Sereprile

Patient Information Leaflet

Sereprile 100 mg tablets, 100 mg/2 ml injectable solution

tiapride
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sereprile is and what it is used for

Sereprile contains Tiapride, which belongs to a class of medicines called "antipsychotics".
Sereprile is indicated for the treatment of a hereditary (genetic) disease called Huntington's disease,
which causes disturbances in muscle coordination and leads to memory and learning impairments
(cognitive decline) as well as psychiatric problems.
This medicine is used to treat certain behavioural disorders caused by alcohol consumption.
This medicine is used to treat certain behavioural disorders in elderly patients.

2. What you need to know before taking Sereprile

Do not take Sereprile:

• if you are allergic to tiapride or to any of the other ingredients of this medicine (listed in section 6);
• if you have a condition called "prolactin-dependent tumour" (e.g. prolactinoma of the pituitary gland);
• if you have breast cancer;
• if you have a tumour (confirmed or suspected) of the gland located above the kidneys (pheochromocytoma);
• if you are taking levodopa or other medicines used to treat Parkinson's disease (see "Other medicines and Sereprile").

Warnings and precautions
Talk to your doctor or pharmacist before taking Sereprile.
Inform your doctor immediately:

• if you develop fever and/or muscle rigidity during treatment with Sereprile, especially if you are already taking any other medicine for mental health conditions.

• if you have or have had problems with alcohol (see "Sereprile and alcohol").

Take particular care before taking Sereprile:

• if you have Parkinson's disease. In this case, Sereprile should be used only in exceptional cases;
• if you suffer from epilepsy. During treatment with Sereprile, you may experience more frequent seizures; your doctor will need to monitor you closely;
• if you have impaired kidney function (renal insufficiency), your doctor will reduce your dose because use of Sereprile could lead to loss of consciousness (coma) due to overdose (see "How to take Sereprile" and "If you take more Sereprile than you should");
• if you have serious heart or blood circulation disorders (cardiovascular and haemodynamic conditions), particularly if you suffer from low blood pressure (hypotension);
• if you are elderly, because use of Sereprile may cause low blood pressure (hypotension), decreased level of consciousness, and coma.

During treatment with Sereprile, a disease causing a severe decrease in white blood cells (severe neutropenia) may occur. In such a case, your doctor will discontinue Sereprile until your white blood cell count returns to normal.
With medicines of the same class as Sereprile (antipsychotics), decreases in certain types of blood cells (leucopenia, neutropenia, and agranulocytosis) have been reported. Unexplained infections or fever may indicate a blood disorder (haematological dyscrasia - see "Possible side effects"), requiring immediate blood tests.
If you are receiving Sereprile injections, especially intravenous injections, you may experience reduced blood volume (hypovolemia) or sudden drops in blood pressure when standing up or exerting yourself (orthostatic hypotension).
Tiapride may cause a heart condition called "QT interval prolongation", which increases the risk of serious heart rhythm disorders (such as ventricular arrhythmia, including torsade de pointes; see "Possible side effects"). Before taking Sereprile, your doctor will check your heart condition to assess whether risk factors for heart rhythm disturbances are present, such as:

• if you have a condition causing slow heart rate (bradycardia, less than 55 beats per minute);
• if you have an imbalance of certain substances in the blood (electrolytes), particularly low potassium levels (hypokalaemia);
• if you have congenital heart rhythm abnormalities (congenital QT interval prolongation);
• if you are taking other medicines that cause:
• slow heart rate (bradycardia);
• imbalance of certain substances in the blood (electrolytes);
• heart function disturbances (decreased intracardiac conduction or QT interval prolongation; see "Other medicines and Sereprile").

Your doctor will monitor your heart condition, especially if you have other heart or blood circulation disorders (cardiovascular conditions) or if family members have "QT interval prolongation".
As with other medicines acting on the Central Nervous System (neuroleptics), a group of symptoms called Neuroleptic Malignant Syndrome, a potentially life-threatening condition, may occur. It is characterised by increased body temperature (hyperthermia), muscle rigidity, marked reduction in movement (akinesia), autonomic disturbances such as irregular pulse (palpitations) and blood pressure, sweating, tachycardia (increased heart rate), arrhythmia (irregular heartbeat), and altered mental status, which may progress to stupor and coma. Cases with atypical features such as loss of muscle rigidity or increased muscle tone (hypertonia) and low-grade fever may also occur.

Stroke:
Sereprile should be used with caution in patients with risk factors for cerebrovascular disorders (stroke), as an increased risk of such conditions has been observed.

Elderly patients with dementia:
In elderly patients with dementia, the risk of death is increased. In most cases, this appears to be due to heart and blood circulation problems (e.g. heart failure, where the heart's function is insufficient to ensure adequate blood supply to the body), sudden death, or infections (e.g. pneumonia).

Venous thromboembolism (VTE), a disorder of the circulatory system
Cases of blood clot formation in veins (venous thromboembolism, VTE) have been reported with antipsychotic medicines.
Since patients treated with antipsychotics often have risk factors for VTE, your doctor will identify all possible risk factors for VTE before and during treatment with Sereprile and take preventive measures.

Breast tumour
Sereprile may increase a hormone acting on the breast (prolactin). If you or a family member has had breast cancer during treatment with Sereprile, your doctor will monitor you closely.

Children and adolescents
In children, the efficacy and safety of tiapride have not been extensively studied. Therefore, your doctor will prescribe Sereprile with particular caution if it is for a child.

Other medicines and Sereprile
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, take care and consult your doctor if you are taking:

• medicines acting on the nervous system such as sedatives or tranquillisers (neuroleptics);

• levodopa, a medicine used to treat Parkinson's disease, or other Parkinson's disease treatments such as cabergoline, quinagolide, amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, and selegiline, because Sereprile may counteract their effect;

• medicines used to treat heart rhythm disorders, e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bepridil, bisoprolol, carvedilol, metoprolol, nebivolol, esmolol, diltiazem, verapamil, guanfacine, clonidine (used to treat high blood pressure), digitalis (to improve the heart's pumping strength), pilocarpine (to treat dry mouth and eyes), cholinesterase inhibitors;

• diuretics (medicines that reduce blood pressure), stimulant laxatives, intravenous amphotericin B (to treat fungal infections), glucocorticoids (anti-inflammatory agents), tetracosactide (to treat severe epilepsy);

• certain medicines for mental disorders (neuroleptics) (e.g. sulpiride, pipotiazine, sertindole, veralipride, chlorpromazine, levomepromazine, trifluoperazine, ciamemazine, sulpiride, pimozide, haloperidol, droperidol, fluphenazine, pipamperone, flupentixol, zuclopentixol, thioridazine);

• certain antiparasitic medicines (e.g. halofantrine, lumefantrine, pentamidine);

• antibiotic medicines (used to treat bacterial infections) such as intravenous erythromycin, intravenous spiramycin, moxifloxacin, sparfloxacin, cisapride (for gastrointestinal disorders), difemanil (for muscle contractions caused by spasm), mizolastine (for allergies), intravenous vincamine (to increase cerebral blood flow), imipramine and other antidepressants, lithium (used to treat psychotic disorders);

• methadone (for severe pain or opioid dependence);

• morphine derivatives (analgesics, antitussives, and opioid therapy), antihistamines (used for allergies), barbiturates (for epilepsy), benzodiazepines (used for anxiety and insomnia), antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), anaesthetics, analgesics (painkillers), other medicines such as baclofen (a muscle relaxant), thalidomide (an anticancer agent), pizotifen (used for headaches);

• nitrate derivatives and related compounds (used to dilate blood vessels).

Sereprile and alcohol
Alcohol increases the sedative effect of Sereprile. Avoid consuming alcoholic beverages and medicines containing alcohol. Drinking alcohol while taking Sereprile may also cause an electrolyte imbalance (imbalance of minerals in the blood), which may lead to QT interval prolongation (a heart rhythm disorder) (see "Warnings and precautions").

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Sereprile is not recommended during pregnancy and in women of childbearing age who are not using an effective method of contraception.
Do not take Sereprile during pregnancy unless specifically instructed by your doctor, who may decide to continue treatment throughout pregnancy if necessary.
Neuroleptic medicines of the same class as Sereprile, when administered by injection in emergency situations, may cause maternal hypotension (low blood pressure).
If Sereprile is taken during pregnancy, the newborn may experience adverse effects and should be adequately monitored by a doctor.
If you take Sereprile during the last three months of pregnancy, your newborn may experience:

• increased heart rate (tachycardia);
• exaggerated response to psychological or emotional stimuli (hyperexcitability);
• abdominal swelling (abdominal distension);
• delayed first bowel movement (meconium);
• excessive calmness (sedation);
• agitation, hypertonia and hypotonia (increased and decreased muscle tone), tremor, drowsiness, respiratory distress (breathing problems), feeding difficulties. Contact your doctor if your baby shows any of these symptoms.

Breastfeeding
You must not breastfeed while taking Sereprile. Ask your doctor about the best way to feed your baby while taking Sereprile.

Fertility
Sereprile may cause absence of menstruation and lack of ovulation, and may reduce human fertility (see "Possible side effects").

Driving and using machines
Even when used as directed by your doctor, Sereprile may cause excessive calmness (sedation), thus impairing your ability to drive or operate machinery (see "Possible side effects").
Sereprile injectable solution contains less than 1 mmol (23 mg) of sodium per maximum daily dose (corresponding to 8 vials), i.e. it is practically "sodium-free".

3. How to take Sereprile

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
The duration of treatment must not exceed 28 days.
The dose may vary and should be adjusted individually for each patient.
If you are an adult and suffer from acute alcoholism: the recommended dose is up to 4–8 ampoules per day (one ampoule every 4–6 hours); in chronic alcoholism manifestations, 1–2 tablets per day.
If you are elderly and suffer from behavioural disorders: the initial dose is 100 mg per day. The dose may be gradually increased, as necessary, up to a maximum of 300 mg per day.
If you suffer from severe chorea in Huntington's disease: the recommended dose is 3 tablets or 3 ampoules per day, depending on the severity of symptoms. This dosage may be increased up to 6 tablets or 6 ampoules per day.
Use in the elderly
If you are elderly, your doctor will carefully assess the recommended dose and may consider reducing it, especially if you have kidney problems.
If you take more Sereprile than you should
In case of overdose, symptoms may include: excessive drowsiness and calmness (sedation), coma, low blood pressure (hypotension), and extrapyramidal symptoms (movement disorders, rigidity, tremors).
Fatal outcomes have been reported, mainly in association with other psychotropic medicines used to treat psychiatric disorders.
If you forget to take Sereprile
Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Common side effects (may affect up to 1 in 10 people)

• increase in blood prolactin levels which may cause further disturbances. Therefore, breast pain, breast enlargement and excessive and persistent milk secretion from the breast (gynecomastia, galactorrhea), menstrual disorders or absence of menstruation (dysmenorrhea, amenorrhea) in women, erectile dysfunction/orgasm disorders may unusually occur in men
• feeling of intense tiredness (asthenia)
• fatigue
• dizziness and vertigo
• headache
• symptoms typical of Parkinson's disease: tremor, muscle rigidity, increased muscle tone (hypertonia), movement disorders (hypokinesia) and increased saliva production (hypersalivation). These symptoms are generally reversible after administration of an anticholinergic (e.g. biperiden)
• somnolence
• sedation
• insomnia
• agitation
• indifference.

Uncommon side effects (may affect up to 1 in 100 people)

• weight gain
• psychomotor restlessness known as "akathisia"
• early dyskinesia, dystonia such as muscle spasms, torticollis, deviation of gaze (oculogyric crises), jaw muscle contraction (trismus). These symptoms are generally reversible after administration of an anticholinergic (e.g. biperiden)
• absence of menstruation (amenorrhea)
• confusion, hallucinations
• syncope, seizures
• low blood pressure, generally when standing
• constipation (stipsis)
• skin redness (including redness with blisters)
• venous thromboembolism and deep vein thrombosis.

Rare side effects (may affect up to 1 in 1,000 people)

• severe movement disorders (acute dyskinesia)
• loss of consciousness
• reduction in white blood cell count (leukopenia), reduction in neutrophil count, a type of white blood cell (neutropenia), and reduction in granulocyte count, a type of white blood cell (agranulocytosis)
• decreased sodium levels in blood (hyponatremia), a condition called syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• after prolonged treatment (beyond 3 months), a condition called "tardive dyskinesia" has been reported, as with all medicines used to treat psychiatric disorders (neuroleptics). This is characterized by involuntary rhythmic movements, especially of the tongue and/or facial muscles. If these movement disorders occur, inform your doctor immediately, who will decide on the necessary measures. Antiparkinson medicines must not be used as antidotes, as they are ineffective or may worsen symptoms
• as with all neuroleptics, Neuroleptic Malignant Syndrome may occur, which is a potentially life-threatening complication (see "Warnings and precautions")
• cardiac conduction disorders (QT prolongation) and severe cardiac arrhythmias (such as torsades de pointes, ventricular tachycardia), and even ventricular fibrillation or cardiac arrest and sudden death (see "Warnings and precautions" and "Other medicines and Sereprile")
• blood clots in blood vessels, especially in the legs (with leg swelling, pain and redness), which may travel through blood vessels to the lungs causing chest pain and breathing difficulties. If you notice any of these symptoms, contact your doctor immediately (see "What you need to know before taking Sereprile"). Sometimes pulmonary embolism can be fatal
• pneumonia caused by food particles or vomit entering the lungs (aspiration pneumonia)
• reduced ability to breathe, e.g. reduced breathing rate and depth (respiratory depression), especially when taking other central nervous system depressant medicines
• intestinal obstruction, ileus
• increased liver enzymes in blood
• urticaria (allergic reaction)
• increased levels in blood of a substance produced by the body indicating possible muscle damage (elevated CPK), muscle weakness and/or muscle pain due to muscle breakdown (rhabdomyolysis)
• breast enlargement
• breast pain
• excessive and persistent milk secretion from the mammary gland (galactorrhea)
• gynecomastia
• impotence.

Side effects with unknown frequency (frequency cannot be estimated from the available data)

• withdrawal syndrome in the newborn, extrapyramidal disorders (such as rigidity, muscle spasms)
• falls.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sereprile

Sereprile 100 mg tablets
Store below 30°C.
Sereprile 100 mg/2 ml injectable solution
This medicinal product does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "exp".
The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sereprile contains
Sereprile 100 mg tablets

• The active substance is tiapride. Each tablet contains 111.1 mg of tiapride hydrochloride equivalent to 100 mg of tiapride base.
• The other components are mannitol, microcrystalline cellulose, povidone, anhydrous colloidal silica, magnesium stearate.

Sereprile 100 mg/2 ml injection solution

• The active substance is tiapride. Each 2 ml vial contains 111.1 mg of tiapride hydrochloride equivalent to 100 mg of tiapride base.
• The other components are sodium chloride, water for injections.

Description of the appearance of Sereprile and package contents
Sereprile is available as:

• divisible tablets, pack containing 20 divisible tablets
• injection solution, pack containing 10 vials with 2 ml of solution for intramuscular and intravenous use.

Marketing Authorization Holder
Sanofi S.r.l. – Viale L. Bodio, 37/B - Milan
MANUFACTURER
Sereprile 100 mg tablets
Delpharm Dijon - 6, Boulevard de l’Europe, Quétigny (France).
or
Famar Health Care Services Madrid, S.A.U. - Avda. Leganés, 62 - 28923 Alcorcón, Madrid (Spain)
Sereprile 100 mg/2 ml injection solution
Delpharm Dijon - 6, Boulevard de l’Europe, Quétigny (France).