NeuroPsyche, Pharmacokinetics

Clozaril (clozapine) [netdoctor]

How does it work?

Clozaril tablets contain the active ingredient clozapine, which is a type of medicine known as an atypical antipsychotic.

Clozapine works in the brain, where it affects a neurotransmitter called dopamine. Neurotransmitters are chemicals that are stored in nerve cells and are involved in transmitting messages between the nerve cells.

Dopamine is a neurotransmitter known to be involved in regulating mood and behaviour, amongst other things. Schizophrenia is associated with an overactivity of dopamine in the brain, and this may be associated with the delusions and hallucinations that are a feature of this disease.

Clozapine works by blocking the receptors in the brain that dopamine acts on. This prevents the excessive activity of dopamine and helps to control psychotic illness.

Clozapine is restricted to treating schizophrenia in people who have not responded to, or are intolerant of, other treatments, as it can cause rare, but serious side effects. It is also used for treating psychotic illness in people with Parkinson’s disease where other treatments have not worked.

Clozapine is also sometimes used by specialists to treat episodes of mania in people with the psychiatric illness, bipolar affective disorder (manic depression). This is an unlicensed use of the medicine, and it is only used if other medicines have been ineffective at controlling the symptoms.

What is it used for?

  • Schizophrenia in people for whom other antipsychotic medicines are ineffective or not tolerated.

  • Psychotic disorders in people with Parkinson’s disease, in cases where standard treatment has failed to control symptoms.

  • Treatment of manic episodes resistant to standard treatment in bipolar affective disorder (unlicensed use).


  • One side effect of this medicine is that it can occasionally cause a drop in the number of white blood cells in the blood. This may be referred to as neutropenia or agranulocytosis. As this could result in potentially serious infections, you will need to have regular blood tests while you are taking Clozaril, to make sure your blood cells are not affected. These blood tests will be weekly for the first eighteen weeks of treatment, then at least every two weeks. If your blood counts are stable after a year and you are going to continue treatment, these tests can then be every four weeks for the rest of the time you take the medicine. If your white blood cell count does drop significantly, your treatment will need to be stopped and your blood cells should then recover. If you do get neutropenia or agranulocytosis you will not be able to take this medicine again.

  • You should tell your doctor immediately if you experience any signs of infection, such as flu-like symptoms, high temperature (fever), sore throat or inflammation of the lining of the mouth (stomatitis), while taking Clozaril. This type of symptom may indicate that your white blood cell count has fallen, and your blood should be tested.

  • Treatment with this medicine should only be started in people who have had their old antipsychotic dose tapered down and who have a normal blood count. People starting this medicine must be registered with the Clozaril Patient Monitoring Service.

  • Supply of this medicine is restricted to hospitals and retail pharmacies registered with the Clozaril Patient Monitoring Service. These pharmacies can only provide supplies of the medicine if the patients blood test results are normal. You will not be able to get a Clozaril prescription dispensed from pharmacies that are not registered with the Clozaril Patient Monitoring Service.

  • This medicine may rarely have an effect on the heart. For this reason you should tell your doctor if you experience any increased or abnormal heart rate, palpitations, chest pain, shortness of breath, unexplained fatigue or swelling in the legs (oedema) while taking this medicine, especially in the first two months of treatment. Your doctor may refer you to a heart specialist (cardiologist) to check your heart. In the unlikely event that your heart is affected by this medicine, your treatment should be stopped and you should not take this medicine again.

  • This medicine can sometimes cause liver problems. People with pre-existing liver disorders should have regular blood tests to monitor their liver function while taking this medicine. Consult your doctor promptly if you develop nausea, vomiting, loss of appetite, itching, yellowing of the skin or eyes (jaundice) or unusually dark urine during treatment, so that your liver function can be tested.

  • Some people may develop constipation, which may become severe, while taking this medicine. Tell your doctor if this happens, as it may need treatment.

  • This medicine can cause a drop in blood pressure when moving from lying down or sitting to a sitting or standing posisiton, and this may make you feel dizzy or cause you to faint. This is more likely to occur when starting treatment and if you are taking certain other medicines (see below). People with Parkinson’s disease who have been prescribed this medicine should have their blood pressure regularly monitored during the first weeks of treatment.

  • This medicine can cause some people to put on weight. Talk to your doctor about this before you start treatment so that you can discuss strategies, such as diet and exercise, for minimising any weight gain.

  • This medicine may cause drowsiness. If affected do not drive or operate machinery. Alcohol should be avoided.

  • Consult your doctor immediately if you experience the following symptoms while taking this medicine: high fever, sweating, muscle stiffness, faster breathing and drowsiness or sleepiness. These symptoms may be due to a rare side effect known as the neuroleptic malignant syndrome, and your treatment may need to be stopped.

  • The components of tobacco smoke can cause clozapine to be removed from the body faster than normal. This means that if you are a smoker and then give up while you are taking clozapine, your blood level of clozapine may increase. Tell your doctor if you plan to give up smoking while you are taking clozapine.

  • Drinking caffeine can cause your blood level of clozapine to increase. If you regularly drink caffeine and then suddenly stop for a few days, this may cause your blood level of clozapine to fall below normal. For this reason you should try not to make big changes to your normal caffeine intake while you are taking this medicine.

  • It is recommended that if treatment with this medicine is stopped, this should be done gradually over one to two weeks. You should not suddenly stop taking this medicine unless your doctor tells you to (for example because of problems with your white blood cells). After stopping treatment your blood will still need to be monitored for at least a further four weeks.

Not to be used in

  • Children under 16 years of age.

  • People unable to have regular blood tests.

  • People with low levels of white blood cells in their blood.

  • People with a history of a drop in white blood cell count (agranulocytosis/granulocytopenia) caused by clozapine or other medicines (except cancer chemotherapy), or with no known cause.

  • People taking other medicines that can decrease white blood cell count (see below for examples).

  • People with bone marrow disorders.

  • Uncontrolled epilepsy.

  • Active liver disease associated with nausea, loss of appetite or jaundice.

  • Worsening liver disease or liver failure.

  • Severe kidney disorders.

  • People with paralysis or inactivity in the intestines that is stopping material passing through the gut (paralytic ileus).

  • Severe heart disorders, eg inflammation of the muscular walls of the heart (myocarditis).

  • People who have previously experienced heart problems (myocarditis or cardiomyopathy) while taking clozapine.

  • Failure of the blood circulatory system (circulatory collapse).

  • Unresponsive unconscious states (comatose states).

  • People with reduced awareness, slow reactions or drowsiness due to medicines, drugs or illness that reduce activity in the central nervous system.

  • Drug intoxication.

  • Psychosis due to drugs or alcohol.

  • Breastfeeding.

  • Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Clozaril tablets contain lactose).

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Use with caution in

  • Elderly people.

  • People with a history of bone marrow disorders.

  • People with a history of heart disease.

  • People with a personal or family history of an abnormal heart rhythm seen on a heart monitoring trace (ECG) as a ‘prolonged QT interval’.

  • Elderly people with dementia (antipsychotic medicines have been shown to increase the risk of stroke in this group of patients).

  • People with risk factors for having a stroke, for example a history of stroke or mini-stroke (TIA), smoking, diabetes, high blood pressure, or a type of irregular heartbeat called atrial fibrillation.

  • Liver disorders.

  • Kidney disorders.

  • History of epilepsy.

  • Closed angle glaucoma.

  • Diabetes.

  • Enlarged prostate gland (prostatic hypertrophy).

  • Constipation.

  • People taking medicines that can cause constipation.

  • People a history of disorders involving the large bowel (colon).

  • People who have had lower abdominal surgery.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • The safety of this medicine for use during pregnancy has not been established. It should only be used during pregnancy if the benefits of treatment to the mother outweigh any risks to the developing baby. It is recommended that women who could get pregnant use effective contraception to avoid getting pregnant while taking this medicine. (NB. Women who had no periods or irregular periods while taking a previous antipsychotic medicine may find their periods return when they are changed to clozapine.) Seek further advice from your doctor.

  • This medicine may pass into breast milk and could be harmful to a nursing infant. Mothers who need to take this medicine must not breastfeed and should bottlefeed instead. Discuss this with your doctor.

Label warnings

  • Follow the printed instructions you have been given with this medication.

  • This medication may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Very common (affect more than 1 in 10 people)

  • Drowsiness or sedation.

  • Dizziness.

  • Increased heart rate (tachycardia).

  • Constipation – see warning section above.

  • Increased salivation.

Common (affect between 1 in 10 and 1 in 100 people)

  • Decrease in the number of a type of white blood cell (neutrophil) in the blood (neutropenia) – see warning section above.

  • Weight gain – see warning section above.

  • Blurred vision.

  • Headache.

  • Abnormal movements of the hands, legs, face, neck and tongue, eg tremor, twitching, rigidity (extrapyramidal effects).

  • Anxiety, restlessness and agitation (akathisia).

  • Seizures.

  • Increased blood pressure (hypertension).

  • A drop in blood pressure that occurs when going from lying down to sitting or standing, which may result in dizziness, lightheadedness or fainting (postural hypotension) – see warning section above.

  • Nausea and vomiting.

  • Loss of appetite.

  • Dry mouth.

  • Difficulty passing urine or urinary incontinence.

  • Fatigue.

  • Fever.

  • Interference with the body’s temperature regulation (this is more common in elderly people and may cause heat stroke in very hot weather or hypothermia in very cold weather).

Uncommon (affect between 1 in 100 and 1 in 1000 people)

  • Sudden severe deficiency in the number of white blood cells in the blood (agranulocytosis) – see warning section above.

  • High temperature combined with falling levels of consciousness, paleness, sweating and a fast heart beat (neuroleptic malignant syndrome). Requires stopping the medicine and immediate medical treatment. See warning section above.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

  • Anaemia.

  • Diabetes.

  • Confusion.

  • Delirium.

  • Difficulty or pain when swallowing (dysphagia).

  • Abnormal heartbeats (arrhythmias).

  • Inflammation of the muscular walls of the heart (myocarditis) or other heart problems – see warning section above.

  • Blood clots in the blood vessels (thrombosis) that may detach and travel in the circulation to another area of the body (thromboembolism).

  • Liver disorders – see warning section above.

Very rare (affect less than 1 in 10,000 people)

  • Increase or decrease in the number of blood cells called platelets in the blood.

  • Very high blood glucose level (hyperglycaemia).

  • Raised levels of fats such as cholesterol or triglycerides in the blood.

  • Slow, shallow breathing (respiratory depression).

  • Rhythmical involuntary movement of the tongue, face, mouth and jaw, which may sometimes be accompanied by involuntary movements of the arms and legs.

  • Obstruction of the intestines or faecal impaction.

  • Prolonged erection (priapism).

  • Kidney problems.

The side effects listed above may not include all of the side effects reported by the medicine’s manufacturer.For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

Tell your doctor if you are taking any medicines, including those bought without a prescription and herbal medicines, before you start treatment with clozapine. Similarly, check with your doctor or pharmacist before you take any new medicines while you are taking clozapine, so that they can make sure the combination is safe.

The risk of a drop in white blood cells is greater if clozapine is taken with other medicines that can have this effect, such as the following. These medicines should not be taken in combination with clozapine:

  • antipsychotics given as a depot injection

  • azapropazone

  • carbamazepine

  • chemotherapy medicines for cancer

  • chloramphenicol

  • co-trimoxazole

  • penicillamine

  • phenylbutazone

  • sulphonamides, eg sulfadiazine.

If clozapine is taken with lithium or other antipsychotic medicines there may be an increased risk of developing side effects. Other antipsychotics should not generally be used in combination with clozapine.

There may be an increased risk of drowsiness and sedation if clozapine is taken with any of the following, which can also cause drowsiness:

  • alcohol

  • barbiturates, eg amobarbital, phenobarbital

  • benzodiazepines, eg diazepam, temazepam

  • MAOI antidepressants, eg phenelzine

  • sedating antihistamines, eg chlorphenamine, hydroxyzine

  • sleeping tablets, eg zopiclone

  • strong opioid painkillers, eg morphine, codeine

  • tricyclic antidepressants, eg amitriptyline.

There may be an increase in side effects such as dry mouth, constipation, confusion or heat stroke (in hot and humid conditions) if clozapine is taken with other medicines that have anticholinergic effects, including the following:

  • anticholinergic medicines for Parkinson’s symptoms, eg procyclidine

  • antihistamines, eg brompheniramine, chlorphenamine

  • other antipsychotic medicines

  • antisickness medicines, eg promethazine, meclozine, cyclizine

  • antispasmodic medicines, eg hyoscine

  • medicines for urinary incontinence, eg oxybutynin, flavoxate, tolterodine, propiverine, trospium

  • MAOI antidepressants, eg phenelzine

  • muscle relaxants, eg baclofen

  • tricyclic antidepressants, eg amitriptyline.

Clozapine may enhance the blood pressure-lowering effects of medicines that lower blood pressure, including medicines used to treat high blood pressure (antihypertensives) and medicines that lower blood pressure as a side effect, eg benzodiazepines. If you are taking medicines that lower blood pressure you should tell your doctor if you feel dizzy or faint after starting treatment with this medicine, as your doses may need adjusting.

Clozapine may oppose the effect of levodopa and medicines for Parkinson’s disease that work by stimulating dopamine receptors in the brain, for example ropinirole, pergolide, bromocriptine.

Clozapine may oppose the effect of anticonvulsant medicines used to treat epilepsy.

Clozapine may increase the blood levels of the following medicines:

  • digoxin

  • warfarin.

There may be an increased risk of an abnormal heart rhythm (seen as a ‘prolonged QT interval’ on a heart monitoring trace or ECG) if clozapine is taken with any of the following medicines:

  • antiarrhythmics (medicines to treat abnormal heart beats), eg amiodarone, procainamide, disopyramide, sotalol

  • the antihistamines astemizole, mizolastine or terfenadine

  • atomoxetine

  • certain antidepressants, eg amitriptyline, imipramine, maprotiline

  • certain antimalarials, eg halofantrine, chloroquine, quinine, mefloquine, Riamet

  • certain other antipsychotics, eg thioridazine, chlorpromazine, sertindole, haloperidol

  • cisapride

  • intravenous erythromycin or pentamidine

  • moxifloxacin

  • medicines that can alter the levels of salts such as potassium or magnesium in your blood, eg diuretics such as furosemide.

The following medicines may increase the breakdown of clozapine in the body and so could make it less effective:

  • omeprazole

  • phenytoin

  • rifampicin.

The following medicines may prevent the breakdown of clozapine in the body and so could increase the chance of its side effects:

  • cimetidine

  • ciprofloxacin

  • erythromycin

  • protease inhibitors for HIV infection, eg ritonavir, fosamprenavir

  • SSRI antidepressants, eg citalopram, fluoxetine, fluvoxamine, paroxetine or sertraline

  • venlafaxine.

Other medicines containing the same active ingredient

Denzapine Zaponex

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