• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes possible side effects not listed in this leaflet. See section 4.

1. What Denzapine is and what it is used for
2. What you need to know before you take Denzapine
3. How to take Denzapine
4. Possible side effects
5. How to store Denzapine
6. Contents of the pack and other information

• if you are allergic to clozapine or to any of the other ingredients of this medicine (listed in section 6). It is important to tell your doctor if you think you have ever had an allergic reaction to any of these ingredients. Symptoms of an allergic reaction can include:
  • swelling of the face and mouth
  • itchy skin rashes or hives
  • difficulty breathing
  • faintness.
• if you are unable to digest lactose (milk sugar), due to one of the following conditions:
  • galactose intolerance
  • total lactase deficiency
  • glucose-galactose malabsorption.
• if you are unable to undergo regular blood tests
• if you have a low number of white cells in the blood (leucopenia/granulocytopenia/agranulocytosis) especially if this was caused by medicines. This does not apply if you have had low white blood cell count caused by previous chemotherapy.
• if you are receiving treatment with other medicines that can cause a fall in the number of white blood cells
• if you are being treated or have been treated with long-acting depot injections of antipsychotics
• if you have suffered from a very low white blood cell count (agranulocytosis) caused by previous treatment with clozapine.

Do not take Denzapine if you have any of the following diseases:

• Disorders of the bone marrow (when the bone marrow does not make enough blood cells) or have ever suffered from bone marrow disease
• Uncontrolled epilepsy (fits or seizures)
• Acute mental illness caused by alcohol, medicines or other substances (e.g. narcotics)
• Poisoning caused by other medicines
• Circulatory collapse (a very pronounced fall in the blood pressure that may lead to unconsciousness)
• Disorders affecting the brain that can lead to severe drowsiness, reduced consciousness or unconsciousness
• Severe kidney disease
• Heart disease (such as myocarditis (inflammation of heart muscle), pericarditis or cardiomyopathy (weakness of heart muscle))
• Active liver disease with jaundice (yellow colouration of the skin and eyes), feeling sick and loss of appetite
• Liver failure (very serious liver disease) or any other severe liver disease
• Paralytic ileus (a disorder of the small intestine)
• If you use any medicine that stops your bone marrow from working properly.

The safety measures mentioned in this section are very important. You must comply with them to minimise the risk of serious life-threatening side effects.

Talk to your doctor or pharmacist before taking Denzapine if you have or have had any medical conditions or illnesses, especially the following:

• Low number of white blood cells (leucopenia, neutropenia, granulocytopenia, agranulocytosis)
• High number of a certain type of white blood cells called eosinophil granulocytes (eosinophilia)
• Low number of platelets in the blood (thrombocytopenia)
• Pericarditis or pericardial effusion (inflammation of the membranes around the heart)
• If you have had a heart disease or family history of abnormal conduction in the heart called “prolongation of the QT interval”
• Orthostatic hypotension (a fall in the blood pressure on standing up)
• Epilepsy or fits, even if they are well controlled
• Any heart, kidney, or liver disease
• Enlargement of the prostate or difficulty urinating
• Glaucoma (raised pressure in the eye)
• Severe or chronic constipation or if you are taking medicines which cause constipation (such as anticholinergics)
• Paralytic ileus, disease of the large bowel or operations on the abdomen
• Diabetes. Increased blood sugar levels have occurred in patients with or without diabetes mellitus in their medical history (see section 4).
• Stroke (risk factors of stroke e.g. smoking, diabetes and high blood pressure)
• If you or someone else in your family has a history of blood clots, as medicines like these have been associated with formation of blood clots. If you are not mobile you are at increased risk of developing blood clots while taking Denzapine.

Talk to your doctor or pharmacist immediately

• if you experience an elevated temperature (fever). This may be caused by Neuroleptic Malignant Syndrome - a serious reaction to some anti-psychotic medicines. Symptoms include a sudden increase in body temperature, sweating, a fast heart beat, muscle stiffness and a fluctuating blood pressure. It can lead to coma. Stop taking Denzapine immediately if your doctor or pharmacist tells you.
• if you get signs of a cold, fever, flu-like symptoms, sore throat or any other infection. You will have to have an urgent blood test to check if your symptoms are related to your medicine.
• if you have fast and irregular heart beat, even when you are at rest, palpitations, breathing problems, chest pain or unexplained tiredness. Your doctor will need to check your heart and if necessary refer you to a cardiologist immediately.
• if you experience nausea (feeling sick), vomiting (being sick) and/or loss of appetite. Your doctor will need to check your liver.
• if you have severe constipation, abdominal pain, abdominal tenderness, fever, bloating and/or bloody diarrhoea. Your doctor will have to treat this in order to avoid further complications.

Tell your doctor if you are taking any other antipsychotic medicines (see section “Taking other medicines” below).

Tell your doctor if you are taking any other medicines that are known to affect the heart.

Denzapine may lower the number of your white blood cells, making you more prone to infections. Before and during your treatment with Denzapine, your doctor will monitor your blood count closely to make sure that the number of your white blood cells do not fall under a certain level. Tell your doctor immediately if you develop any signs of infection, such as fever, sore throat or flu-like symptoms.

Your doctor will tell you exactly when and where to have the tests. Denzapine may only be taken if you have a normal blood count.

Denzapine can cause agranulocytosis. In this condition, the number of white blood cells (which are necessary to fight infection) is too low. If this occurs, you are at risk of suffering infections which may be life-threatening. Warning signs include flu-like symptoms, a sore throat or fever. If you develop these or any other signs suggestive of infection, you must contact your doctor immediately.

There is no way of knowing who is at risk of developing agranulocytosis. Deaths have occurred in severe cases of agranulocytosis, although with regular blood tests, agranulocytosis can be detected early. If Denzapine is stopped as soon as a problem is detected, the white blood cell numbers should return to normal. You must understand the importance of regular blood tests by your doctor while taking Denzapine.

After starting treatment with Denzapine, you will have a blood test once a week for the first 18 weeks. The risk of agranulocytosis is highest in this period. For the rest of the first year of treatment, blood tests will be performed every 2 weeks. After the first year, tests will be performed every 4 weeks for as long as you continue to take Denzapine. Tests will also be performed for one month after stopping the medicine. These tests will tell the doctor if there is any problem with the number of white cells in your blood. There are some situations where you may need to have blood tests more often (e.g. twice a week). Your doctor will talk to you about this.

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

You will need to have blood tests for another 4 weeks after the end of Denzapine treatment.

Your doctor will also do a physical examination before starting treatment. Your doctor may do an electrocardiogram (ECG) to check your heart, but only if this is necessary for you, or if you have any special concerns.

Denzapine may cause alteration in blood lipids (fats), and may cause weight gain. Your doctor may monitor your weight and blood lipid level.

If you have a liver disorder you will need regular liver function tests for as long as you continue to take Denzapine.

If Denzapine makes you feel light-headed, dizzy or faint, or if you already suffer from these feelings, be careful when getting up from a sitting or lying position as this may increase the possibility of falling.

If you have to undergo surgery or if for some reason you are unable to walk around for a long time, discuss with your doctor the fact that you are taking Denzapine. You may be at risk of thrombosis (blood clotting within a vein).

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.

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

Denzapine 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.

Do not use Denzapine if you are under 16 years of age because there is not enough information about its use in this age group.

Some side effects are more common in older people: feeling dizzy or faint when you stand up or change position, fast heart beat, difficulty passing urine, and constipation.

Tell your doctor or pharmacist if you suffer from Dementia.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Do not take Denzapine together with medicines that stop the bone marrow from working properly and/or decrease the number of blood cells produced by the body, such as:

• Medicines that affect the bone marrow. These can decrease the number of blood cells produced by the bone marrow. They include:
  • some antibiotics (e.g. co-trimoxazole, chloramphenicol, sulphonamides)
  • certain pain-killers (e.g. phenylbutazone, oxybutazone, antipyrine, dipyrone)
  • penicillamine (for rheumatoid arthritis)
  • carbamazepine (for epilepsy and for neuralgic pain)
  • cytotoxic (anticancer) medicines
  • other antipsychotic medicines (neuroleptics), especially when given as a depot (for long-term treatment).

Taking Denzapine at the same time as another medicine may affect how well Denzapine and/or the other medicine works. Tell your doctor if you plan to take, if you are taking (even if the course of treatment is about to end) or if you have recently had to stop taking any of the following medicines:

• Medicines that can make you drowsy e.g. morphine (for pain), benzodiazepines (for anxiety or as sleeping pills) and antihistamines (for allergies or colds) such as loratadine, chlorpheniramine
• Other antipsychotic medicines used to treat mental illnesses such as perazine
• Anticholinergic medicines, which are used to relieve stomach cramps, spasms and travel sickness
• Medicines used to treat high blood pressure, e.g. metoprolol, captopril, enalapril
• Medicines used to treat a fast or irregular heart beat (antiarrhythmics, e.g. flecainide, pilsicainide)
• Medicines that can cause changes on the heart trace (ECG). Your doctor will know which medicines these are.
• Medicines that can cause constipation, particularly certain medicines to treat psychosis, depression or Parkinson’s disease. Your doctor will know which medicines these are.
• Atropine, a medicine which may be used in some eye drops or cough preparations
• Medicines which may cause excessive salt loss, such as diuretics (water tablets)
• Adrenaline (epinephrine), a medicine used in emergency situations
• Warfarin, a medicine to prevent blood clots
• Digoxin (for heart diseases)
• Cimetidine, used for stomach ulcers
• Erythromycin and rifampicin (antibiotics)
• Medicines to treat fungal infections, such as ketoconazole, itraconazole and miconazole
• Medicines to treat epilepsy e.g. phenytoin, carbamazepine, valproic acid
• Medicines for depression, such as fluvoxamine, fluoxetine, paroxetine, sertraline, citalopram, amitriptyline, phenelzine, moclobemide, chlorpromazine, mesoridazine or fluphenazine
• Lithium (for mental disorders)
• Medicines which affect how your body eliminates clozapine. Your doctor will know which medicines these are.
• Omeprazole (a drug used to treat excess stomach acid)
• Ciprofloxacin (a drug used to treat infections)
• Hormonal contraceptives (birth control tablets)
• Medicines used to treat viral infections such as protease inhibitors used to treat HIV infection.

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

You can take your Denzapine tablets with or without food.

Do not drink alcohol during treatment with Denzapine.

Caffeine can affect the levels of clozapine (the active substance of Denzapine) in your blood.

You may drink coffee, tea, cola and other drinks containing caffeine. However, if you stop drinking caffeine suddenly, the levels of clozapine in your blood may fall. This will make the medicine less effective. Equally, if you start drinking caffeine, the levels may rise, increasing the risk of side effects.

Smoking can affect the levels of clozapine in your blood. If you stop smoking suddenly, the levels of clozapine in your blood may rise. This may increase the risk of side effects.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. There is limited information on the safety of Denzapine tablets in pregnancy. Your doctor will discuss with you the risks and benefits of taking this medicine during pregnancy.

The following symptoms may occur in newborn babies, of mothers that have used Denzapine in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms you may need to contact your doctor.

Do not breast-feed when using Denzapine because the active ingredient, clozapine, can reach your baby through your breast milk.

Some women taking antipsychotic medicines have irregular or no periods. If you have been affected in this way, your periods may return when your medication is changed to Denzapine.

In these circumstances you should be sure to take adequate contraceptive precautions.

You may feel tired, drowsy, dizzy or you may feel faint while taking Denzapine, 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.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

The total amount of Denzapine you take each day is usually divided into two doses. If you have to divide your dose, you should take the larger dose at bed time. However, if your total daily dose is not over 200 mg, it is not necessary to divide the dose. In this case, it is usually taken in the evening.

Swallow Denzapine tablets with a full glass of water or other liquid. Taking the tablets at the same time each day will have the best effect and will help you remember to take them.

When you first start taking Denzapine, the usual dose is half a 25 mg tablet (12.5 mg) taken once or twice on the first day, followed by one or two 25 mg tablets taken on the second day. If this dose is well tolerated, it may be increased gradually, usually to between 200 mg and 450 mg per day.

However, some people may need a higher dose. The maximum permissible dose is 900 mg per day. Once the maximum benefit is achieved, your doctor may reduce the dose gradually to a lower level. Your doctor will determine the most appropriate dose for you.

The initial dose is of 12.5 mg (half a 25 mg tablet) taken in the evening. The dose is gradually increased to a maximum of 50 mg per day, taken in the evening. Increases in the dosage should be stopped or postponed if you feel faint, light-headed or confused. In order to avoid such symptoms your blood pressure will be monitored during the first weeks’ treatment.

The effective dose is usually between 25 mg and 37.5 mg (one to one-and-a-half 25 mg tablets). If the 50 mg dose is not effective, it can be increased to 100 mg in some patients. This dose (100 mg) must not be exceeded. Always take the lowest effective dose for you.

If you have a liver disorder you will need regular liver function tests for as long as you continue to take Denzapine.

Denzapine is not recommended for use in children and adolescents.

Denzapine tablets can be used in the elderly (over 65 years of age). Treatment usually begins with a lower dose (e.g. 12.5 mg daily), which is then gradually increased.

You should take Denzapine for at least 6 months. Do not stop taking this medicine without first talking to your doctor.

Tell all of the doctors and pharmacists who are treating you that you are taking Denzapine. You must have regular blood tests while taking Denzapine.

Before starting Denzapine you will have a blood test to make sure that you can take this medicine.

If you suspect that you or someone else has taken too many Denzapine tablets, contact a doctor immediately or go to the Accident and Emergency Department at your nearest hospital. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Keep the telephone numbers for these places handy.

The most common signs and symptoms of overdose include:

• drowsiness
• confusion and coma
• delirium
• agitation
• lack of energy
• light-headedness
• hallucinations
• a fall in the blood pressure
• collapse
• widening of the black part of the eye, blurred vision
• shallow or slow breathing or sometimes shortness of breath
• fast or irregular heart beat
• dribbling
• fits.

If it is almost time for your next dose (within four hours), leave out the dose you missed and take your next dose at its normal time. 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 Denzapine do not take a double dose to make up for the missed dose.

If you have stopped taking Denzapine for more than two days, you must contact your doctor before starting to take it again. In this case, the medicine must be started again at a low dose and then increased.

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

Do not stop taking Denzapine or lower the dosage even if you are feeling better, unless your doctor tells you to do so because you might get withdrawal reactions. These reactions include sweating, headache, nausea (feeling sick), vomiting (being sick) and diarrhoea. If you have any of the above signs, tell your doctor straight away. These signs may be followed by more serious side effects unless you are treated immediately. 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.

If the medicine needs to be stopped abruptly due to side effects, you will be monitored closely for psychotic symptoms. Other symptoms can also arise, including increased sweating, headache, nausea (feeling sick), vomiting and diarrhoea.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

United Kingdom

Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is clozapine.

One Denzapine 25 mg tablet contains 25 mg clozapine.

One Denzapine 50 mg tablet contains 50 mg clozapine.

One Denzapine 100 mg tablet contains 100 mg clozapine.

One Denzapine 200 mg tablet contains 200 mg clozapine.

• The other ingredients are:
  Microcrystalline cellulose
  Lactose monohydrate
  Povidone
  Sodium starch glycolate
  Magnesium stearate.

Denzapine 25 mg tablets are small, round, yellow tablets with “25”embossed over a breakline on one face, the other side is plain.

Denzapine 50 mg tablets are small, round, yellow tablets with “50”embossed over a breakline on one face, the other side is plain.

Denzapine 100 mg tablets are small, round, yellow tablets with “100” embossed over a breakline on one face, the other side is plain.

Denzapine 200 mg tablets are large, oval shaped, yellow tablets with “200” on one side and a breakline on the other side.

The breakline allows the tablet to be broken for easier swallowing.

Denzapine 25 and 100 mg tablets are supplied in bottles of 100 tablets and in blister packs containing 28 or 84 tablets.

Denzapine 50 mg tablets are supplied in bottles of 50 or 100 tablets and in blister packs containing 20, 50 or 100 tablets.

Denzapine 200 mg tablets are supplied in bottles of 50 or 100 tablets and in blister packs containing 20 or 50 tablets.

Not all pack sizes may be marketed.

The quantity provided to you by the pharmacy will be determined by your doctor.

If you have any further questions about your medicine or are unsure about any of the advice in this leaflet, ask your doctor or pharmacist.

Denzapine 25 mg tablets PL 04483/0067

Denzapine 50 mg tablets PL 04483/0068

Denzapine 100 mg tablets PL 04483/0069

Denzapine 200 mg tablets PL 04483/0070