SEREPRILE 100 mg Tablets

Зміст інструкції

1. Sereprile 100 mg tablets, 100 mg/2 ml injectable solution
   1. What is Sereprile and what is it 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

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

tiapride

Read this leaflet carefully before you start to take this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell 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 you take 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 is Sereprile and what is it 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 alterations in muscle coordination and leads to memory and learning disorders
(cognitive decline) and psychiatric problems.
This medicine is used to treat some behavioral disorders caused by alcohol consumption.
This medicine is used to treat some behavioral disorders in elderly patients.

2. What you need to know before taking Sereprile

Do not take Sereprile:

• if you are allergic to tiapride or any of the other ingredients of this medicine (listed in section 6);
• if you have a condition called “prolactin-dependent tumor” (e.g. prolactinoma of the pituitary gland);
• if you have breast cancer;
• if you have a tumor (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.
Tell your doctor immediately:

• if you develop fever and/or muscle rigidity while taking Sereprile, especially if you are already

taking any other medicine for the treatment of mental health.

• if you have or have had problems with alcohol (see “Sereprile with alcohol”).

Take special care before taking Sereprile:

• if you have Parkinson's disease. In this case, Sereprile should only be used in exceptional cases;
• if you suffer from epilepsy. While being treated with Sereprile, you may be subject to more frequent seizures; your doctor will need to monitor you closely;
• if you suffer from impaired kidney function (renal insufficiency), your doctor will reduce the dose because the use of Sereprile may cause loss of consciousness (coma) due to overdose (see “How to take Sereprile” and “If you take more Sereprile than you should”);
• if you suffer from severe heart or blood circulation disorders (cardiovascular and hemodynamic conditions), especially if you suffer from low blood pressure (hypotension);
• if you are elderly, because the use of Sereprile may cause a lowering of blood pressure (hypotension), a decrease in consciousness and coma.

During therapy with Sereprile, a disease that causes a severe decrease in white blood cells in the blood (severe neutropenia) may occur. In this case, your doctor will stop the use of Sereprile until your white blood cells return to normal levels.
Decreases in some types of blood cells (leukopenia, neutropenia and agranulocytosis) have been reported with the use of medicines of the same class as Sereprile (antipsychotics). Unexplained infections or fever may indicate an alteration in the composition of the blood (hematologic dyscrasia - see “Possible side effects”), which requires an immediate blood test.
If you are receiving Sereprile injections, especially intravenously, you may experience cases of decreased blood volume (hypovolemia) or sudden drops in blood pressure when you stand up or exert yourself (orthostatic hypotension).
Tiapride can induce a heart condition called "prolongation of the QT interval" which increases the risk of heart rhythm disturbances (severe ventricular arrhythmia, such as torsade de pointes; see “Possible side effects ”). Before taking Sereprile, your doctor will check the condition of your heart to check for factors that could increase the risk of rhythm disturbances, such as:

• if you suffer from a condition that causes a decrease in heart rate (bradycardia, with less than 55 beats per minute);
• if you suffer from an imbalance of certain substances in the blood (electrolytes), in particular a decrease in potassium in the blood (hypokalemia);
• if you have congenital heart rhythm abnormalities (congenital prolongation of the QT interval);
• if you have ongoing treatments with medicines that produce:
• decreased heart rate (bradycardia);
• imbalance of certain substances in the blood (electrolytes);
• alterations in heart function (decreased intracardiac conduction or prolongation of the QT interval; see “Other medicines and Sereprile”).

The doctor will check the condition of your heart, especially if you have other heart or blood circulation (cardiovascular) diseases or other family members with “prolongation of the QT interval”.
As with other medicines that act on the Central Nervous System (neuroleptics), a set of disorders called Neuroleptic Malignant Syndrome may occur, a potentially life-threatening complication, characterized by increased body temperature (hyperthermia), muscle rigidity, significant decrease in movements (akinesia), vegetative disorders such as irregularity of the pulse (palpable heartbeat) and blood pressure, sweating, tachycardia (increased heart rate), arrhythmia (alteration of the heart rhythm), changes in consciousness, which can progress to stupor and coma. Cases with atypical features such as loss of muscle rigidity or increased muscle tone (hypertonia) and low fever may occur.

Stroke:
Sereprile should be used with caution in patients with risk factors for brain blood circulation disorders (stroke), because an increased risk of these disorders has been observed.

Elderly patients with a syndrome leading to a progressive reduction in mental functions

(dementia):
In elderly patients with dementia, the risk of death increases and, in most cases, seems to be due to heart and blood circulation problems (e.g. heart failure, the functionality of your heart is insufficient to ensure adequate blood supply to the body), sudden death or caused by infections (e.g. pneumonia).

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

Breast cancer
Sereprile may increase a hormone that acts on the breast (prolactin). If you or a family member have had breast cancer during therapy with Sereprile, your doctor will monitor you.

Children and adolescents
The efficacy and safety of tiapride have not been extensively studied in children: therefore, your doctor will prescribe Sereprile with particular attention 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, be careful and consult your doctor if you are taking:

• medicines that act on the nervous system such as sedatives or tranquilizers (neuroleptics);
• levodopa, a medicine used to treat Parkinson's disease, medicines used to treat Parkinson's disease 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, for example quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, bepridil, bisoprolol, carvedilol, metoprolol, nebivolol, esmolol, diltiazem, verapamil and guanfacine, clonidine (used to treat high blood pressure), digitalis (to improve the heart's pumping force), pilocarpine (to treat dry mouth and eyes), cholinesterase inhibitors;
• diuretics (medicines that reduce blood pressure), stimulant laxatives, amphotericin B administered by injection (for the treatment of fungal infections), glucocorticoids (anti-inflammatory drugs), tetracosactides (for the treatment of severe epilepsy);
• some medicines for the treatment of mental disorders (neuroleptics) (e.g. sultopride, pipothiazine, sertindole, veralipride, chlorpromazine, levomepromazine, trifluoperazine, ciamemazine, sulpiride, pimozide, haloperidol, droperidol, fluphenazine, pipamperone, flupentixol, zuclopentixol, thioridazine);
• some medicines for the treatment of parasitic infections (e.g. alofantrine, lumefantrine, pentamidine);
• antibiotic medicines (medicines used to treat infections caused by bacteria) such as

erythromycin, administered by injection, spiramycin administered by injection,
moxifloxacin and sparfloxacin, cisapride (for the treatment of gastric disorders), difemanil (for
the treatment of muscle contractions caused by spasm), mizolastine (for the treatment
of allergies), vincamine administered by injection (to increase blood flow to the
brain), imipramine and other medicines for the treatment of depression, lithium (used to treat
psychotic disorders);

• methadone (for the treatment of severe pain or to counteract drug addiction);
• morphine derivatives (analgesics, antitussives and opioid therapy), antihistamines (medicines used for allergies), barbiturates (medicines for epilepsy), benzodiazepines (medicines used for anxiety and insomnia therapy), antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), anesthetics, analgesics (pain relievers), other medicines such as baclofen (a muscle relaxant), thalidomide (an antitumor drug), pizotifen (used for headaches);
• nitrate derivatives and related compounds (used to dilate blood vessels).

Sereprile with alcohol
Alcohol increases the sedative effect of Sereprile. Avoid taking alcoholic beverages and medicines containing alcohol at the same time. Alcohol consumption while taking Sereprile can also cause an electrolyte imbalance (imbalance of minerals in the blood) which can cause a prolongation of the QT interval (heart rhythm and rate disorder) (see “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Sereprile is not recommended during pregnancy and in women of childbearing potential who are not using effective contraception.
Do not take Sereprile if you are pregnant, unless expressly indicated by your doctor who, if necessary, may continue therapy throughout pregnancy.
Neuroleptic medicines (neuroleptics) administered by injection, which are used in emergency situations, can cause a lowering of maternal blood pressure (hypotension).
If Sereprile is taken during the last three months of pregnancy, your newborn may experience:

• increased heart rate (tachycardia);
• exaggerated reaction to psychic or emotional stimuli (hyperexcitability);
• swelling of the abdomen (abdominal distension);
• delay in the first bowel movement (meconium);
• excessive calmness (sedation);
• agitation, hypertonia and hypotonia (increased and decreased muscle tone), tremor, drowsiness, respiratory distress (breathing problems), feeding disorders. Contact your doctor if your baby presents any of these symptoms.

Breastfeeding
You should not breastfeed while taking Sereprile. Ask your doctor what is the best way to breastfeed your baby while taking Sereprile.
Fertility
Sereprile may lead to absence of the menstrual cycle and lack of ovulation and may decrease human fertility (see “Possible side effects”).

Driving and using machines
Even if used as advised by your doctor, Sereprile may cause excessive calmness (sedation), so the ability to drive vehicles and use machinery may be impaired (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 following exactly the instructions of your doctor or pharmacist. If you have doubts
consult your doctor or pharmacist.
The duration of treatment should not exceed 28 days.
The dose may vary and must be adapted to each patient.

If you are an adult, and suffer from acute alcoholism: the recommended dose is up to 4-8 vials per day (one vial every
4-6 hours); in manifestations of chronic alcoholism 1-2 tablets per day.

If you are elderly, and suffer from behavioral disorders: the initial dose is 100 mg per day. The dose
may be gradually increased up to a maximum of 300 mg per day, as needed.

If you suffer from severe chorea in Huntington's disease: the recommended dose is 3 tablets or 3 vials per
day, depending on the severity of the disorders. This dosage may be increased up to 6 tablets or 6 vials
per day.

Use in the elderly
If you are elderly, your doctor will carefully assess the recommended dose and must evaluate a possible reduction
of the dose, especially if you have kidney problems.

If you take more Sereprile than you should
In case of overdose, you may experience disorders such as: drowsiness and excessive calmness (sedation), coma,
lowering of blood pressure (hypotension) and extrapyramidal symptoms (movement disorder, rigidity,
tremors).
Fatal outcomes have been reported, mainly in association with other medicines called "psychotropic" used for
treating mental disorders.

If you forget to take Sereprile
Do not take a double dose to make up for a missed dose.
If you have any doubts about the use of this medicine, ask 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 prolactin levels in the blood which may cause other disorders. Therefore, breast pain, breast enlargement and excessive and continuous milk production 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 fatigue (asthenia)
• tiredness
• 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 (for example, biperiden)

• drowsiness
• sedation
• insomnia
• agitation
• indifference.

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

• weight gain
• psychomotor syndrome called "akathisia"
• early dyskinesia, dystonia such as muscle spasms, torticollis, deviations of the gaze (oculogyric crises), contraction of the muscles of the jaw (trismus). These symptoms are generally reversible after administration of an anticholinergic (for example, biperiden)
• absence of menstruation (amenorrhoea)
• confusion, hallucinations
• syncope, convulsions
• low blood pressure, generally when standing up
• constipation
• skin redness (including that with redness or blisters)
• venous thromboembolism and deep vein thrombosis.

Rare side effects (may affect up to 1 in 1000 people)

• serious movement disorders (acute dyskinesia)
• loss of consciousness
• reduction in the number of white blood cells (leukopenia), reduction in the number of neutrophils, a type of white blood cells (neutropenia) and reduction in the number of granulocytes, a type of white blood cells (agranulocytosis)
• decrease in sodium in the blood (hyponatremia), a condition called inappropriate secretion of the antidiuretic hormone syndrome (SIADH)
• after a prolonged period of treatment (more than 3 months), a condition called “tardive dyskinesia” has been reported, as with all medicines used to treat psychological disorders (neuroleptic agents). This is characterized by involuntary rhythmic movements especially of the tongue and/or facial muscles. If these movement disorders occur, you should immediately inform your doctor, who will decide the necessary measures. Medicines for Parkinson's disease should not be used as an antidote, because they are ineffective or may worsen the symptoms
• as with all neuroleptics, Neuroleptic Malignant Syndrome may occur, which is a potentially fatal complication (see “Warnings and precautions ”)
• disturbances in cardiac conduction (QT prolongation) and serious 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 swelling, pain and redness of the legs) which can move through the blood vessels to the lungs causing chest pain and difficulty breathing. 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)
• decreased ability to breathe, e.g. decrease in the number of breaths and the depth of breathing (respiratory depression) when taking other medicines, depressants of the Central Nervous System
• intestinal obstruction, ileus
• increase in blood liver enzymes
• urticaria (allergic reaction)
• increase in blood of a substance produced by the body that indicates possible muscle damage (elevated CPK), muscle weakness and/or muscle pain due to muscle destruction (rhabdomyolysis)
• breast enlargement
• breast pain
• excessive and continuous milk production from the mammary gland (galactorrhea)
• gynecomastia
• impotence.

Side effects with unknown frequency (frequency cannot be estimated on the basis of the available data)

• neonatal withdrawal syndrome, extrapyramidal disorders (such as rigidity, muscle spasms)
• falls.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through 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 at a temperature below 30°C.
Sereprile 100 mg/2 ml injectable solution
This medicine 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 which is stated on the pack after "exp".
The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Sereprile contains
Sereprile 100 mg tablets

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

Sereprile 100 mg/2 ml injectable solution

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

Description of the appearance of Sereprile and contents of the pack
Sereprile is presented in the form of:

• divisible tablets, pack of 20 divisible tablets
• injectable solution, pack containing 10 ampoules of 2 ml injectable solution for intramuscular and intravenous use.

Marketing Authorisation 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 injectable solution
Delpharm Dijon - 6, Boulevard de l’Europe, Quétigny (France).