DENIBAN

Package leaflet: Information for the patient

DENIBAN 50 mg tablets

amisulpride
Please read all of 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 adverse reactions, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Deniban is and what it is used for

Deniban contains amisulpride, which belongs to a class of medicines called "Psycholeptics,
benzamides".
Deniban is indicated for the treatment (short to medium term) of mental disorders arising from a severe disturbance of affective tone, characterized by states of pessimism or depression (dysthymia).

2. What you should know before taking Deniban

Do not take Deniban:

• if you are allergic to amisulpride or any of the other ingredients of this medicine (listed in section 6);

• if you have a tumor of the gland located above the kidneys (pheochromocytoma);

• if you have breast cancer (mammary tumor) or a disorder called "prolactin-dependent tumor";

• if you are a child; Deniban must not be taken before completion of the developmental stage (puberty);

• if you are taking any of the following medicines, because they may cause serious disturbances in heart rhythm (onset of torsades de pointes):

• medicines used to treat irregular heartbeat such as:

  • class Ia antiarrhythmics like quinidine, disopyramide;
  • class III antiarrhythmics like amiodarone, sotalol;

• other medicines such as bepridil (for treatment of irregular heartbeat), cisapride (for treatment of gastrointestinal disorders), sultopride, thioridazine (for treatment of mental disorders), methadone administered by injection (for treatment of severe pain or to counteract opioid dependence), vincamine administered by injection (to increase blood flow to the brain), halofantrine (for treatment of malaria),
  erythromycin, pentamidine, sparfloxacin (for treatment of bacterial infections)
  (see "Other medicines and Deniban");

• levodopa, a medicine used to treat Parkinson's disease (see "Other medicines and Deniban").

Warnings and precautions
Talk to your doctor or pharmacist before taking Deniban.
Pay particular attention before taking Deniban, especially if:

• you are elderly, as you may be more likely to experience low blood pressure and drowsiness. A dose reduction may also be required in case of renal impairment;
• you suffer from impaired kidney function, as your doctor will reduce your dose or prescribe intermittent treatment ("How to take Deniban");
• you have epilepsy. During treatment with Deniban, you may experience more frequent seizures. Therefore, your doctor will monitor you during treatment;
• you have Parkinson's disease, as this medicine could worsen your condition;
• you have hyperglycemia. Therefore, patients with a confirmed diagnosis or risk factors for diabetes should undergo appropriate monitoring of blood sugar levels.

With antipsychotic medicines, including Deniban, decreases in certain types of white blood cells in the blood (leukopenia, neutropenia, and agranulocytosis) have been reported. Unexplained infections or fever may indicate a blood disorder (hematologic dyscrasia - see "Possible side effects"), requiring immediate blood tests.
As with other medicines acting on the Central Nervous System, a group of symptoms known as Neuroleptic Malignant Syndrome, a potentially life-threatening condition, may occur. It is characterized by hyperthermia (increased body temperature), muscle rigidity, akinesia (movement disorders), irregular heartbeat and blood pressure, sweating, increased heart rate, heart rhythm abnormalities, elevated creatine phosphokinase levels (a substance produced by the body indicating possible muscle damage), rhabdomyolysis (muscle damage), and disturbances in consciousness that may progress to stupor and coma.
If you develop high body temperature, particularly when daily doses are high, your doctor will discontinue any antipsychotic medicine, including Deniban.
Amisulpride causes a heart disturbance called "QT interval prolongation" (see "Possible side effects"), which increases the risk of heart rhythm disturbances (serious ventricular arrhythmias such as torsades de pointes). Your doctor will check your heart condition, especially if you have other cardiovascular diseases or family history of "QT interval prolongation". Concomitant therapy with other neuroleptic medicines should be avoided.
Deniban should be used with caution if risk factors for cerebrovascular disorders (stroke) are present.

Elderly patients with psychosis associated with dementia
In elderly patients with dementia, the risk of death is increased.

Venous thromboembolism (VTE)
Before and during treatment with Deniban, your doctor will perform checks to identify any risk factors for a circulatory system disorder called "venous thromboembolism".

Breast cancer
Deniban may increase levels of prolactin (a hormone acting on the breast). If you have a personal or family history of breast cancer, your doctor will monitor you during Deniban therapy.

Benign pituitary tumor
Deniban may increase levels of prolactin (a hormone acting on the breast). During Deniban treatment, cases of abnormal growth of a gland called the pituitary gland (benign pituitary tumor such as prolactinoma) have been observed. If you have very high levels of prolactin or clinical signs of pituitary tumor (such as visual field defects and headache), your doctor will perform appropriate checks. If a diagnosis of pituitary tumor is confirmed, your doctor will discontinue Deniban treatment.

After abrupt discontinuation of high therapeutic doses of antipsychotic medicines, withdrawal symptoms have been reported, including nausea, vomiting, and insomnia.
Psychiatric symptoms may also recur, and with Deniban, the onset of involuntary movement disorders (such as akathisia, dystonia, and dyskinesia) has been reported.
Therefore, your doctor will gradually discontinue Deniban.

Severe liver toxicity has been reported following the use of Deniban. Contact your doctor immediately if you experience fatigue, loss of appetite, nausea, vomiting, abdominal pain, or yellowing of the eyes and skin.

Children and adolescents
Deniban must not be given to children before puberty and is not recommended in any case until the age of 18 years.

Other medicines and Deniban
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The effects of Deniban may be influenced by, or may influence, the effects of the following medicines.
Combination with other medicines of the same class as Deniban (psychotropic drugs) requires particular caution and monitoring by your doctor to avoid unexpected adverse effects.
When drugs known as neuroleptics are administered concomitantly with drugs that "prolong the QT interval" (like Deniban), the risk of developing heart rhythm disturbances (cardiac arrhythmias) increases.

Contraindicated combinations

• Some medicines that may cause serious disturbances in heart rhythm (torsades de pointes) must not be used with Deniban. These include:
• medicines used to treat irregular heartbeat such as class Ia antiarrhythmics (e.g., quinidine, disopyramide) and class III antiarrhythmics (e.g., amiodarone, sotalol);
• other medicines such as bepridil (for treatment of irregular heartbeat), cisapride (for treatment of gastrointestinal disorders), sultopride, thioridazine (for treatment of mental disorders), methadone administered by injection (for treatment of severe pain or to counteract opioid dependence), vincamine administered by injection (to increase blood flow to the brain), halofantrine (for treatment of malaria), erythromycin, pentamidine, and sparfloxacin (for treatment of bacterial infections).
• levodopa, a medicine used to treat Parkinson's disease, as the effects of levodopa and Deniban may interact with each other.
• medicines classified as "dopamine agonists" such as bromocriptine and ropinirole (for treatment of Parkinson's disease), since Deniban may counteract their effect.
• medicines that may cause low potassium levels in the blood (hypokalemia), such as: potassium-wasting diuretics, stimulant laxatives, amphotericin B administered by injection (for treatment of fungal infections), glucocorticoids (for treatment of inflammatory disorders), tetracosactide (for treatment of a severe form of epilepsy). Low blood potassium levels should be corrected with appropriate medical treatment.

Not recommended combinations

• Medicines that may cause serious disturbances in heart rhythm (increase the risk of torsades de pointes or may prolong the QT interval):
• medicines that may reduce heart rate: beta-blockers, calcium channel blockers such as diltiazem, verapamil, guanfacine, clonidine (for treatment of high blood pressure), and digitalis (to improve the heart's pumping strength);
• medicines with strong sedative effects on the nervous system (neuroleptics such as pimozide, haloperidol), antidepressants (tricyclics, lithium);
• some medicines for treatment of allergies (antihistamines);
• some medicines for treatment of malaria (e.g., mefloquine).

Combinations requiring caution

• medicines acting on the Central Nervous System (including: hypnotics, tranquilizers, anesthetics, analgesics, sedative H1 antihistamines), medicines that calm, induce sleep, or relax muscles (barbiturates, benzodiazepines, and other anxiolytics).
• medicines to regulate blood pressure (antihypertensives, such as clonidine and its derivatives, and other antihypertensive medicines).
• clozapine, as it may lead to increased levels of amisulpride in the blood.

Deniban and alcohol
Deniban may increase certain disturbances caused by alcohol.

Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, if you suspect you may be pregnant, or if you are planning pregnancy, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Do not take Deniban if you are pregnant, suspect you are pregnant, or if you are of childbearing age and not using effective contraception.
If you have taken Deniban during the last three months of pregnancy, the baby may show symptoms such as agitation, increased muscle tone, involuntary tremors, drowsiness, breathing problems, or difficulty feeding.
If your baby shows any of these symptoms, contact your doctor.

Breastfeeding
You must not breastfeed while taking Deniban. Consult your doctor if you are taking Deniban.

Driving and using machines
Deniban may cause drowsiness and blurred vision, and therefore may impair your ability to drive vehicles or operate machinery (see "Possible side effects").

Deniban tablets contain lactose.
If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to take Deniban

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one 50 mg tablet daily, or as otherwise prescribed by your doctor.

Use in the elderly
If you are elderly, your doctor will carefully evaluate the recommended dose, as there may be an increased risk of low blood pressure (hypotension) and excessive drowsiness (sedation). If necessary, your doctor may consider reducing the dose, particularly in patients with kidney problems.

Children and adolescents
Deniban must not be given to children before puberty.
The use of Deniban from puberty up to the age of 18 years is not recommended.

Impaired renal function (renal insufficiency)
Your doctor will prescribe a lower dose depending on the degree of renal impairment.

If you take more Deniban than you should
If you have taken more Deniban than prescribed, you may experience drowsiness or sedation, low blood pressure (hypotension), tremors, rigidity, increased salivation, movement disorders (extrapyramidal symptoms), and coma.
Fatal cases have been reported, particularly when associated with other medicines for mental disorders (psychotropic agents).
In case of accidental overdose of Deniban, contact your doctor immediately or go to the nearest hospital.

If you forget to take Deniban
Do not take a double dose to make up for the missed dose.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Deniban can cause side effects, although not everyone experiences them.

Very common (may affect more than 1 in 10 people)

• tremor
• rigidity
• slowing down or reduction of spontaneous body movements (hypokinesia)
• increased salivation (hypersalivation)
• feeling of restlessness (akathisia)
• movement disorders (dyskinesia)
  These disorders are generally mild at the recommended doses and partially reversible with administration of anti-Parkinson's medications, even without discontinuing Deniban.

Common (may affect up to 1 in 10 people)

• muscle cramps, especially in the neck (spasmodic torticollis), eyes (oculogyric crisis), and jaw (trismus), which are reversible with appropriate medications prescribed by a doctor, even without discontinuing Deniban therapy
• drowsiness or insomnia
• anxiety
• agitation
• psychomotor excitability
• orgasm abnormalities
• blurred vision (see "Driving and use of machines")
• heart rhythm disturbances (QT prolongation)
• constipation (stippsis)
• nausea
• vomiting
• dry mouth
• difficulty in digestion (dyspepsia)
• increased levels of a hormone in the blood called prolactin, which may cause:
  • unusual milk production in women and men (galactorrhea)
  • absence of menstruation (amenorrhea)
  • breast enlargement in men (gynecomastia)
  • breast pain (mastodynia)
  • erectile dysfunction
    These disorders disappear after discontinuation of Deniban therapy.
• low blood pressure (hypotension)
• weight gain

Uncommon (may affect up to 1 in 100 people)

• decrease in certain types of blood cells (leucopenia, neutropenia)
• movement disorders, including uncontrollable movements of the tongue, mouth, and face (tardive dyskinesia). These may occur during or after prolonged treatment
• seizures
• elevated blood sugar levels
• slowed heart rate (bradycardia)
• palpitations
• increased levels of liver enzymes (particularly transaminases)
• allergic reactions
• increased triglycerides and cholesterol in the blood (hypertriglyceridemia and hypercholesterolemia)
• confusion
• increased blood pressure
• nasal congestion
• aspiration pneumonia (mainly in association with other psychotropic drugs and central nervous system-acting agents)
• osteopenia and osteoporosis (increased bone fragility)
• inability to completely empty the bladder (urinary retention)
• liver tissue damage (hepatocellular injury)

Rare (may affect more than 1 in 1,000 people)

• decrease in certain types of blood cells (agranulocytosis)
• benign pituitary tumour such as prolactinoma
• reduced sodium concentration in plasma (hyponatremia), inappropriate secretion of antidiuretic hormone (SIADH)
• combination of fever, rapid breathing, sweating, muscle rigidity, and reduced level of consciousness associated with a serious condition known as "neuroleptic malignant syndrome", sometimes fatal (see "Warnings and precautions")
• heart rhythm disturbances (QT interval prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest and sudden death) (see "Warnings and precautions")
• blood clots in veins (venous thromboembolism, including potentially fatal pulmonary embolism and deep vein thrombosis)
• rapid swelling of legs, arms, face, or tongue (angioedema)
• urticaria

Frequency not known (frequency cannot be estimated from available data)

• withdrawal symptoms in newborns of mothers who took Deniban (neonatal withdrawal syndrome, extrapyramidal disorders)
• uncomfortable sensation in the legs temporarily relieved by movement, with symptoms worsening in the evening (restless legs syndrome)
• increased sensitivity of the skin to sunlight and ultraviolet rays (photosensitivity reaction)
• falls due to impaired body balance, which may result in fractures
• rhabdomyolysis (muscle breakdown associated with muscle pain)
• elevated levels of creatine phosphokinase (a blood test indicating muscle damage)

Mild chills, breathing difficulties (dyspnea), and muscle pain have also been observed.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at the website:
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 Deniban

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 stated on the carton and on the blister 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 no longer required. This will help protect the environment.

6. Package contents and other information

What Deniban contains
Deniban 50 mg tablets

• The active substance is amisulpride. Each tablet contains 50 mg of amisulpride.
• The other components are: sodium carboxymethyl starch (type A), monohydrate lactose, microcrystalline cellulose, hypromellose, magnesium stearate.

Description of the appearance of Deniban and contents of the pack
Deniban 50 mg tablets are available as tablets:

• Pack size: 12 tablets.

Marketing Authorization Holder
Sanofi S.r.l. – Viale L. Bodio, 37/B - Milan
Manufacturer
Delpharm Dijon – 6, Boulevard de l’Europe, 21800 Quétigny - France