CLOPIXOL-ACUPHASE

Package leaflet: Information for the user

Clopixol Acuphase, 50 mg/ml, solution for injection
Zuclopenthixol acetate
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet contents:

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

1. What Clopixol Acuphase is and what it is used for

How Clopixol Acuphase works
Clopixol Acuphase contains the active substance zuclopenthixol. Clopixol Acuphase belongs to a group of medicines called antipsychotics (also known as neuroleptics).
These medicines act on nerve pathways in certain areas of the brain and help to correct certain chemical imbalances in the brain that cause symptoms of illness.

When Clopixol Acuphase is used
Clopixol Acuphase is used in the initial treatment of acute psychoses, including mania, and acute exacerbations of chronic psychoses.

2. Important information before using Clopixol Acuphase

When not to use Clopixol Acuphase:

• if the patient is allergic (hypersensitive) to zuclopenthixil acetate or any of the other ingredients of this medicine (listed in section 6);
• if the patient has circulatory collapse, reduced consciousness (e.g. due to alcohol, barbiturates or opioids) or coma.

Warnings and precautions
Before starting treatment with Clopixol Acuphase, discuss the following with a doctor or pharmacist:

• if the patient has liver function disorders;
• if the patient has previously experienced seizures;
• if the patient has diabetes (treatment with antidiabetic medicines may need adjustment);
• if the patient has organic brain syndrome (a condition that may develop as a result of alcohol or organic solvent intoxication);
• if the patient has risk factors for stroke (e.g. smoking, hypertension);
• if the patient has hypokalaemia (low blood potassium levels) or hypomagnesaemia (low blood magnesium levels), or genetic predisposition to such abnormalities;
• if the patient has previously had cardiovascular disorders;
• if the patient is taking other antipsychotic medicines;
• if the patient or someone in their family has had venous thrombosis, as use of medicines such as this has been associated with blood clots.

Children and adolescents
Clopixol Acuphase is not recommended for this patient group.

Clopixol Acuphase with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Inform the treating doctor if the patient is taking any of the following medicines:

• tricyclic antidepressants;
• guanethidine and similar medicines (blood pressure-lowering agents);
• barbiturates and similar medicines (causing drowsiness);
• medicines used in the treatment of epilepsy;
• levodopa and similar medicines (used to treat Parkinson's disease);
• metoclopramide (a medicine used for gastrointestinal disorders);
• piperazine (an antihelminthic agent active against pinworms and roundworms);
• medicines that disturb water-electrolyte balance (low potassium or magnesium levels in blood);
• medicines known to increase blood levels of zuclopenthixil acetate, the active substance in Clopixol Acuphase.

The following medicines should not be taken concurrently with Clopixol Acuphase:

• medicines affecting heart rhythm (quinidine, amiodarone, sotalol, dofetilide, erythromycin, terfenadine, astemizole, gatifloxacin, moxifloxacin, cisapride, lithium);
• other antipsychotic medicines (e.g. thioridazine).

Clopixol Acuphase, food, drink and alcohol
Clopixol Acuphase may enhance the sedative effect of alcohol, causing drowsiness. Drinking alcoholic beverages is not recommended during treatment with Clopixol Acuphase.

Pregnancy, breastfeeding and fertility

If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
If the patient is pregnant or thinks she may be pregnant, she should inform her doctor. Clopixol Acuphase should not be used during pregnancy unless clearly necessary.

Newborns of mothers who have taken Clopixol during the third trimester (last three months of pregnancy) may experience the following symptoms: tremors, muscle stiffness and/or weakness, drowsiness, restlessness, breathing difficulties, feeding problems. If such symptoms occur in the newborn, contact a doctor immediately.

Breastfeeding
If the patient is breastfeeding, she should consult her doctor. Clopixol Acuphase should not be used by breastfeeding women, as small amounts of the medicine may be excreted in breast milk.

Fertility
Animal studies have shown that Clopixol affects fertility. The patient should consult a doctor for advice.

Driving and operating machinery
There is a risk of drowsiness and dizziness after administration of Clopixol Acuphase. If this occurs, the patient should not drive, operate machinery or use tools until these symptoms have resolved.

3. How to use Clopixol Acuphase

This medicine should always be used exactly as instructed by your doctor or pharmacist. If you are unsure,
you should consult your doctor or pharmacist.
A small volume of Clopixol Acuphase is drawn into a syringe and then injected intramuscularly into the
gluteal muscle.
Your doctor will decide the dose and frequency of injections.

Recommended dose
Adults
The usual dose of this medicine is 50 mg to 100 mg (1 to 3 ml), administered intramuscularly. If needed,
the dose may be repeated, preferably at intervals of 2 to 3 days. In some patients, an additional injection
may be required 24 or 48 hours after the first dose.

Zuclopenthixil acetate is not intended for long-term administration, and treatment must not last
longer than two weeks. The maximum cumulative dose during a single course of treatment must not
exceed 400 mg, and the number of injections must not exceed four.

For maintenance treatment, therapy should be continued with oral zuclopenthixil or intramuscular
zuclopenthixil decanoate, according to the following recommendations:

1) Switching to oral zuclopenthixil dihydrochloride
Two to three days after the last injection, a patient previously treated with 100 mg of zuclopenthixil acetate
should start taking oral zuclopenthixil dihydrochloride at a dose of approximately 40 mg per day,
preferably in divided doses. If necessary, the dose may be increased by 10–20 mg every 2 to 3 days up to
75 mg per day or higher.

2) Switching to zuclopenthixil decanoate administration
Simultaneously with (the last) injection of zuclopenthixil acetate (100 mg), the patient should receive
200–400 mg (1 to 2 ml) of zuclopenthixil decanoate intramuscularly as a solution with a concentration of 200 mg/ml.
This injection should be repeated every two weeks. Higher doses or shorter intervals between injections may be required.

Zuclopenthixil acetate and zuclopenthixil decanoate may be mixed in the same syringe and administered in a single injection.

Elderly patients (over 65 years of age)
In elderly patients, a reduced dose may be necessary. The maximum single dose should not exceed 100 mg.

Use in children
Clopixol Acuphase is not recommended for use in children.

Patients with renal impairment
Clopixol Acuphase may be administered to patients with impaired renal function at the usual recommended doses.

Patients with hepatic impairment
Patients with impaired liver function should receive half of the recommended dose. If possible, monitoring of blood drug levels is advised.

Method of administration
Clopixol Acuphase is administered by intramuscular injection into the upper outer quadrant of the buttock.
If the volume of injected medicine exceeds 2 ml, the divided dose should be administered at two separate injection sites.
Local tolerance is good.

If you feel that the effect of Clopixol Acuphase is too strong or too weak, you should consult your doctor.

Duration of treatment
This medicine is not intended for long-term therapy. Clopixol Acuphase should not be used for longer than two weeks,
and during this time, the patient should not receive more than four injections or a total of 8 ml (400 mg) of the medicine.

If further treatment is required after discontinuation of Clopixol Acuphase, your doctor will prescribe an appropriate medicine.
It is important to complete the entire course of treatment as directed by your doctor.

Overdose of Clopixol Acuphase
This medicine will be administered by a doctor or nurse, so it is unlikely that the patient will receive more than the recommended dose.

Symptoms of overdose may include:

• drowsiness;
• coma;
• abnormal movements;
• seizures;
• shock;
• elevated or reduced body temperature;
• changes in heart rate, including irregularity or bradycardia, particularly when Clopixol Acuphase has been administered in too high a dose in combination with medicines known to affect the heart.

If you have any further questions about the use of this medicine, please consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the symptoms described below occur, contact your doctor or
go to hospital immediately:

Uncommon adverse reactions (occurring in 1 in 1,000 to 1 in 100 patients):

• involuntary rhythmic movements of the lips and tongue; this may be a symptom of a condition called tardive dyskinesia.

Very rare but serious adverse reactions (occurring in less than 1 in 10,000 patients):

• high fever, excessive muscle stiffness, and disturbances of consciousness, accompanied by sweating and rapid heartbeat; these may be symptoms of a rare condition called neuroleptic malignant syndrome, which may occur after using various antipsychotic medicines.
• yellowing of the skin and whites of the eyes (jaundice), which may indicate liver damage.
• blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg skin), which may travel through blood vessels to the lungs, causing chest pain and breathing difficulties.

The adverse reactions listed below are most pronounced at the beginning of treatment, and most of them diminish as therapy continues.

Very common adverse reactions (occurring in more than 1 in 10 patients):

• drowsiness, inability to sit or stand still for a prolonged period (akathisia), involuntary movements (hyperkinesia), slowed or impaired movements (hypokinesia);
• dry mouth.

Common adverse reactions (occurring in more than 1 and less than 10 in 100 patients):

• palpitations, sensation of rapid, strong, or irregular heartbeat (palpitations);
• tremor, twisting or repetitive movements, or unusual postures due to sustained muscle contractions (dystonia), increased muscle stiffness (hypertonia), dizziness, headache, sensation of tingling skin (paresthesia), attention disturbances, forgetfulness, abnormal gait;
• disturbances in clarity of vision of objects close to the eyes (accommodation disturbances), visual abnormalities;
• sensation of spinning or swaying when the body is at rest (dizziness);
• "stuffy nose", breathing difficulties or painful breathing (dyspnea);
• increased salivation (sialorrhea), constipation, vomiting, digestive problems or discomfort in the upper abdomen (dyspepsia), diarrhea;
• disturbances in urination, urine retention, increased urine volume (polyuria);
• excessive sweating, itching (pruritus);
• muscle pain;
• increased appetite, weight gain;
• fatigue, feeling of weakness (asthenia), general discomfort or uneasiness, pain-related complaints;
• insomnia, depression, anxiety, restlessness, abnormal dreams, agitation, reduced sexual drive (decreased libido);

Uncommon adverse reactions (occurring in more than 1 in 1,000 and less than 1 in 100 patients):

• exaggerated reflexes (hyperreflexia), uncoordinated movements (dyskinesia), parkinsonism, falls (fainting), inability to coordinate muscle activity (ataxia), speech disturbances, reduced muscle tension (hypotonia), seizures, migraine;
• episode of forced upward gaze with eye rotation, dilated pupils;
• hypersensitivity to certain sound frequencies or difficulty tolerating normal (everyday) sounds, ringing in the ears;
• abdominal pain, nausea, bloating with gas release;
• rash, skin reactions due to photosensitivity (photosensitivity reactions), pigment disturbances, oily, shiny, and yellowish skin due to increased sebum secretion (seborrhea), eczema or skin inflammation, subcutaneous bleeding observed as red skin discolorations (purpura);
• muscle stiffness, inability to open the mouth normally, neck twisting, and unnatural head position (neck stiffness);
• decreased appetite, weight loss;
• low blood pressure (hypotension), hot flushes;
• thirst, abnormally low body temperature (hypothermia), fever;
• redness or pain at the injection site of Clopixol Acuphase;
• abnormal liver function test results;
• sexual disturbances (delayed ejaculation, erectile problems, in women orgasmic disturbances, vaginal dryness);
• marked indifference to the patient's surroundings (apathy), nightmares, increased sexual drive (increased libido), confusion;

Rare adverse reactions (occurring in more than 1 in 10,000 and less than 1 in 1,000 patients):

• low platelet count (thrombocytopenia), low white blood cell count (neutropenia), decreased white blood cell count (leukopenia), toxic bone marrow damage (agranulocytosis);
• elevated prolactin levels in blood (hyperprolactinemia);
• elevated blood glucose levels (hyperglycemia), impaired glucose tolerance, elevated blood lipid levels (hyperlipidemia);
• overreaction (hypersensitivity), acute systemic and severe allergic reaction (anaphylactic reaction);
• breast enlargement in men (gynecomastia), excessive milk production (galactorrhea), absence of menstruation, persistent painful erection not related to sexual stimulation (priapism);
• as observed with other medicines acting similarly to zuclopenthixol acetate (the active substance in Clopixol Acuphase), rare cases of the following adverse reactions have been reported: slow heart rate and changes in ECG recording (prolongation of QT interval);
• irregular heartbeat (ventricular arrhythmias, torsade de pointes);
• in rare cases, irregular heartbeat (arrhythmia) may lead to sudden death.

In elderly patients with dementia treated with antipsychotic medicines, a slightly higher number of deaths has been observed compared to patients not receiving antipsychotic medicines.

Reporting of adverse reactions

If any adverse symptoms occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to:
Department of Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C;
PL-02 222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Clopixol Acuphase

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Protect 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 help protect the environment.

6. Contents of the pack and other information
What Clopixol Acuphase contains

• The active substance is zuclopenthixol acetate. Each millilitre (ml) of Clopixol Acuphase contains 50 mg of zuclopenthixol acetate.
• The other ingredient is: vegetable oil (medium-chain triglycerides).

What Clopixol Acuphase looks like and contents of the pack
Clopixol Acuphase is available as a 50 mg/ml solution for injection.
Clopixol Acuphase is a clear, yellowish liquid.
Clopixol Acuphase is supplied in 1 ml (50 mg) clear glass ampoules.
The ampoules are packed in cardboard boxes containing 5 ampoules of 1 ml each.

Marketing Authorisation Holder and Manufacturer
H. Lundbeck A/S
Ottiliavej 9,
DK-2500 Valby
Denmark

For further information, please contact the representative of the Marketing Authorisation Holder.
Swixx Biopharma Sp. z o.o.
ul. Prosta 51
00-838 Warsaw, Poland
Tel. +48 22 4600 720