Amisulpride 200mg Tablets are indicated for the treatment of acute and chronic schizophrenic
disorders, in whichpositive symptoms (such as delusions, hallucinations, and thought disorders)
and/or negative symptoms (such as bluntedaffect, emotional and social withdrawal) are
prominent, including patients characterised by predominant negativesymptoms.

For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended. In
individual cases, thedaily dose may be increased up to 1200 mg/d. Doses above 1200 mg/d have
not been extensively evaluated for safetyand therefore should not be used. No specific titration
is required when initiating the treatment with amisulpride. Dosesshould be adjusted according
to individual response.
For patients with mixed positive and negative symptoms, doses should be adjusted to obtain
optimal control of positivesymptoms.
Maintenance treatment should be established individually with the minimally effective dose.
For patients characterised by predominant negative symptoms, oral doses between 50 mg/d and
300 mg/d arerecommended. Doses should be adjusted individually.
Amisulpride can be administered once daily at oral doses up to 300 mg, higher doses should be
administered bid.
The minimum effective dose should be used.
Elderly:
The safety of Amisulpride has been examined in a limited number of elderly patients.
Amisulpride should be used withparticular caution because of a possible risk of hypotension or
sedation. Reduction in dosage may also be requiredbecause of renal insufficiency.
Children:
The efficacy and safety of amisulpiride from puberty to the age of 18 years have not been
established. There are limiteddata available on the use of amisulpiride in adolescents in
schizophrenia. Therefore, the use of amisulpiride from pubertyto the age of 18 years is not
recommended; in children up to puberty amisulpride is contraindicated, as its safety has notyet
been established (see section 4.3).

Renal insufficiency:
Amisulpride 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 (CR CL < 10 ml/min)
particular care is recommended in these patients (see section 4.4).
Hepatic insufficiency:
Since the drug is weakly metabolised a dosage reduction should not be necessary.

• Hypersensitivity to the active substance or to any of the excipients listen in section 6.1 • Concomitant prolactin-dependent tumours e.g. pituitary gland prolactinomas or breast cancer (see section 4.4 and 4.8) • Phaeochromocytoma • Children before the onset of puberty • lactation • Combination with levodopa (see Section 4.5) • Combination with the following medication which could include torsades de pointes: - Class Ia antiarrhythmic agents such as quinidine, disopyramide, procainamide - Class III antiarrhythmic agents such as amiodarone, sotalol – Other medicines such as bepidril, cisapride, sultopride, thioridazine, IV erythromycin, IV vincamine, halofantrine, pentamidine, sparfloxacin.

As with other neuroleptics, Neuroleptic Malignant Syndrome, a potentially fatal complication,
characterized by hyperthermia, muscle rigidity, autonomic instability, altered consciousness
and elevated CPK, may occur. In the event of hyperthermia, particularly with high daily doses,
all antipsychotic drugs including Amisulpride should be discontinued.
Hyperglycaemia 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, should get appropriate glycaemic
monitoring.
Amisulpride is eliminated by the renal route. In cases of severe renal insufficiency, the dose
should be decreased and intermittent treatment should be considered (see Section 4.2).
Amisulpride may lower the seizure threshold. Therefore patients with a history of epilepsy
should be closely monitored during Amisulpride therapy.
In elderly patients, Amisulpride, 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
because of renal insufficiency.
As with other antidopaminergic agents, caution should be also exercised when prescribing
Amisulpride to patients with Parkinson's disease since it may cause worsening of the disease.
Amisulpride should be used only if neuroleptic treatment cannot be avoided.
Acute withdrawal symptoms including nausea, vomiting and insomnia have very rarely 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
akathisa, dystonia and dyskinesia) has been reported. Therefore, gradual withdrawal is
advisable.

Prolongation of the QT interval
Caution should be exercised when amisulpride is prescribed in patients with known
cardiovascular disease or familyhistory of QT prolongation.
Concomitant antipsychotics should be avoided.
Stroke:
In randomized clinical trials versus placebo performed in a population of elderly patients with
dementia and treated with certain atypical antipsychotic drugs, 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 drugs, or other populations of patients cannot
be excluded. Amisulpride should be used with caution in patients with stroke risk factors.

Increased Mortality in Elderly people with Dementia:
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an
increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10
weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drugtreated
patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over
the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was
about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of
death in clinical trials with atypical antipsychotics were varied, 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 is not licensed for the treatment of dementia-related behavioural disturbances.

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 and
preventive measures undertaken
Breast cancer:
Amisulpride may increase 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.
Benign pituitary tumour:
Amisulpride may increase prolactin levels. Cases of benign pituitary tumours such as
prolactinoma have been observed during Amisulpride therapy (see section 4.8). 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 (see section 4.3)
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.

Patients with rare hereditary problems of galactose intolerance, the total lactase deficiency or
glucose-galactose malabsorption should not take this medicine.
Severe liver toxicity has been reported with amisulpride use. Patients should be instructed to
report immediately signs such as asthenia, anorexia, nausea, vomiting, abdominal pain or
icterus to a physician. Investigations including clinical examination and biological assessment
of liver function should be undertaken immediately (see section 4.8).

COMBINATIONS WHICH ARE CONTRAINDICATED
Levodopa: reciprocal antagonism of effects between levodopa and neuroleptics. Amisulpride
may oppose the effect of dopamine agonists e.g. bromocriptine, ropinirole
COMBINATIONS WHICH ARE NOT RECOMMENDED
Amisulpride may enhance the central effects of alcohol
COMBINATIONS WHICH REQUIRE PRECAUTIONS FOR USE
Medications which enhance the risk of torsades de pointes:
- Bradycardia-inducing medications such as beta-blockers, bradycardia-inducing calcium
channel blockers such as diltiazem and verapamil, clonidine, guanfacine; digitalis
- Medications which induce hypokalaemia: hypokalaemic diuretics, stimulant laxatives, IV
amphotericin B, glucocortocoids, tetracosactides
- Neuroleptics such as pimozide, haloperidon; imipramine, antidepressants; lithium
COMBINATIONS TO BE TAKEN INTO ACCOUNT
• CNS depressants including narcotics, anaesthetics, analgesics, sedative H1 antihistamines,
barbiturates, benzodiazepines and other anxiolytic drugs, clonidine and derivatives
• Antihypertensive drugs and other hypotensive medications
• Co-administration of amisulpride and clozapine may lead to an increase in plasma levels of
amisulpride
• Caution is advised when prescribing amisulpride with medicines known to prolong the QT
interval, e.g., class I Aantiarrythmics (e.g., quinidine, disopyramide) and class III
antiarrythmics (e.g. amiodarone, Sotalol), some antihistaminics, some other antipsychotics and
antimalarials (e.g., mefloquine) (see section 4.4)

Pregnancy
There are only limited data available from the use of amisulpride in pregnant women. The safety
of amisulpride during human pregnancy has not been established. Amisulpride crosses the
placenta. Studies in animals have shown reproductive toxicity (see section 5.3). The use of
amisulpride is not recommended during pregnancy and in women of childbearing potential not
using effective contraception, unless the benefits justify the potential risks.
Neonates exposed to antipsychotics including Amisulpride tablets during the third trimester of
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
Amisulpride is excreted into breastmilk in rather large amounts above the accepted value of
10% of the maternal weight-adjusted dosage in some cases, but blood concentrations in
breastfed infants have not been evaluated. There is insufficient information on the effects of
amisulpride in newborns/infants. A decision must be made whether to discontinue breastfeeding
or to abstain from amisulpride therapy taking into account the benefit of breastfeeding
for the child and the benefit of therapy for the woman.
Fertility
A decrease in fertility linked to the pharmacological effects of the drug (prolactin-mediated
effect) was observed in treated animals.

Even used as recommended, amisulpride may cause somnolence and blurred vision so that the
ability to drive vehicles or operate machinery can be impaired (see Section 4.8).

Adverse effects have been ranked under headings of frequency using the following convention:
Very common 􀀋􀂕 1/10); common 􀀋􀂕 1/100; <1/10); uncommon 􀀋􀂕 1/1,000; <1/100); rare 􀀋􀂕
1/10,000; <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available
data).
Clinical trials data
The following adverse effects have been observed in controlled clinical trials. It should be noted
that in some instances it can be difficult to differentiate adverse events from symptoms of the
underlying disease.
Nervous system disorders
Very common: Extrapyramidal symptoms may occur: tremor, rigidity, hypokinesia,
hypersalivation, akathisia, dyskinesia. Thesesymptoms are generally mild at optimal dosages
and partially reversible without discontinuation of amisulpride uponadministration of
antiparkinsonian medication. The incidence of extrapyramidal symptoms which is dose related,
remainsvery low in the treatment of patients with predominantly negative symptoms with doses
of 50-300mg/day.
Common: Somnolence, acute dystonia (spasm torticolis, oculogyric crisis, trismus) may appear.
This is reversible withoutdiscontinuation of amisulpride upon treatment with an
antiparkinsonian agent.
Uncommon: Seizures, tardive dyskinesia characterised by rhythmic, involuntary movements
primarily of the tongue and/or face havebeen reported, usually after long term administration.
Antiparkinsonian medication is ineffective or may induce aggravation of the symptoms.
Rare: Neuroleptic Malignant Syndrome (see section 4.4), which is a potentially fatal
complication
Not known: Restless legs syndrome

Eye disorders
Common: blurred vision (see section 4.7)
Psychiatric disorders
Common: Insomnia, anxiety, agitation, orgasmic dysfunction
Uncommon: Confusion
Gastrointestinal disorders
Common: Constipation, nausea, vomiting, dry mouth.
Endocrine disorders
Common: Amisulpride causes an increase in plasma prolactin levels which is reversible after
drug discontinuation. Thismay result in galactorrhoea, amenorrhoea, gynaecomastia, breast
pain, and erectile dysfunction.
Rare: benign pituitary tumour such as prolactinoma (see section 4.3 and 4.4).
Metabolism and nutrition disorders
Uncommon: Hyperglycemia (see section 4.4), hypertriglyceridemia and hypercholesterolaemia
Rare: hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Investigations
Common: Weight gain
Uncommon: Elevation of hepatic enzymes, mainly transaminases
Immune system disorders
Uncommon: Allergic reaction
Blood and Lymphatic system disorders
Uncommon: Leukopenia, neutropenia (see section 4.4)
Rare: agranulocytosis (see section 4.4)
Cardiac disorders
Uncommon: bradycardia

Rare: QT interval prolongation, ventricular arrhythmias such as torsade de pointes, ventricular
tachycardia, ventricular fibrillation, cardiac arrest, sudden death (see section 4.4).
Vascular disorders
Common: Hypotension
Uncommon: Increase in blood pressure
Rare: Venous thromboembolism, including pulmonary embolism sometimes fatal, and deep
vein thrombosis (see section4.4)
Respiratory, thoracic and mediastinal disorders:
Uncommon: nasal congestion, pneumonia aspiration (mainly in association with other
antipsychotics and CNS depressants).
Skin and subcutaneous tissue disorders
Rare: Angioedema, urticaria
Not known: photosensitivity reaction
Musculoskeletal and connective tissue disorders:
Uncommon: osteopenia, osteoporosis
Renal and urinary disorders:
Uncommon: urinary retention
Pregnancy, puerperium and perinatal conditions
Not known: Drug withdrawal syndrome neonatal (see section 4.6).
To report any side effect(s):
􀁸 Saudi Arabia:
􀁸 The National Pharmacovigilance Center (NPC)
􀀐 SFDA Call Center: 19999
􀀐 E-mail: npc.drug@sfda.gov.sa
􀀐 Website: https://ade.sfda.gov.sa/

Experience with amisulpride in over dosage is limited. Exaggeration of the known
pharmacological effects of the drug have been reported. These include drowsiness and sedation,
coma, hypotension and extrapyramidal symptoms.
Fatal outcomes have been reported mainly in combination with other psychotropic agents.
In cases of acute over dosage, the possibility of multiple drug intake should be considered.
Since amisulpride is weakly dialysed, hemodialysis should not be used 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 risk of prolongation of the QT interval until the patient recovers.
If severe extrapyramidal symptoms occur, anticholinergic agents should be administered.

Pharmacotherapeutic group: Antipsychotics
ATC Code: NO5A LO5
Mechanism of action
Amisulpride binds selectively with a high affinity to human dopaminergic D2/D3 receptor
subtypes whereas it is devoid of affinity for D1, D4 and D5 receptor subtypes.
Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonic, 􀄮-
adrenergic, histamine H1 andcholinergic receptors. In addition, amisulpride does not bind to
sigma sites.
Pharmacodynamic effects
In animal studies, at high doses, amisulpride blocks dopamine receptors located in the limbic
structure in preference to those in the striatum.
At low doses it preferentially blocks pre-synaptic D2/D3 receptors, producing dopamine release
responsible for its disinhibitory effects.
This pharmacological profile explains the clinical efficacy of amisulpride against both negative
and positive symptoms of schizopheria.

Pharmacotherapeutic group: Antipsychotics
ATC Code: NO5A LO5
Mechanism of action
Amisulpride binds selectively with a high affinity to human dopaminergic D2/D3 receptor
subtypes whereas it is devoid of affinity for D1, D4 and D5 receptor subtypes.
Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonic, 􀄮-
adrenergic, histamine H1 andcholinergic receptors. In addition, amisulpride does not bind to
sigma sites.
Pharmacodynamic effects
In animal studies, at high doses, amisulpride blocks dopamine receptors located in the limbic
structure in preference to those in the striatum.
At low doses it preferentially blocks pre-synaptic D2/D3 receptors, producing dopamine release
responsible for its disinhibitory effects.
This pharmacological profile explains the clinical efficacy of amisulpride against both negative
and positive symptoms of schizopheria.

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) respectively in terms of AUC. No carcinogenic
risk, relevant to man, was identified in the rat at up to 1.5 to 4.5 times the expected human
AUC.
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.
In animal trials, amisulpride elicited an effect on foetal growth and development at doses
corresponding to Human Equivalent Dose of 2000 mg/day and upwards for a 50-kg patient.
There was no evidence for a teratogenic potential of amisulpride. Studies on the impact of
amisulpride on the behavior of the offspring have not been conducted.

For 100 mg & 200 mg:
Lactose monohydrate
Methyl cellulose
Cellulose, microcrystalline
Croscarmellose sodium
Magnesium stearate
For 400 mg:
Tablet core:
Lactose monohydrate
Methyl cellulose
Cellulose, microcrystalline
Croscarmellose sodium
Magnesium stearate
Tablet coating:
Basic butylated methacrylate copolymer
Titanium dioxide (E171)
Talc
Macrogol 6000
Magnesium stearate

Not applicable.

24 Months

Store below 30C.

Amisulpride tablets are available in Clear PVC/PVDC - Aluminium foil blister pack.
30's pack (10's Blister x 3).

No special requirements.