CLOPIXOL ACUPHASE INJECTION 100MG/2ML

GB-058-60-50-13410

PACKAGE LEAFLET: INFORMATION FOR THE USER

Clopixol-Acuphase zuclopenthixol acetate Read all of this leaflet carefully before you start taking this medicine 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours If any of the side effects are troubling, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist In this leaflet:
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Medicines used to lower the blood pressure such as hydralazine, alpha blockers (e.g. doxazosin) beta-blockers, methyldopa, clonidine or guanethidine Medicines that cause a disturbed water or salt balance (too little potassium or magnesium in your blood) Medicines known to increase the concentration of zuclopenthixol in your blood Medicines used to treat epilepsy Medicines used to treat diabetes Clopixol-Acuphase can reduce the effect of adrenaline (epinephrine) and similar drugs. Tell your doctor, dentist, surgeon or anaesthetist before any operation as Clopixol-Acuphase can increase the effects of general anaesthetics, muscle relaxing drugs and drugs used to prevent clots. Does Clopixol-Acuphase interact with alcohol? Clopixol-Acuphase may increase the sedative effects of alcohol making you drowsier. It is recommended not to drink alcohol during treatment with Clopixol-Acuphase. Pregnancy Ask your doctor or pharmacist for advice before taking any medicine. If you are pregnant or think you might be pregnant, tell your doctor. Clopixol-Acuphase should not be used during pregnancy unless clearly necessary. Your newborn baby might show side effects if this medicine is used during pregnancy. The following symptoms may occur in newborn babies, of mothers that have used Clopixol-Acuphase 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. Breast-feeding Ask your doctor or pharmacist for advice before taking any medicine. If you are breastfeeding, ask your doctor for advice. ClopixolAcuphase should not be used when breast-feeding, as small amounts of the medicine can pass into the breast milk. Driving and using machines There is a risk of feeling drowsy or dizzy, or suffering from blurred vision when being treated with Clopixol-Acuphase, especially at the start of your treatment. If this happens do not drive or use any tools or machines. 3. HOW CLOPIXOL-ACUPHASE IS GIVEN A small amount of Clopixol-Acuphase is drawn up into a syringe and then injected into the muscle of your buttock or thigh. Your doctor will decide on the correct amount of medicine to give. Adults The usual dose lies between 50-150 mg (1-3 ml) repeated if necessary after 2-3 days. Some patients may require an additional dose 1 or 2 days after the first injection. Treatment can continue for up to 2 weeks. In this time you may receive a total of 4 injections up to a total dose of 400 mg (8 ml). If further treatment is necessary, your doctor will prescribe suitable medication immediately or shortly after the ClopixolAcuphase injections are stopped. Elderly patients (above 65 years) Elderly patients may need smaller doses. The maximum dose per injection is 100 mg. Children Clopixol-Acuphase is not recommended for children. Patients with Liver or Kidney Disease If you have liver disease or severe kidney disease, half the usual dose will be given. If you have liver problems, the level of zuclopenthixol in your blood may be checked. If you feel that the effect of Clopixol-Acuphase is too strong or weak, talk to your doctor or pharmacist. It is important that you continue to receive your medicine at regular intervals even if you are feeling completely well, because the underlying illness may persist for a long time. If you stop your treatment too soon your symptoms may return. If you get more Clopixol-Acuphase than you should Your medicine will be given by your doctor/nurse. In the unlikely event that you receive too much Clopixol-Acuphase you may experience some symptoms. Symptoms of overdose may include: Drowsiness Unconsciousness Muscle movements or stiffness Fits Low blood pressure, weak pulse, fast heart rate, pale skin, restlessness High or low body temperature

What Clopixol-Acuphase is and what it is used for Before Clopixol-Acuphase is given How Clopixol-Acuphase is given Possible side effects How to store Clopixol-Acuphase Further information

1. WHAT CLOPIXOL-ACUPHASE IS AND WHAT IT IS USED FOR How does Clopixol-Acuphase work? Clopixol-Acuphase belongs to a group of medicines known as antipsychotics (also called neuroleptics). These medicines act on nerve pathways in specific areas of the brain and help to correct certain chemical imbalances in the brain that are causing the symptoms of your illness. What is Clopixol-Acuphase used for? Clopixol-Acuphase is used for the initial treatment of short-term psychoses including mania or increases in the severity of existing psychoses. 2. BEFORE CLOPIXOL-ACUPHASE IS GIVEN Clopixol-Acuphase is not given If you are allergic (hypersensitive) to zuclopenthixol, other thioxanthine drugs or antipsychotic drugs or any of the other ingredients of Clopixol-Acuphase (see What Clopixol-Acuphase contains). Consult your doctor if you think you might be If you are feeling less alert than usual, or are drowsy or sleepy, or have serious problems with your blood circulation Take special care with Clopixol-Acuphase If you have a heart condition, including an irregular heart beat (such as a slower heart beat); have had a recent heart attack or have problems that cause ankle swelling or shortness of breath If you have liver, kidney or thyroid problems If you suffer from epilepsy, or have been told that you are at risk of having fits (for example because of a brain injury or because of alcohol withdrawal) If you suffer from Parkinsons disease, or myasthenia gravis (a condition causing severe muscular weakness) If you have risk factors for stroke (e.g. smoking, hypertension) If you have too little potassium or magnesium in your blood or a family history of irregular heart beats If you use other antipsychotic medicines If you suffer from diabetes 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. Please talk to your doctor, even if these statements were applicable to you at any time in the past. Taking other medicines The following medicines should not be taken at the same time as Clopixol-Acuphase: Medicines that change the heartbeat (quinidine, amiodarone, sotalol, dofetilide, erythromycin, moxifloxacin, cisapride, lithium) Other antipsychotic medicines Medicines may affect the actions of other medicines and this can sometimes cause serious adverse reactions. Please tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including medicines obtained without a prescription. Tricyclic antidepressants Barbiturates or other medicines that make you feel drowsy Anticoagulant drugs used to prevent blood clots (e.g. warfarin) Anticholinergic drugs (contained in some cold, allergy or travel sickness remedies as well as other medicines) Metoclopramide (used to treat nausea and other stomach conditions) Piperazine (used to treat worm infections) Levodopa or other medicines used to treat Parkinsons disease Sibutramine (used to reduce appetite) Digoxin (to control heart rhythm) Corticosteroids (e.g. prednisolone)

INFORMATION FOR THE HEALTHCARE PROFESSIONAL CONSULT THE SUMMARY OF PRODUCT CHARACTERISTICS FOR FULL INFORMATION ON THIS PRODUCT NAME OF THE MEDICINAL PRODUCT Clopixol-Acuphase. QUALITATIVE AND QUANTITATIVE COMPOSITION Zuclopenthixol acetate 5.0% w/v equivalent to 4.526% w/v of zuclopenthixol base. PHARMACEUTICAL FORM Oily solution for deep intramuscular injection. THERAPEUTIC INDICATIONS For the initial treatment of acute psychoses including mania and exacerbation of chronic psychoses, particularly where a duration of effect of 2-3 days is desirable. DOSAGE AND METHOD OF ADMINISTRATION Adults Dosage should be adjusted according to the severity of the patient's illness. The usual dosage is 50-150 mg (1-3 ml), repeated if necessary after 2 or 3 days. Some patients may need an additional injection between 1 and 2 days after the first injection. Clopixol-Acuphase is not intended for long-term use and duration of treatment should not be more than two weeks. The maximum dosage should not exceed 400 mg and the number of injections should not exceed four. Elderly The dosage may need to be reduced in the elderly owing to reduced rates of metabolism and elimination. Maximum dosage per injection should be 100 mg. Children Not recommended for children. Reduced renal function Clopixol-Acuphase can be given in usual doses to patients with reduced renal function. Where there is renal failure dosage should be reduced to half the normal dosage. Reduced liver function Use with caution in patients with hepatic disease. Patients with compromised hepatic function should receive half the recommended dosages. Serum-level monitoring is advised. Maintenance Therapy: Clopixol-Acuphase is not intended for long-term use. A single injection of Clopixol-Acuphase has an onset of sedative action shortly after injection and an antipsychotic action persisting for 2 to 3 days. In this period, maintenance treatment with tablets or a longer acting depot neuroleptic can be initiated. The possible side-effects of long-term maintenance treatment with a neuroleptic, including tardive dyskinesia, should be considered. Maintenance treatment where required can be continued with Clopixol tablets, Clopixol injection or Clopixol conc. injection, according to the following guidelines:

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Introduce Clopixol tablets at a dosage of 20-60 mg/day in divided doses, 2 to 3 days after the last injection of Clopixol-Acuphase. If necessary, increase the tablet dosage by 10-20 mg each day up to a maximum of 150 mg/day. Or. Concomitantly with the last injection of Clopixol-Acuphase, administer 200-400 mg of Clopixol Injection or Clopixol Conc. Injection by deep intramuscular injection and repeat the Clopixol Injection or Clopixol Conc. Injection at intervals of 2 to 4 weeks. Higher dosages or a shorter interval may be necessary.

CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the excipients. Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with alcohol, barbiturates or opiates), coma. SPECIAL WARNINGS AND PRECAUTIONS FOR USE Like other neuroleptics zuclopenthixol acetate should be used with caution in patients with convulsive disorders or advanced hepatic, renal or cardiovascular disease. Zuclopenthixol is not suitable for patients who do not tolerate oral neuroleptic drugs or for patients suffering from Parkinson's disease. The possibility of development of neuroleptic malignant syndrome (hyperthermia, muscle rigidity, fluctuating consciousness, instability of the autonomous nervous system) exists with any neuroleptic. The risk is possibly greater with the more potent agents. Patients with pre-existing organic brain syndrome, mental retardation, opiate and alcohol abuse are over represented among fatal cases. Treatment: Discontinuation of the neuroleptic. Symptomatic treatment and use of general supportive measures. Dantrolene and bromocriptine may be helpful. Symptoms may persist for more than a week after oral neuroleptics are discontinued and somewhat longer when associated with the depot forms of the drug. Like other neuroleptics, zuclopenthixol should be used with caution in patients with organic brain syndrome, convulsions or advanced hepatic disease. Blood dyscrasias have been reported rarely. Blood counts should be carried out if a patient develops signs of persistent infection. An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Zuclopenthixol should be used with caution in patients with risk factors for stroke.

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Route of Administration: Deep intramuscular injection, into the upper, outer buttock or lateral thigh.

GB-058-60-50-13410

Changes in heart beat including irregular heart beat or slow heart rate You will receive treatment for any of these symptoms from your doctor or nurse. 4. POSSIBLE SIDE EFFECTS Like all medicines, Clopixol-Acuphase can cause side effects, although not everybody gets them. Serious side effects Stop using Clopixol and seek medical advice immediately if you have any of the following allergic reactions: Difficulty in breathing Swelling of the face, lips, tongue or throat which causes difficulty in swallowing or breathing Severe itching of the skin (with raised lumps) Blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any of these symptoms seek medical advice immediately. If you get any of the following symptoms you should contact your doctor immediately as your dose may need to be reduced or stopped: High fever, unusual stiffness of the muscles and changes in consciousness, especially if occurring with sweating and fast heart rate. These symptoms may be signs of a rare but serious condition called neuroleptic malignant syndrome that has been reported with the use of Clopixol and similar medicines Unusual movements of the mouth and tongue as these may be early signs of a condition known as tardive dyskinesia Unusual muscle movements (such as circular movements of the eyes), stiffness, tremor and restlessness (for example difficulty in sitting or standing still) as these may be signs of a so-called "extrapyramidal" reaction Any yellowing of the skin and the white of the eyes (jaundice); your liver may be affected Other side effects: Side effects are most pronounced the day after the first treatment and usually wear off soon afterwards. Throbbing or fast heartbeats Reduction in blood platelets (which increases the risk of bleeding or bruising) and other blood cell changes Drowsiness Loss of co-ordination or altered muscle movements (including unusual movements of the mouth, tongue and eyeballs) Tremor Stiff or floppy muscles (including stiff jaw and neck muscles) Dizziness or vertigo Headache or migraine Numbness or tingling in the arms and legs Poor concentration, loss of memory or confusion A changed walking pattern Abnormal reflexes Rigidity of the whole body Fainting Speech problems Fits Enlarged pupils or blurred, abnormal vision Sensitive hearing or ringing in the ears (tinnitus) Stuffy nose Shortness of breath Dry mouth or increase in saliva Feeling sick or vomiting Indigestion or stomach pain Flatulence (wind), constipation or diarrhoea Abnormal urination (increases or decreases in the frequency or amount) Increased sweating or greasy skin Itching, rashes or skin reactions (including sensitivity to sunlight) Skin reactions at injection site Changes in skin colour Bruising under the skin Muscle pain Raised blood levels of glucose, lipids or the hormone prolactin Loss of control of blood sugar levels Changes in appetite or weight Low blood pressure Hot flushes General weakness or pain, tiredness or feeling unwell Increased thirst Reduced or increased body temperature (including fever) Abnormal liver function tests Liver enlargement Unexpected excretion of breast milk Insomnia, abnormal dreams or nightmares Depression or anxiety Nervousness or agitation Apathy Changes to your sex drive Men may experience breast enlargement or problems with ejaculation or erections (including prolonged erections) Women may experience an absence of menstrual periods, vaginal dryness or problems with orgasms

As with other medicines that work in a way similar to zuclopenthixol (the active ingredient of Clopixol), rare cases of the following side effects have been reported: Slow heartbeat and abnormal ECG heart tracing Life threatening irregular heart beats In rare cases irregular heart beats (arrhythmias) may have resulted in sudden death. In elderly people with dementia, a small increase in the number of deaths has been reported for patients taking antipsychotics compared with those not receiving antipsychotics. If any of the side effects are troubling, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 5. HOW TO STORE CLOPIXOL-ACUPHASE Usually your doctor or nurse will store the medicine for you. If you keep it at home: Keep out of the reach and sight of children. Do not use Clopixol-Acuphase after the expiry date that is printed on the label. The expiry date refers to the last day of that month. Store Clopixol-Acuphase at or below 25C (room temperature). Keep Clopixol-Acuphase ampoules in the box, so they are protected from light. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. 6. FURTHER INFORMATION What Clopixol-Acuphase contains The active substance is zuclopenthixol acetate. Each millilitre (ml) of Clopixol-Acuphase contains 50 mg zuclopenthixol acetate. The other ingredient is thin vegetable oil (purified from coconut oil). What Clopixol-Acuphase looks like and contents of the pack Clopixol-Acuphase is an oily liquid. Clopixol-Acuphase is available in glass ampoules containing 1 ml (50 mg) or 2 ml (100 mg) in boxes of 5 ampoules. Not all pack sizes may be marketed. This injection is manufactured by: H. Lundbeck A/S Ottiliavej 9 DK-2500 Valby Denmark For any information about this medicine, please contact the Marketing Authorisation holder: Lundbeck Limited Lundbeck House Caldecotte Lake Business Park Caldecotte Milton Keynes MK7 8LG UK This leaflet was last approved in 10/2011. To request a copy of this leaflet in braille, large print or audio please call free of charge: 0800 198 5000 Please be ready to give the following information: Product name Clopixol-Acuphase Product code number PL 0458/0063

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As with other drugs belonging to the therapeutic class of antipsychotics, zuclopenthixol may cause QT prolongation. Persistently prolonged QT intervals may increase the risk of malignant arrhythmias. Therefore, zuclopenthixol should be used with caution in susceptible individuals (with hypokalaemia, hypomagnesia or genetic predisposition) and inpatients with a history of cardiovascular disorders, e.g. QT prolongation, significant bradycardia (<50 beats per minute), a recent acute myocardial infarction, uncompensated heart failure, or cardiac arrhythmia. Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Clopixol and preventive measures undertaken. Concomitant treatment with other antipsychotics should be avoided. As described for other psychotropics zuclopenthixol may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients. Increased Mortality in Elderly people with Dementia Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known. Clopixol is not licensed for the treatment of dementia-related behavioural disturbances. INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION In common with other antipsychotics, zuclopenthixol enhances the response to alcohol, the effects of barbiturates and other CNS depressants. Zuclopenthixol may potentiate the effects of general anaesthetics and anticoagulants and prolong the action of neuromuscular blocking agents. The anticholinergic effects of atropine or other drugs with anticholinergic properties may be increased. Concomitant use of drugs such as metoclopramide, piperazine or antiparkinson drugs may increase the risk of extrapyramidal effects such as tardive dyskinesia. Combined use of antipsychotics and lithium or sibutramine has been associated with an increased risk of neurotoxicity. Antipsychotics may enhance the cardiac depressant effects of quinidine; the absorption of corticosteroids and digoxin. The hypotensive effect of vasodilator antihypertensive agents such as hydralazine and -blockers (e.g. doxazosin), or methyl-dopa may be enhanced. Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co-administration of other drugs known to significantly increase the QT interval. Co-administration of such drugs should be avoided. Relevant classes include: class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide) some antipsychotics (e.g. thioridazine) some macrolides (e.g. erythromycin) some antihistamines some quinolone antibiotics (e.g. moxifloxacin)

The above list is not exhaustive and other individual drugs known to significantly increase QT interval (e.g. cisapride, lithium) should be avoided. Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalaemia) and drugs known to increase the plasma concentration of zuclopenthixol should also be used with caution as they may increase the risk of QT prolongation and malignant arrythmias. Antipsychotics may antagonise the effects of adrenaline and other sympathomimetic agents, and reverse the antihypertensive effects of guanethidine and similar adrenergic-blocking agents. Antipsychotics may also impair the effect of levodopa, adrenergic drugs and anticonvulsants. The metabolism of tricyclic antidepressants may be inhibited and the control of diabetes may be impaired. Since zuclopenthixol is partly metabolised by CYP2D6 concomitant use of drugs known to inhibit this enzyme may lead to to higher than expected plasma concentrations of zuclopenthixol, increasing the risk of adverse effects and cardiotoxicity. OVERDOSE Symptoms: somnolence, coma, extrapyramidal symptoms, convulsions, hypotension, shock, hyper or hypothermia. ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular arrhythmias have been reported when administered in overdose together with drugs known to affect the heart. Treatment: treatment is symptomatic and supportive. Measures aimed at supporting the respiratory and cardiovascular systems should be instituted. Adrenaline (epinephrine) must not be used in these patients. There is no specific antidote. LIST OF EXCIPIENTS Thin vegetable oil (derived from coconuts). INCOMPATIBILITIES Zuclopenthixol acetate should not be mixed with other injection fluids. SPECIAL PRECAUTIONS FOR STORAGE Store at or below 25C. Protect from light. SPECIAL PRECAUTIONS FOR DISPOSAL Nil. MARKETING AUTHORISATION HOLDER Lundbeck Ltd Lundbeck House Caldecotte Lake Business Park Caldecotte, Milton Keynes, MK7 8LG MARKETING AUTHORISATION NUMBER: PL 0458/0063.