CLOPINE®

Clozapine 25, 50, 100 and 200 mg tablets

What is in this leaflet

This leaflet provides some useful information on CLOPINE tablets.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

What CLOPINE tablets are used for

CLOPINE tablets belong to the group of medicines known as
antipsychotics. This group of medicines is mainly used in the treatment of
schizophrenia. Schizophrenia is a mental illness with disturbances in
thinking, feelings and behaviour.

This medicine is only used in patients with schizophrenia for whom other
antipsychotic medicines have not worked or have caused severe side effects.

This medicine is thought to work by correcting the chemical imbalances in
the brain, which may cause mental illness.

Your doctor may have prescribed it for another reason.

Ask your doctor if you have any questions about why this medicine has
been prescribed for you.

This medicine is available only with a doctor's prescription.

Before you take CLOPINE tablets

When you must not take it

Do not take this medicine if you have an allergy or have ever
experienced an allergic reaction to the active ingredient, clozapine, or to
any of the other ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to this medicine may include:

• breathing problems such as shortness of breath, wheezing, difficulty
  breathing
• skin rash, itching or hives
• swelling of the face, lips, tongue or other parts of the body

Do not take this medicine if you have a low white blood cell count, or
if you have previously had a low white blood cell count caused by use of a
medicine.

CLOPINE tablets can cause agranulocytosis. With this condition, the
number of white blood cells (which are needed to fight infections) is reduced.
If you have a low white blood cell count or have had one in the past, you must
not take this medicine.

Do not take CLOPINE tablets if you have or have had any of the following
medical conditions:

• paralytic ileus, a small bowel condition
• bone marrow disorder
• Problems with your kidneys
• reduced function of the circulatory or nervous system
• symptoms of active liver disease such as jaundice (yellowing of the skin
  and eyes, feeling sick, loss of appetite) or liver failure
• uncontrolled epilepsy (fits or seizures)
• acute mental illness caused by alcohol or another drug.
• Inflammation of heart muscle (myocarditis)
• Any severe heart disorder

CLOPINE tablets must not be given to anyone who is unconscious or in a
coma.

Clopine must not be given to children under 16 years.

Do not take this medicine if the expiry date (EXP) shown on the outer
container, on the blister strip or on the bottle has passed. Do not use if the
tablets show signs of deterioration or if the packaging shows signs of
tampering.

If you take this medicine after the expiry date has passed, it may not
work as well or you may feel unwell.

If you are not sure whether you should start taking this medicine, talk to
your doctor or pharmacist.

Before you start to take it

Tell your doctor if you have any allergies to:

• any other medicines
• any other substances such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or are thinking of becoming
pregnant during treatment with CLOPINE tablets.

There is limited information on the safety of clozapine in
pregnancy. Your doctor will discuss the risks and benefits of taking this
medicine during pregnancy.

Make sure you use a contraceptive to prevent pregnancy during treatment
with CLOPINE.

Tell your doctor if you are breast-feeding or plan to breast-feed.

It is recommended that you do not breast-feed while taking CLOPINE
tablets, as clozapine may pass into breast milk and therefore there is a
possibility that the breast-fed baby may be affected.

Tell your doctor if you have or have had any medical conditions,
especially the following:

• heart disease or a family history of heart disease
• diseases of liver or kidneys or family history of liver and kidney
  problems
• orthostatic hypotension - feeling dizzy or faint when standing
  especially in the elderly
• anticholinergic effects -confusion and excitement especially in the
  elderly
• prostate problems especially in the elderly
• fits or epilepsy that is under control
• diabetes
• glaucoma (raised pressure in the eye)
• bone marrow disorder
• neuroleptic malignant syndrome (NMS) - a reaction to some medicines with
  a sudden increase in body temperature, sweating, fast heart beat, muscle
  stiffness and fluctuating blood pressure, which may lead to coma
• a condition called tardive dyskinesia characterised by uncontrollable
  twitching or jerking of the arms or legs
• chronic constipation.

Your doctor may want to take special precautions if you have any of these
conditions.

Tell your doctor if you smoke and how much coffee you drink. Nicotine
and coffee can affect the amount of clozapine in your body. Sudden changes in
your usual smoking or coffee drinking habits can also change the effects of
this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines,
including any that you buy without a prescription from your pharmacy,
supermarket or health food shop.

Some medicines and CLOPINE tablets may interfere with each other.
These include:

• medicines which may decrease the number of blood cells produced by your
  body
• drugs which depress bone marrow function eg. cotrimoxazole,
  chloramphenicol, sulphonamides, penicillamine, carbamazepine and
  antineoplastics should not be used concurrently.
• strong pain killers eg. morphine
• antihistamines - medicines used to control and prevent symptoms of
  allergies such as hay fever
• anticholinergic medicines used to relieve stomach cramps, spasms and
  travel sickness
• Parkinson's disease medicines
• high blood pressure medicines
• medicines used to treat a fast or irregular heart beat eg. digoxin
• atropine - a medicine which may be used in some eye drops or cough
  preparations
• adrenaline - a drug used in emergency situations
• warfarin or heparin - medicines used to prevent blood clots
• medicines used for stomach ulcers eg. cimetidine, omeprazole
• medicines used to treat bacterial infections eg. erythromycin,
  rifampicin
• epilepsy medicines eg phenytoin, carbamazepine, valproic acid
• other medicines for schizophrenia, mental disorders, depression or mood
  swings
• medicines to treat heart conditions
• sleep inducing medicines
• nicotine in medicines used to help you quit smoking eg. nicotine patches
  or chewing gum.
• medicines used to treat fungal and viral infections.
• St John's wort (Hypericum perforatum) - a herbal remedy.

These medicines may be affected by CLOPINE tablets or may
affect how well CLOPINE tablets work. Your doctor will advise you.

Your doctor and pharmacist may have more information on medicines to be
careful with or avoid while taking this medicine.

Be careful driving or operating machinery until you know how this
medicine affects you.

You may feel tired, drowsy, dizzy or you may feel faint while taking this
medicine, especially during the early stages of treatment. If you have any of
these symptoms, do not drive, operate machinery or do any tasks where you need
to be alert.

There is no evidence that this medicine is addictive.

How to take CLOPINE tablets

Your dose of CLOPINE tablets has been determined for you by your
doctor. The dose will depend on how you respond to the medicine, other
medicines you are taking, and other medical conditions that you may have. The
dose may be altered from time to time.

Carefully follow all directions given to you by your doctor.

Their directions may differ from the information contained in this
leaflet.

If you do not understand the instructions on the label, ask your doctor
or pharmacist for help.

How much to take

Your doctor will determine the most appropriate dose for you.

Take CLOPINE tablets exactly as prescribed by your doctor.

If you have heart, kidney or liver disease, epilepsy or you are elderly;
your doctor may start you on a lower dose and gradually increase the dose to
prevent unwanted effects.

Do not take more or less CLOPINE tablets than your doctor has
prescribed.

If you think the dose is too weak or too strong, talk to your doctor.

How to take it

The total daily amount of CLOPINE tablets is usually divided into
two doses. However, if your total dose is 200mg or less, your doctor may allow
you to take the whole amount in one dose, usually in the evening.

Swallow CLOPINE tablets with a full glass of water or other liquid.

When to take it

Take your medicine at about the same time each day.

Taking your tablets at the same time each day will have the best effect.
It will also help you to remember when to take the tablets.

It does not matter if you take this medicine before or after food.

If you forget to take it

If it is almost time for your next dose (within four hours), skip the
dose you missed and take your next dose when you are meant to. Otherwise take
it as soon as you remember, and then go back to taking your tablets as you
would normally.

If you miss a dose of CLOPINE tablets, do not take a double dose to make
up for the missed dose. If you have stopped taking CLOPINE tablets for more
than two days, do not start taking it again before you contact your doctor.

To prevent unwanted side effects, your doctor will probably restart you on
CLOPINE tablets at a lower dose and increase it gradually back
to your normal dose.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your
pharmacist for some hints.

How long to take it

Take this medicine until your doctor tells you to stop.

Your doctor will check your progress and decide how long to continue your
treatment. This medicine helps to control your condition, but does not cure
it. It is important to keep taking your medicine even if you feel well.

Do not lower the dosage, even if you are feeling better, unless your
doctor tells you to do so.

Your condition may worsen if you suddenly stop taking it. Your doctor will
gradually reduce the amount you take each day before stopping the medicine
completely.

Do not let yourself run out of tablets over the weekend or on holidays.

If you have any concerns, talk to your doctor.

Do not give the tablets to anyone else even if their symptoms seem
similar or they have the same condition as you.

While you are taking CLOPINE tablets

Things you must do

You must have strict and regular blood tests while taking this medicine.

This medicine can cause agranulocytosis. This is a condition where the
number of white blood cells (which are necessary to fight infection in your
body) may be reduced. There is no way of knowing who is at risk of developing
agranulocytosis.

Severe cases of agranulocytosis have resulted in deaths. However, with
regular blood tests, agranulocytosis can be detected early, and if this
medicine is stopped as soon as possible, the white blood cell numbers
should return to normal.

After starting on this medicine, you must have a blood test at least
once a week for the first 18 weeks of treatment (this is when the risk of
agranulocytosis is greatest), thereafter at least every 4 weeks for as long as
you are taking this medicine, and for one month after stopping.

Your doctor will advise if blood tests are required more often. These tests
will tell the doctor if the white blood cell count is dropping.

There are some situations where you may need to have blood tests more often
(eg. twice a week). Your doctor will talk to you about this

If the number of your white blood cells falls below a safe level, this
medicine must be stopped immediately and you must never take any medicines
containing clozapine again.

Tell any other doctors, dentists, and pharmacists who are treating you
that you are taking CLOPINE or if you are about to be started on any new
medicines or if you plan to have surgery.

Do not take this medicine to treat any other complaints unless your
doctor tells you to.

If you become pregnant while taking this medicine, tell your doctor
immediately.

Be sure to keep all of your doctor's appointments so that your progress
can be checked.

Things to be careful of

Be careful driving or operating machinery until you know how this
medicine affects you.

If the tablets make you feel dizzy, light-headed or faint, be careful
when getting up from a sitting or lying position.

This medicine may lower your blood pressure, especially at the start of
treatment. Getting up slowly and flexing leg muscles and toes to get the blood
circulating can usually prevent these symptoms. When getting out of bed,
dangle your legs over the side for a minute or two before standing up.

Be careful when drinking alcohol or when taking antihistamines
(medicines used for hay fever, allergies or colds), sleeping tablets or
tablets to relieve pain while taking this medicine.

Clozapine can increase drowsiness caused by alcohol and by medicines
affecting your nervous system.

Clozapine may affect the way your body controls temperature, and it may
prevent sweating even in very hot weather. Exercise, hot baths or saunas may
make you feel dizzy or faint while you are taking this medicine.

Side effects

All medicines have side effects. Some of these are serious most of them are
not. You may need medical treatment if you get some of the side effects. Your
doctor changing the dose can relieve some of the side effects of this
medicine.

If you are over 65 years old, you may have an increased chance of getting
side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist as soon as possible if you notice any of
the following:

• Feeling anxious
• vivid dreams
• blurred vision.
• constipation
• dizziness, fainting, light-headedness
• dry mouth
• headache
• increased or decreased sweating
• mild fever
• nausea, vomiting
• prolonged erection
• tiredness and drowsiness
• excessive saliva;
• weight gain

These are the more common side effects of this medicine.

If any of the following happen, tell your doctor immediately or go to
your nearest Accident & Emergency department or clinic:

• develop a fast or irregular heart beat that is present even when you are
  resting, accompanied by rapid breathing, shortness of breath, dizziness or
  light headedness, or chest pain,
  
  These symptoms could be signs of myocarditis, an inflammation of the
  heart muscle, or another heart condition.
• sore throat, mouth ulcers, fever, any "flu-like" symptoms such as
  swollen glands or other signs of infection as these symptoms may be an early
  sign of agranulocytosis. Flu-like symptoms may also be a sign of
  myocarditis.
• signs of an allergic reaction such as itching, skin rash, hives,
  swelling of the face, lips or tongue, difficulty in swallowing or breathing
• signs that blood clots may have formed, such as sudden severe headache,
  sudden loss of coordination, blurred vision, slurred speech, numbness in an
  arm or leg
• confusion/disorientation
• loss of co-ordination
• seizures or fits
• jaundice, yellowing of the skin and/or eyes
• urinary problems - difficulty passing urine (water) or blood in the
  urine; loss of bladder control
• signs of loss of blood sugar control such as excessive thirst, passing
  large amounts of urine, dry mouth and skin
• persistent painful erection
• severe headache
• blurred vision or loss of vision
• muscle spasms, stiffness
• abdominal or lower back pain
• stomach pain accompanied by nausea and vomiting
• slurred speech
• unusual bruising or bleeding

These are serious side effects. You may need urgent medical
treatment.

If any of the following happen, STOP taking this medicine and tell your
doctor immediately or go to your nearest Accident & Emergency department or
clinic:

• if you have muscle weakness, fever, fast or irregular heart beat and
  excessive sweating. These are symptoms of a very rare condition called
  Neuroleptic Malignant Syndrome (NMS) - a reaction to some medicines,
  which can cause a sudden increase in body temperature.
• if you have uncontrolled movements of the tongue, jaw (such as puffing
  at the cheeks, chewing movements, puckering of the mouth), face and mouth.
  These are symptoms of a very rare condition called tardive

  dyskinesia - a condition more likely to happen during long term
  treatment, especially in older women

These conditions may develop in people who are taking other medicines in
addition to CLOPINE tablets, or may be due to medicines you were taking
before starting CLOPINE tablets. These symptoms may not be
reversible.

These are very serious side effects. You may need urgent
medical attention or hospitalisation.

Other side effects not listed above may occur in some patients. Tell
your doctor or pharmacist if you notice anything else that is making you
unwell. Do not be alarmed by this list of possible side effects.

You may not experience any of them.

Overdose

Immediately contact a doctor or Poisons Information Centre (telephone
0800 POISON or 0800 764 766), or go to the your nearest Accident and Emergency
department or clinic, if you think that you or someone else may have taken too
much of this medicine. Do this even if there are no signs of discomfort or
poisoning.

The most common signs and symptoms of clozapine overdose include:
drowsiness, confusion and coma; light-headedness; shallow breathing or
breathing more slowly; fast or irregular heartbeat and dribbling.
Occasionally, fits have also been reported.

Storage conditions

Keep your tablets in the original container until it is time to take
them. If you leave the tablets out of the original container they will not
keep well.

Keep your tablets in a cool dry place away from light where the
temperature stays below 30°C.

Do not store your tablets or any other medicine in the bathroom or near
a sink. Do not leave it in the car or on a windowsill.

Heat and dampness can destroy medicines.

As with all medicines, you should store your tablets out of the
reach of children.

A locked cupboard at least one-and-a-half metres above the ground is a good
place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the tablets
have passed their expiry date, ask your pharmacist what to do with any that
are left over.

Product Description

What it looks like

CLOPINE 25 - 25 mg tablets are small, round, yellow tablets
with "25" embossed over a breakline on one face, the other side is plain.

CLOPINE 50 - 50 mg tablets are small, round, yellow tablets with
"50" embossed over a breakline on one face, the other side is plain.

CLOPINE 100 - 100 mg tablets are small, round, yellow tablets with
"100", embossed over a breakline on one face, the other side is plain.

CLOPINE 200 - 200 mg tablets are oval shaped yellow tablets with
"200" embossed on one side and a breakline on the other side.

Pack Sizes:

CLOPINE 25, CLOPINE 50, CLOPINE 100 and CLOPINE 200
tablets come in packs of 50 or 100 tablets.

Your doctor will determine the quantity provided to you by the pharmacy.

Ingredients

Active ingredient: clozapine

Other ingredients: povidone, microcrystalline cellulose, lactose, sodium
starch glycollate, magnesium stearate.

This medicine does not contain sucrose, gluten, tartrazine or any other azo
dyes.