics such as phenylbutazone.
penicillamine, a medicine used to treat rheumatoid arthritis.
cytotoxic agents - chemotherapeutic medicines.
long-acting injections of antipsychotic medicines.
These medicines increase the risk of developing agranulocytosis (lack of
white blood cells).
Taking Lozapine may affect how other medicines work or they might affect
how Lozapine works. Tell your doctor or pharmacist if you are taking:
medicines used to treat depression such as: lithium, fluvoxamine,
fluoxetine, and sertraline.
other antipsychotic medicines used to treat mental illnesses.
benzodiazepines and other medicines used to treat anxiety and sleep
narcotics and other medicines which can affect your breathing.
medicines for epilepsy such as phenytoin and valproic acid.
adrenaline and noradrenaline.
warfarin, a medicine used to prevent blood clots.
antihistamines, medicines used for colds or allergies such as hay
cramps, spasms and travel sickness.
medicines used to treat Parkinson’s disease.
digoxin, a medicine used to treat heart problems.
medicines used to treat a fast or irregular heartbeat.
Certain medicines used to treat stomach ulcers, such as omeprazole
some antibiotics, such as erythromycin and rifampicin.
ketoconazole) or viral infections (such as protease inhibitors, used to
atropine, a medicine which may be used in some eye drops or cough
and cold preparations.
adrenaline, a medicine used in emergency situations.
.!. Use of the medicine and food:
caffeine (coffee, tea, cola). A sudden change in caffeine drinking habits
can change the effect of Lozapine.
.!. Use of the medicine and alcohol consumption:
Do not drink wine or alcoholic beverages during the course of treatment
with the medicine.
Lozapine may enhance the effects of alcohol.
.!. Pregnancy and breastfeeding:
If you are pregnant or breastfeeding, consult the doctor or pharmacist
before using medicines.
Before using Lozapine, tell the doctor if you are pregnant or you think that
you might be pregnant. The doctor will discuss with you the benefits and
possible risks of using the medicine during pregnancy. Tell your doctor
immediately if you become pregnant during treatment with the medicine.
The following symptoms may occur in newborn babies of mothers who
have used Lozapine in the last trimester of pregnancy: tremor, muscle
stiffness and/or weakness, sleepiness, restlessness, agitation, breathing
problems and difficulty in feeding. In some cases, these symptoms resolve
Intensive Care Unit or hospitalization.
If your baby develops these symptoms, contact a doctor.
Do not breastfeed during the course of treatment with the medicine.
Clozapine, the active ingredient of Lozapine, may pass into breast milk
and affect your baby.
Women of childbearing age, contraceptive methods:
Some women taking certain antipsychotic medications have irregular
periods or no periods at all. Your periods might return when the treatment
with other antipsychotic medicine is changed to Lozapine. In these
circumstances, you must use an effective contraceptive.
.!. Driving and using machinery:
Using this medicine might cause drowsiness, especially at the beginning
of treatment. Therefore, refrain from driving or operating machines until
you get used to the medicine and the drowsiness disappears. In any case,
take care while driving a car, operating machines and performing any
activity requiring alertness.
Tell the doctor if you smoke. A sudden change in smoking habits can
change the effect of Lozapine.
Elderly (60 years of age and above):
may adjust the treatment for you if you are 60 years old or
Children and adolescents:
Treatment of children below the age of 16 is not recommended due to lack
The preparation contains lactose. If you have been told by a doctor that
you have intolerance to some sugars, inform the doctor before using this
HOW SHOULD YOU USE THE MEDICINE?
Always use according to the doctor’s instructions. Check with the
doctor or pharmacist if you are uncertain.
To minimize the risk of low blood pressure, seizures, and sleepiness,
the doctor will increase your dosage gradually.
It is important that you do not change your dosage or stop taking the
medicine without consulting the doctor. Continue taking the tablets
according to the doctor's instructions.
If you are 60 years of age or older, your doctor may start you on a
lower dosage and increase it more gradually because you are at
higher risk of developing undesirable side effects (see section 2
“Special warnings regarding use of the medicine”).
The dosage and manner of treatment will be determined by the
doctor only. The usual dosage is generally:
The usual starting dosage is 12.5 mg (one half of a 25 mg tablet) once or
twice on the first day, followed by 25 mg once or twice on the second day.
If tolerated well, your doctor will then gradually increase the dosage in
intervals of 25-50 mg over the next 2-3 weeks until a dose of 300 mg per
day is reached. After that, if necessary, the daily dosage may be increased
in intervals of 50-100 mg at half-weekly intervals, or preferably, at weekly
The effective dosage is usually between 200 mg and 450 mg, divided into
several doses a day. Some people might need a higher dosage. A daily
dosage of up to 900 mg is allowed. Increased side effects (particularly
seizures) are possible at daily dosages over 450 mg. Always take the
lowest effective dosage for you.
Most people take part of their dosage in the morning and part in the
evening. The doctor will instruct you exactly how to divide your daily dose.
If your daily dosage is only 200 mg, you can take this as a single dose in
Taking Lozapine at the same time every day will help you remember when
you have to take the medicine.
Once you have been taking Lozapine with successful results for some
time, the doctor may try to lower the dosage. You will need to take
Lozapine for at least 6 months.
Do not exceed the recommended dose.
Do not chew. Swallow the medicine with water.
Tests and follow-up
Before beginning use of the medicine, the doctor will check your medical
history and refer you to blood tests to ensure that your white blood cell
count is normal. This is very important because your body needs white
blood cells to fight infections. You can start treatment only if the blood
count is normal.
Be sure to have regular blood tests before you start treatment, during
treatment and after you stop treatment with the medicine (for at least 4
weeks). The doctor will give you instructions about this. It is important to
perform all the blood tests as recommended by the doctor.
The medicine may cause a severe decline in white blood cell count
(agranulocytosis) - Regular blood tests are the only way for the doctor to
know if you are at risk of developing agranulocytosis.
The doctor will also perform a physical examination prior to beginning
treatment. The doctor may also perform an ECG to check your heart, but
only if this test is essential, or if you have specific concerns.
If you have liver problems, you should regularly perform liver function tests
for as long as you are taking the medicine.
If you have high levels of blood sugar (diabetes), the doctor may regularly
test your blood sugar levels.
Lozapine may cause alterations in blood lipids. Lozapine may cause
weight gain. The doctor will monitor your weight and blood lipid levels.
If you accidentally took a higher dosage
or if a child has accidentally
swallowed the medicine, refer immediately to a doctor or proceed to a
hospital emergency room, and bring the package of the medicine with you.
unconsciousness, coma, confusion, hallucinations, agitation, incoherent
speech, stiff limbs, trembling hands, seizures (fits), increased production of
saliva, dilation of the black part of the eye, blurred vision, low blood
If you forgot to take this medicine
at the scheduled time, take a dose as
soon as you remember. If the next scheduled dose is close (there are less
than 4 hours before the next dose), skip the forgotten dose and take the
next dose at the scheduled time. Never take a double dose to compensate
for a forgotten dose. If you have not taken Lozapine for more than 48
hours, do not resume treatment with the medicine and contact the
as soon as possible.
Be sure to adhere to the treatment regimen as recommended by the
Even if there is an improvement in your health, do not stop treatment with
the medicine without consulting the doctor.
If you stop taking the medicine
Do not stop taking the medicine without consulting the doctor because you
excessive sweating, headache, nausea, vomiting, and diarrhea.
experience any of these signs, refer to the doctor immediately. If you
do not receive immediate treatment, these signs may be followed by
more serious side effects.
Your original symptoms may return. If you need to stop treatment, the
will gradually reduce the dosage for one to two weeks. The doctor
will advise you how to decrease your daily dosage.
If you need to stop treatment immediately, you will have to be checked by
If the doctor decides that you must restart Lozapine treatment and the last
dose was taken more than two days earlier, start at a dosage of 12.5 mg.
Do not take medicines in the dark! Check the label and the dose each
time you take the medicine. Wear glasses if you need them.
If you have further questions regarding use of the medicine, consult the
doctor or pharmacist.
As with any medicine, use of Lozapine may cause side effects in some
users. Do not be alarmed by the list of side effects. You may not suffer
from any of them.
Refer to the attending doctor immediately before taking the next
With the first signs of cold, fever, flu-like symptoms, throat-ache, or
other signs of infection. You will have to have blood tests urgently to
check whether these symptoms are related to the medicine.
If you experience a sudden and quick rise in body temperature,
muscle rigidity which can lead to loss of consciousness (neuroleptic
malignant syndrome), because you may be suffering from a serious
side effect that requires immediate treatment.
If you experience severe chest pain, pressure or crushing pain in the
chest (chest pain may radiate to left arm, jaw, neck, and upper
Proceed to an emergency room immediately.
If you have rapid and irregular heartbeat, even at rest, palpitations,
breathing problems, chest pain, or unexplained tiredness. The doctor
will examine your heart and, if necessary, will refer you immediately
to a cardiologist.
If you experience a sensation of pressure, heaviness, crushing pain,
burning or constriction in the chest (signs of inadequate blood and
oxygen flow to the heart muscle). The doctor will examine your heart.
If you are nauseous, if you vomit and/or lose your appetite. The
doctor will examine your liver.
If you have severe constipation. The doctor will treat it to prevent
If you have signs of respiratory tract infection or pneumonia, such as
fever, cough, difficulty breathing, wheezing.
If you have signs of blood clots in the veins, especially in the legs
(symptoms include swelling, pain, and redness in the leg), which may
travel through the blood vessels to the lungs and cause chest pain
and difficulty breathing.
If you experience excessive sweating, headache, nausea, vomiting
and diarrhea (symptoms of cholinergic syndrome).
If you experience a severe decline in quantity of urine (signs of kidney
If you experience seizures.
If you are a man and you suffer from a painful and prolonged
erection. This effect is called priapism. If you experience an erection
lasting for more than 4 hours, you may require immediate medical
treatment to avoid complications.
Additional side effects:
Drowsiness, dizziness, fast heartbeat, constipation, increased production
of saliva, low levels of white blood cells (leukopenia), high level of white
blood cells (leukocytosis), high levels of a specific type of white blood cell
inability to initiate movement, inability to remain motionless, high blood
temperature, speech disorders (e.g. slurred speech), changes in ECG.
syndrome (a disorder characterized by high fever, impaired consciousness
and muscle stiffness), speech disorders (e.g., stuttering), blood pressure
fluctuations, lack of orientation.
Low levels of red blood cells (anemia), restlessness, agitation, confusion,
hallucinations, circulatory collapse, irregular heartbeat, inflammation of the
heart muscle (myocarditis) or of the membrane surrounding the heart
muscle (pericarditis), fluid build up around the heart (pericardial effusion),
difficulty in swallowing (for instance, food going down the wrong way),
respiratory tract infection and pneumonia, high levels of sugar in the blood:
excessive thirst, dry mouth and excessive urination may be signs of high
levels of sugar in the blood (diabetes mellitus) – if you experience any of
them, inform the doctor as soon as possible since Lozapine may cause or
exacerbate diabetes, blood clots in the lungs (thromboembolism),
inflammation of the liver (hepatitis), liver disease causing yellowing of the
skin and eyes/dark urine/itching/nausea and/or loss of appetite,
inflammation of the pancreas leading to severe upper abdominal pain,
raised levels of enzymes in the blood called creatinine phosphokinase,
significant drop in blood pressure.
Occurring very rarely:
Increase in the number of blood platelets, with possible clotting in the
blood vessels, decrease in the number of blood platelets (which may be
manifested by bleeding or spontaneous bruising), uncontrollable
movements of mouth/tongue and limbs, involuntary purposeless
movements such as twitching, lip smacking, rapid eye blinking, obsessive
(enlargement of the saliva glands), difficulty breathing, complications due
to uncontrolled blood sugar levels (such as coma or ketoacidosis), very
high levels of triglycerides or cholesterol in the blood, disorder of the heart
obstruction of the bowel (paralytic ileus), swollen abdomen, abdominal
pain, severe liver damage (fulminant hepatic necrosis, appearing suddenly
and developing very fast), inflammation of the kidneys, persistent painful
erection (priapism), sudden unexplained death.
Occurring at unknown frequency:
Blood clots in the veins, excessive sweating, headache, nausea, vomiting
and diarrhea (symptoms of cholinergic syndrome), strong chest pain,
shortness of breath (symptoms of heart attack), pressure or heaviness in
the chest (signs of insufficient oxygen and blood flow to the heart muscle),
severely decreased urine output (sign of kidney failure), hepatic disorders
including fatty liver disease, death of liver cells, liver injury / toxicity,
hepatic disorders including replacement of normal liver tissue by scar
tissue, which leads to loss of liver function, including those life threatening
cases such as liver failure (which may lead to death), liver injury (injury of
liver cells, bile duct in the liver or both) and liver transplantation, allergic
reaction (swelling mainly of the face, mouth, throat and tongue, which may
cause pain or itching), rash, red- purple spots, fever or itching due to
inflammation of blood vessels, colitis leading to diarrhea, abdominal pain,
fever, skin discoloration; butterfly rash on the face, joint pain, muscle pain,
fever and tiredness (lupus erythematosus); a sudden and uncontrollable
permanent and involuntary muscle contraction, and involuntary muscle
contractions which may lead to twisted movements of the body or body
parts (pleurothotonus); in men – an ejaculation disorder associated with
entry of semen into the urinary bladder instead of being discharged via the
penis (a dry orgasm or retrograde ejaculation), changes in brain waves (in
electroencephalogram/EEG test), diarrhea, stomach discomfort after a
meal, heartburn, muscle weakness, muscle spasms, muscle pain, runny
nose, bedwetting at night.
In elderly people with dementia, a small increase in the number of people
dying has been reported for patients taking antipsychotics compared with
those not taking antipsychotics.
If you suffer from any side effect, consult the doctor or the pharmacist.
This also includes side effects not mentioned in the leaflet.
Reporting side effects:
You can report side effects to the Ministry of Health (MoH) by following the
link ‘Reporting Side Effects of Medication’ on the MoH home page
(www.health.gov.il) which links to an online form for reporting side effects,
or by clicking the link:
HOW SHOULD THE MEDICINE BE STORED?
Avoid poisoning! This medicine, and any other medicine, should be
kept in a safe place out of the reach and sight of children and/or
infants in order to avoid poisoning. Do not induce vomiting unless
explicitly instructed to do so by the doctor!
Do not use the medicine after the expiry date (exp. date) appearing
on the package. The expiry date refers to the last day of that month.
Store in a cool and dry place, below 25°C.
Close tightly and prevent penetration of air and moisture.
Do not discard medicines in the wastewater or in the waste bin. Ask
your pharmacist how to dispose of medicines that are no longer in
use. These measures will help to protect the environment.
In addition to the active ingredient, the medicine also contains:
Lactose monohydrate, pregelatinized starch, povidone, maize starch, talc,
colloidal anhydrous silica, magnesium stearate.
Each Lozapine 25 mg tablet contains: 48 mg lactose.
Each Lozapine 100 mg tablet contains: 192 mg lactose.
What does the medicine look like and what are the contents of the
Lozapine 25 mg: round, yellow, odorless tablets, with a dividing line on
both sides and “CPN 25” engraved on one side.
Lozapine 100 mg: round, yellow, odorless tablets, with a dividing line on
both sides and “CPN 100” engraved on one side.
Each carton package contains blisters with 50 tablets.
License holder and address:
Taro International Ltd., 14 Hakitor St.,
Haifa Bay 2624761.
Manufacturer and address:
Genthon BV, Nijmegen, the Netherlands.
Registration number of the medicine in the National Drug Registry of
the Ministry of Health:
Lozapine 25 mg tablets: 116 44 29643
Lozapine 100 mg tablets: 116 45 29644
This leaflet was checked and approved by the Ministry of Health in April