AMISULPRIDE MYLAN

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
AMISULPRIDE
Available from:
McDermott Laboratories Ltd t/a Gerard Laboratories
ATC code:
N05AL05
INN (International Name):
AMISULPRIDE
Dosage:
200 Milligram
Pharmaceutical form:
Tablets
Prescription type:
Product subject to prescription which may be renewed (B)
Therapeutic area:
amisulpride
Authorization status:
Not Marketed
Authorization number:
PA0577/125/003
Authorization date:
2009-08-28

PACKAGE LEAFLET

Package leaflet: information for the patient

Amisulpride Mylan 50 mg and 200 mg Tablets

amisulpride

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

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 only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet:

What Amisulpride Mylan is and what it is used for

What you need to know before you take Amisulpride Mylan

How to take Amisulpride Mylan

Possible side effects

How to store Amisulpride Mylan

Contents of the pack and other information

1.

What Amisulpride Mylan is and what it is used for

Amisulpride Mylan contains a medicine called amisulpride. This belongs to a group of medicines called

‘antipsychotics’. It is used in the treatment of acute and chronic schizophrenic disorders. This condition

causes symptoms such as becoming withdrawn, sensing, seeing or hearing things which do not exist,

mistaken beliefs or unfounded suspicions. Sometimes people with these symptoms may also feel tense,

anxious or depressed.

Amisulpride Mylan also acts on mood disorder in the sense of depression.

2.

What you need to know before you take Amisulpride Mylan

Do not take Amisulpride Mylan

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

if you notice signs of an allergic reaction including: a rash, swallowing or breathing problems,

swelling of your lips, face, throat or tongue

if you have a prolactin dependent tumour or breast cancer

if you have phaeochromocytoma (a tumour on the adrenal gland)

if you are breast-feeding (see Pregnancy and breast-feeding section)

- if you are taking levodopa (used to treat Parkinson's disease)

- if the patient is under 18 years old

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor or

pharmacist before taking Amisulpride Mylan.

Warnings and precautions

Talk to your doctor or pharmacist before taking Amisulpride Mylan if you:

are an elderly patient as elderly people are more likely to get low blood pressure and feel sleepy. A

small increase in the number of deaths of elderly people with dementia has been reported for

patients taking anti-psychotics compared to those not receiving anti-psychotics

or someone else in your family has a history of blood clots, as medicines like these have been

associated with formation of blood clots

or someone else in your family has a history of breast cancer, your doctor will carefully monitor you

as amisulpride can affect the risk of developing breast cancer

have kidney problems

have Parkinson’s disease (taking this medicine may worsen your condition)

have a history of fits (epileptic seizures)

have an abnormal heart rate or rhythm

have a slow heart beat (less than 55 beats per minute) or take medicines that can cause a lower heart

rate, your doctor will regularly monitor you

have heart disease or family history of heart problems

have diabetes mellitus or at risk of having it

have been told by your doctor that you are at risk of having stroke

have been told you have a low amount of potassium in your blood

have a low number of white blood cells (this means you may get infections more easily than usual)

have frequent infections such as fever, severe chills, sore throat or mouth ulcers. These could be signs

of a blood problem called leucopenia

have high levels of prolactin, a hormone produced by your pituitary gland.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking

Amisulpride Mylan.

Contact your doctor immediately if you suddenly develop a high temperature (please refer to section 4).

Children and adolescents

Amisulpride Mylan should not be given to children or adolescents under 18 years old.

Other medicines and Amisulpride Mylan

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, do not take this medicine and tell your doctor if you are taking:

Levodopa, a medicine to treat Parkinson’s disease

Drugs called dopamine agonists such as ropinirole and bromocriptine (medicines used to treat

Parkinson’s disease)

Amisulpride Mylan can interact with the following medicines:

Anaesthetics

Antihistamines (which cause drowsiness)

Medicines used to control your heart beat such as quinidine, disopyramide, amiodarone and sotalol

Other anti-psychotic medicines used for mental problems

Medicines for severe pain called opiates such as morphine or pethidine

Medicines for high blood pressure and heart problems such as diltiazem, verapamil, guanfacine and

digitalis

Clonidine used for migraines, flushing or high blood pressure

Medicines used to treat malaria such as mefloquine

Medicines which help you sleep such as barbiturates and benzodiazepines

Pain-killers such as tramadol and indometacin

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking

Amisulpride Mylan.

Please refer to “Do not take Amisulpride Mylan” in addition.

Amisulpride Mylan with alcohol

Do not drink alcohol while you are taking Amisulpride Mylan, it may make you drowsy.

Pregnancy and breast-feeding

Due to very limited clinical data, Amisulpride Mylan should not be taken during pregnancy and breast-

feeding.

The following symptoms may occur in newborn babies, of mothers that have used amisulpride 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.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Amisulpride Mylan may make you feel less alert, drowsy or sleepy while taking this medicine. If this

happens do not drive or operate machinery until you are sure that you are not affected.

Amisulpride Mylan contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before

taking this medicine.

3.

How to take Amisulpride Mylan

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or

pharmacist if you are not sure.

Adults:

Doses are adjusted individually and can range from 50 mg up to 800 mg daily. Your doctor may start you on

a lower dose if necessary. If necessary your doctor can prescribe up to 1200 mg each day. This will depend

on the nature of your illness and you should follow your doctor’s instructions carefully.

If you are taking up to 400 mg Amisulpride Mylan a day, you should take it in one dose. Take the dose at the

same time each day. If you are taking more than 400 mg Amisulpride Mylan a day, you should divide the

dose into two and take half in the morning and half in the evening.

Elderly:

Your doctor will need to keep a close check on you as you are more likely to have low blood pressure or

sleepiness due to this medicine.

People with kidney problems:

Your doctor may need to give you a lower dose.

Use in children and adolescents (under 18 years of age):

Amisulpride Mylan should not be given to children under 18 years old.

Amisulpride Mylan tablets can be administered independently from the meals. Take this medicine by mouth.

Tablets should be taken whole or halved with a sufficient amount of liquid. Do not chew your tablets.

The tablets can be divided into equal doses.

If you take more Amisulpride Mylan than you should

Contact your doctor or the hospital immediately. Take this medicine pack with you. This is so the doctor

knows what you have taken. The following effects may happen: feeling restless or shaky, rigid muscles,

feeling drowsy or sleepy which could lead to a loss of consciousness.

If you forget to take Amisulpride Mylan

Do not take a double dose to make up for a forgotten dose. Take your next dose at the usual time.

If you stop taking Amisulpride Mylan

Do not stop taking Amisulpride Mylan without consulting your doctor. Stopping treatment suddenly may

cause withdrawal effects such as feeling sick, vomiting, sweating, sleeplessness, extreme restlessness,

muscle stiffness or abnormal movements, or your original condition may come back.

If you have any further questions on 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.

If any of the following happen, stop taking Amisulpride Mylan and tell your doctor or go to your

nearest hospital emergency department immediately:

Uncommon (may affect up to 1 in 100 people):

you have an allergic reaction. The signs may include: an itchy, lumpy rash, swallowing or breathing

problems, swelling of your lips, face, throat or tongue

you have a fit (seizure).

Frequency not known (cannot be estimated from the available data):

your heart starts beating faster than usual which could result in heart attack or life-threatening heart

disorder.

you have high temperature, muscle stiffness, feeling faint or light-headed, confused, drowsy or

agitated, paleness, racing heart, fast breathing, changes to blood pressure, sweating, urinary

incontinence (these are symptoms of a very rare syndrome called Neuroleptic Malignant Syndrome).

you have blood clots in the veins specially in the legs (symptoms include swelling, pain and redness

in the leg), which may travel though blood vessels to the lungs causing chest pain and difficulty in

breathing.

Tell your doctor as soon as possible if you have any of the following side effects:

Very Common (may affect more than 1 in 10 people):

trembling, muscle stiffness or spasm, slow movement, producing more saliva than usual or feeling

restless.

Common (may affect up to 1 in 10 people):

movements that you cannot control, mainly of the arms and legs, head, neck, jaw or eyes

(These symptoms can be reduced if your doctor lowers your dose of amisulpride or prescribes an

additional medicine).

Uncommon (may affect up to 1 in 100 people):

movements that you cannot control, mainly of the face or tongue.

Frequency not known (cannot be estimated from the available data):

you get more infections than usual. This could be because of a blood disorder (agranulocytosis) or a

decrease in the number of white blood cells (neutropenia, leucopenia).

benign (non-cancerous) pituitary tumour such as prolactinoma.

withdrawal syndrome in newborns (see “Pregnancy and breast-feeding”).

Other side effects include:

Common (may affect up to 1 in 10 people):

difficulty sleeping (insomnia), drowsiness or feeling anxious or agitated

constipation, feeling or being sick, dry mouth

weight gain

difficulty reaching orgasm, problems getting or maintaining an erection

unusual secretion of milk from the breasts in women and men, breast pain

breast enlargement in men

menstrual period stops

low blood pressure (causing dizziness).

Uncommon (may affect up to 1 in 100 people):

high blood sugar levels (hyperglycaemia)

elevated liver enzymes

slowing of the heartbeat.

Not known (frequency cannot be estimated from the available data):

raised levels of certain fats (triglycerides) or cholesterol in the blood

confusion

low levels of sodium in your blood which may be seen in blood tests (hyponatraemia)

Feeling unwell, confused or weak, feeling sick (nausea), loss of appetite, feeling irritable. This could

be signs of an illness called syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not

listed in this leaflet. You can also report side effects directly via

HPRA Pharmacovigilance, Earlsfort

Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-

mail:medsafety@hpra.ie.

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Amisulpride Mylan

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage conditions.

Do not use Amisulpride Mylan after the expiry date which is stated on the blister and carton after EXP. The

expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Amisulpride Mylan contains

The active substance is amisulpride.

Each Amisulpride Mylan 50 mg tablet contains 50 mg amisulpride.

Each Amisulpride Mylan 200 mg tablet contains 200 mg amisulpride.

The other ingredients are: lactose monohydrate (see section 2, “Amisulpride Mylan contains lactose”),

methylcellulose, sodium starch glycolate (type A), microcrystalline cellulose, magnesium stearate.

What Amisulpride Mylan looks like and contents of the pack

Amisulpride Mylan 50 mg are white to off-white 6.0 mm round, bi-convex tablets with break line on one

side in PVC/Aluminium blister packs of 10, 12, 20, 30, 60 or 90 tablets.

Amisulpride Mylan 200 mg are white to off-white 11.0 mm round, flat tablets with break line on one side in

PVC/Aluminium blister packs of 10, 30, 60, 90, 120 or 150 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

McDermott Laboratories Ltd. t/a Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road,

Dublin 13, Ireland.

Manufacturer

McDermott Laboratories Ltd t/a Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road,

Dublin 13, Ireland

This medicinal product is authorised in the Member States of the EEA under the following names

Czech Republic

Amisulprid Mylan 50/100/200 mg tablety

Belgium

Amisulpride Mylan 50/100/200 mg tabletten

Bulgaria

Amisulgen 50/100/200 mg tablets

Ireland

Amisulpride Mylan 50/200 mg tablets

Greece

Amisulpride/Generics tablets 100 mg/tab

Hungary

Amisulpride Mylan 100/200 mg tabletta

Italy

Amisulpride Mylan Generics 50/100/200mg compresse

Portugal

Amissulprida Atirdrane

Slovak Republic

Amisulprid Mylan 100/200 mg

Slovenia

Amisulprid Mylan 100/200 mg tablete

Spain

Amisulprida Mylan Pharmaceuticals 100/200mg comprimidos EFG

This leaflet was last revised in 09/2016.

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Amisulpride Mylan 200 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 200 mg amisulpride.

Excipient with known effect:

Each tablet contains 100 mg lactose monohydrate

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet.

White to off-white 11.0 mm round, flat tablets with break line on one side.

The tablet can be divided into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Amisulpride Mylan is indicated for the treatment of acute and chronic schizophrenic disorders:

Positive symptoms with delusions, hallucinations, thought disorders, hostility and suspicious behavior.

Primarily negative symptoms (deficit syndrome) with blunted affect, emotional and social withdrawal.

Amisulpride Mylan also controls secondary negative symptoms in productive conditions as well as affective disorders

such as depressive mood or retardation.

4.2 Posology and method of administration

Posology:

For acute psychotic episodes the recommended oral dose ranges from 400 to 800 mg/day. In individual cases, the daily

dose may be increased up to 1200 mg/day. Doses above 1200 mg/day have not been extensively evaluated for safety

and therefore should not be used. No specific titration is required when initiating the treatment with Amisulpride

Mylan. Doses should be adjusted according to individual response. Maintenance treatment should be established

individually with the minimally effective dose.

For patients with mixed positive and negative symptoms, doses should be adjusted to obtain optimal control of positive

symptoms.

For patients characterised by predominant negative symptoms, oral doses between 50 mg/day and 300 mg/day are

recommended. Doses should be adjusted individually.

Amisulpride Mylan can be administered once daily orally at a dose up to 400 mg. Higher doses should be divided in

two doses.

Elderly

The safety of amisulpride has been examined in a limited number of elderly patients. Amisulpride Mylan should be

used with particular caution because of a possible risk of hypotension or sedation (see section 5.2). Reduction in dosage

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may also be required because of renal insufficiency.

Paediatric population

The efficacy and safety of amisulpride from puberty to the age of 18 years have not been established: There are limited

data available on the use of amisulpride in adolescents in schizophrenia. Therefore, the use of amisulpride from puberty

to the age of 18 years is not recommended; in children up to puberty amisulpride is contraindicated, as its safety has not

yet been established. (see section 4.3).

Patients with renal impairment

Amisulpride Mylan is eliminated by the renal route. In renal insufficiency, the dose should be reduced to half in patients

with creatinine clearance (CRCL) between 30-60 mL/min and to a third in patients with CRCL between 10-30 mL/min.

As there is no experience in patients with severe renal impairment (CRCL < 10 mL/min), particular care is

recommended in these patients (see sections 4.4 and 5.2).

Patients with hepatic impairment

Since amisulpride is weakly metabolised, a dosage reduction should not be necessary.

Method of administration:

Amisulpride Mylan tablets can be administered independently from the meals. Tablets should be taken whole or halved

with a sufficient amount of liquid.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Concomitant prolactin-dependent tumors (e.g. pituitary gland prolactinomas or breast cancer)

Phaeochromocytoma.

Children up to puberty.

Lactation.

In combination with levodopa (see section 4.5).

4.4 Special warnings and precautions for use

As with other neuroleptics, Neuroleptic Malignant Syndrome, a potentially fatal complication, characterised by

hyperthermia, increased muscle rigidity, autonomic instability, altered consciousness and elevated CPK, may occur. In

the event of hyperthermia, particularly with high daily doses, all antipsychotic medicines including Amisulpride Mylan

should be discontinued.

Amisulpride Mylan is eliminated by the renal route. In cases of renal insufficiency, the dose should be decreased and

intermittent treatment should be considered (see section 4.2).

Amisulpride Mylan can lower the seizure threshold. Therefore patients with a history of seizures should be closely

monitored during amisulpride therapy.

In elderly patients, amisulpride therapy, like other neuroleptics, should be used with particular caution because of a

possible risk of hypotension or sedation. Reduction in dosage may also be required in case of renal insufficiency.

As with other antidopaminergic agents, caution should be also exercised when prescribing Amisulpride Mylan to

patients with Parkinson's disease since it may cause worsening of the disease. Amisulpride Mylan should be used only if

neuroleptic treatment cannot be avoided.

Prolongation of QT interval

Amisulpride induces prolongation of the QT interval. This effect is known to potentiate the risk of serious ventricular

arrhythmias such as torsades de pointes.Caution should be exercised when amisulpride is prescribed in patients with

known cardiovascular disease or family history of QT prolongation, and concomitant use with neuroleptics should be

avoided.

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Particular caution is also advised in the following situations:

- significant bradycardia

- congenital prolongation of the QT interval.

- electrolyte imbalance, in particular, hypokalaemia, hypomagnesaemia,

- concomitant use of medicinal products that cause QT interval prolongation (see section 4.5).

Stroke

In randomised clinical trials versus placebo performed in a population of elderly patients with dementia and treated with

certain atypical antipsychotic medicines, a 3-fold increase of the risk of cerebrovascular events has been observed. The

mechanism of such risk increase is not known. An increase in the risk with other antipsychotic medicines, or other

populations of patients cannot be excluded. Amisulpride Mylan should be used with caution in patients with stroke risk

factors.

Venous Thromboembolism

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 Amisulpride Mylan and preventive measures undertaken.

Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics, including amisulpride.

Unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8), and requires immediate

haematological investigation.

Breast cancer

Amisulpride causes an increase in plasma prolactin levels. Therefore, caution should be exercised and patients with a

history or a family history of breast cancer should be closely monitored during amisulpride therapy. Amisulpride is

contraindicated in patients with breast cancer (see sections 4.3 and 4.8).

Elderly people with Dementia

Elderly patients with dementia-related psychosis treated with atypical antipsychotics had an increased risk of death

compared to placebo in a meta-analysis of 17 controlled trials of atypical antipsychotics.

The observed risk of death was 1.6 to 1.7 times the risk of death in placebo-treated patients. The rate of death in patient

treated with atypical antipsychotic was about 4.5%, compared to a rate of about 2.6% in the placebo group during a

typical 10-week controlled trial. There were different causes of death in clinical trials with atypical antipsychotics, but

most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g.,

pneumonia) in nature.

Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic

drugs may increase mortality.

The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic

drug as opposed to some characteristic(s) of the patients is not clear.

Amisulpride Mylan is not approved for the treatment of patients with dementia-related behavioural disturbances.

Other

Hyperglycemia has been reported in patients treated with some atypical antipsychotic agents, including amisulpride,

therefore patients with an established diagnosis of diabetes mellitus or with risk factors for diabetes, who are started on

Amisulpride Mylan, should get appropriate glycaemic monitoring.

The concomitant prescription of other antipsychotics should be avoided.

Withdrawal symptoms including nausea, vomiting and insomnia have been described after abrupt cessation of high

doses of antipsychotic drugs. Recurrence of psychotic symptoms may also occur, and the emergence of involuntary

movement disorders (such as akathisia, dystonia and dyskinesia) have been reported with amisulpride. Therefore,

gradual withdrawal of Amisulpride Mylan is advisable.

Benign pituitary tumour

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Amisulpride may increase prolactin levels. Cases of benign pituitary tumours such as prolactinoma have been observed

during amisulpride therapy. In case of very high levels of prolactin or clinical signs of pituitary tumour (such as visual

field defect and headache), pituitary imaging should be performed. If the diagnosis of pituitary tumour is confirmed, the

treatment with amisulpride must be stopped.

Lactose

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose

malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Contraindicated combinations:

Levodopa: reciprocal antagonism of effects between levodopa and neuroleptics. Amisulpride may oppose the effect of

dopamine agonists e.g. bromocriptine, ropirinole.

Combinations which are not recommended:

Amisulpride Mylan may enhance the effects of alcohol.

Combinations which must be taken into account:

depressants

including

narcotics,

anaesthetics,

analgesics,

sedative

-antihistamines,

barbiturates

benzodiazepines and other anxiolytic medicines, clonidine and derivatives.

Antihypertensive medicines and other hypotensive medications.

Caution is advised when prescribing amisulpride with medicines known to prolong the QT interval,

e.g.,

class IA

antiarrhythmics

(e.g.,

quinidine,

disopyramide)

and class

antiarrhythmics

(e.g.,

amiodarone,

sotalol),

some

antihistamines, some other antipsychotics and some antimalarials (e.g., mefloquine) (see section 4.4)

4.6 Fertility, pregnancy and lactation

Pregnancy

Amisulpride did not show reproductive toxicity in animals. Lower fertility associated with pharmacological effect of the

product (by means of prolactin) was found. No teratogenic effects of amisulpride were noted.

There is only very limited clinical data on administration of the medicinal product during pregnancy. Therefore the

safety of amisulpride during pregnancy in humans has not been established.

Use of the medicinal product during

pregnancy is not recommended unless the benefit outweighs the possible risk.

Neonates exposed to antipsychotics,

including amisulpride,

during the third trimester

pregnancy are at

risk of

adverse reactions

including extrapyramidal

and/or

withdrawal

symptoms

that

may vary in severity and duration

following delivery (see section 4.8). There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence,

respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breast-feeding

It is not known if amisulpride is excreted in breast milk. Breast-feeding is therefore contraindicated.

4.7 Effects on ability to drive and use machines

Amisulpride Mylan can cause somnolence and blurred vision and therefore also reduce the ability to drive vehicles and

operate machines, even when used at recommended doses (see section 4.8).

4.8 Undesirable effects

Adverse reactions have been ranked under the headings of frequency using the following convention:

Very common (

1/10); common (

1/100, <1/10); uncommon (

1/1000, <1/100); rare (

1/10000, <1/1000); very rare

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(<1/10000); frequency not known (cannot be determined from available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Clinical data

The following adverse effects have been observed in controlled clinical trials. It should be noted that in some instances

it could be difficult to differentiate adverse events from symptoms of the underlying disease.

Immune system disorders:

Uncommon: Allergic reactions

Endocrine disorders:

Common: Amisulpride causes an increase in plasma prolactin levels, which is reversible after drug

discontinuation. This may result in galactorrhoea, amenorrhoea or menstrual disorder, gynaecomastia, breast

pain and erectile dysfunction.

Metabolism and nutrition disorders:

Uncommon: Hyperglycemia (see section 4.4)

Psychiatric disorders:

Common: Insomnia, anxiety, agitation, orgasmic dysfunction

Nervous system disorders:

Very common: Extrapyramidal symptoms may occur: Tremor, rigidity, hypokinesia, hypersalivation, akathisia,

dyskinesia. These symptoms are generally mild at optimal dosages and partially reversible without

discontinuation of amisulpride upon administration of antiparkinsonian medication. The incidence of

extrapyramidal symptoms, which is dose related, remains very low in treatment of patients with predominantly

negative symptoms with doses of 50-300 mg/day.

Common:

- Acute dystonia (spasmodic torticollis, oculogyric crisis, trismus) may appear. This is reversible without

discontinuation of amisulpride upon administration of antiparkinsonian medication.

- Somnolence

Uncommon:

- Tardive dyskinesia characterised by rhythmic, involuntary movements primarily of the tongue and/or face

has been reported, usually after long-term administration. Antiparkinsonian medication is ineffective or may

induce aggravation of the symptoms.

- Seizures

Cardiac disorders:

Common: Hypotension

Uncommon: Bradycardia

Gastrointestinal disorders:

Common: Constipation, nausea, vomiting, dry mouth

Investigations:

Common: Weight gain

Uncommon: Elevations of hepatic enzymes, mainly transaminases

Postmarketing surveillance:

The following undesirable effects were also reported (spontaneous reports):

Endocrine disorders

Not known: Benign pituitary tumour such as prolactinoma (see section 4.3 and section 4.4).

Blood and Lymphatic system disorders:

Not known: Leukopenia, neutropenia and agranulocytosis (see section 4.4)

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Metabolism and nutrition disorders:

Not known: Hypertriglyceridaemia and hypercholesterolaemia. Hyponatraemia, syndrome of inappropriate antidiuretic

hormone secretion (SIADH).

Psychiatric disorders:

Not known: Confusion

Nervous system disorders:

Not known: Neuroleptic malignant syndrome symptom (see section 4.4), which is a potentially fatal

complication.

Eye disorders:

Not known: Blurred vision

Cardiac disorders:

Not known: prolongation of the QT interval and ventricular arrhythmia such as torsades de pointes, ventricular

tachycardia, which could lead to ventricular fibrillation or cardiac arrest, sudden death (see section 4.4).

Vascular disorders:

Not known: Cases of venous thromboembolism, including cases of pulmonary embolism, sometimes fatal and cases of

deep vein thrombosis have been reported with antipsychotic drugs (see section 4.4)

Skin and subcutaneous tissue disorders:

Not known: Angioedema, urticaria

Musculoskeletal and connective tissue disorders:

Not known: Osteopenia, osteoporosis

Pregnancy, puerperium and perinatal conditions

Not known:

Drug withdrawal syndrome neonatal (see section 4.6)

Respiratory, thoracic and mediastinal disorders

Not known: Nasal congestion

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any

suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:medsafety@hpra.ie.

4.9 Overdose

Experience with overdose is limited. Exaggeration of pharmacological effects of the drug has been reported with

symptoms such as drowsiness and sedation, coma, hypotension and extrapyramidal symptoms. Fatal outcomes have

been reported mainly in combination with other psychotropic agents.

In cases of acute overdose, the possibility of multiple drug intakes should be considered.

Since amisulpride is weakly dialysed, hemodialysis is of no use to eliminate the drug.

There is no specific antidote to amisulpride. Appropriate supportive measures should therefore be instituted with close

supervision of vital functions including continuous cardiac monitoring due to the risk of prolongation of the QT

interval, until complete recovery of the patient.

If severe extrapyramidal symptoms occur, anticholinergic agents should be administered.

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5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Psycholeptics, Antipsychotics, Benzamides

ATC code: N05AL05

Amisulpride binds selectively with a high affinity to human dopaminergic D

receptor subtypes whereas it is devoid

of affinity for D

and D

receptor subtypes.

Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonin, alpha-adrenergic, H

-histamine and

cholinergic receptors. In addition, amisulpride does not bind to sigma receptors.

In animal studies, at high doses, amisulpride blocks dopamine receptors located in the limbic system in preference to

those in the striatum. As opposed to classical neuroleptics, it does not cause catalepsy and hypersensitivity to D

dopamine receptors does not develop after repeated treatment. At low doses it preferentially blocks pre-synaptic D

receptors, and causes the secretion of dopamine which is responsible for its disinhibitory effects.

This atypical pharmacological profile can explain amisulpride’s antipsychotic effect at higher doses through post-

synaptic dopamine receptor blockade and its effect on negative symptoms at lower doses caused by the inhibition of

pre-synaptic dopamine receptors. Decreased incidence of undesirable extrapyramidal symptoms can be caused by the

preferential activity in the limbic system.

In clinical

studies,

which monitored patients

with acute exacerbation of

schizophrenia,

amisulpride significantly

reduced secondary negative symptoms as well as affective symptoms and psychomotor slow-down.

5.2 Pharmacokinetic properties

Absorption

In man, amisulpride shows two absorption peaks: one which is attained rapidly, one hour post-dose and a second

between 3 and 4 hours after administration. Corresponding plasma concentrations are 39 ± 3 and 54 ± 4 ng/ml after a 50

mg dose.

Distribution

The volume of distribution is 5.8 l/kg, plasma protein binding is low (16%) and no drug interactions are known.

Absolute bioavailability is 48%.

Biotransformation

Amisulpride is weakly metabolised: two inactive metabolites, accounting for approximately 4% of the dose, have been

identified. There is no accumulation of amisulpride and its pharmacokinetics remains unchanged after the

administration of repeated doses.

Elimination

The elimination half-life of amisulpride is approximately 12 hours after an oral dose. Amisulpride is eliminated

unchanged in the urine. 50% of an intravenous dose is excreted via the urine, of which 90% is eliminated in the first 24

hours. Renal clearance is in the order of 20 l/h or 330 ml/min. A carbohydrate rich meal (containing 68% fluids)

significantly decreases the AUCs, Tmax and Cmax of amisulpride but no changes were seen after a high fat meal.

However, the significance of these findings in routine clinical use is not known.

Hepatic impairment: since the drug is weakly metabolised, the dosage needs not to be reduced in patients with hepatic

insufficiency.

Renal impairment: The elimination half-life is unchanged in patients with renal insufficiency while systemic clearance

is reduced by a factor of 2.5 to 3. The AUC of amisulpride in mild renal failure increased two fold and almost tenfold in

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moderate renal failure (see section 4.2). Experience is however limited and there is no data with doses greater than 50

Amisulpride is very weakly dialysed.

Limited pharmacokinetic data in elderly subjects (> 65 years) show that a 10-30 % rise occurs in C

and AUC

after a single oral dose of 50 mg. No data are available after repeat dosing.

5.3 Preclinical safety data

An overall review of the completed safety studies indicates that amisulpride is devoid of any general,

organ-specific,

teratogenic, mutagenic or carcinogenic risk. Changes observed in rats and dogs at doses below the maximum tolerated

dose are either

pharmacological

effects or

are devoid of

major

toxicological

significance under

these conditions.

Compared with the maximum recommended dosages in man, maximum tolerated doses are 2 and 7 times greater in the

rat (200 mg/kg/d) and dog (120 mg/kg/d), which corresponds to 1.5 – 4.5 higher AUC in rat than in human.

A mouse carcinogenicity study (120 mg/kg/d) and reproductive studies (160, 300 and 500 mg/kg/d respectively in rat,

rabbit

and mouse) were performed.

The exposure of the animals to amisulpride during these latter studies was not

evaluated.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose monohydrate

Methylcellulose

Sodium starch glycolate (type A)

Cellulose, microcrystalline

Magnesium stearate

6.2 Incompatibilities

Not applicable

6.3 Shelf life

36 months

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

PVC/Aluminium blister of 10, 30, 60, 90, 120 or 150 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

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McDermott Laboratories Ltd t/a Gerard Laboratories

35/36 Baldoyle Industrial Estate

Grange Road

Dublin 13

Ireland

8 MARKETING AUTHORISATION NUMBER

PA0577/125/003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 28

August 2009

Date of last renewal: 16

September 2013

10 DATE OF REVISION OF THE TEXT

February 2017

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