Treatment of schizophrenia.

Generally speaking

· If the daily dose is ≤ 400 mg, the administration will be in a
· Over 400 mg, the administration will be done in 2 doses per day.

Acute psychotic episodes

It is possible to start with the IM route for a few days at a maximum dose of 400 mg / day and then relay by the oral route.
The recommended oral dose is 400 to 800 mg / day, the maximum dosage should not exceed 1200 mg / day. The tolerance of doses above 1200 mg / day has not been widely evaluated. Therefore, these doses should not be used.

The dosage will then be maintained or adjusted according to the patient's individual response.
In all cases, the maintenance treatment will be established individually with the minimum effective dose.

Episodes: negative predominant

The recommended dosage is 50 to 300 mg / day. Dosages will be adjusted individually. The optimal dosage is around 100 mg per day.
Child and adolescent

The efficacy and tolerability of amisulpride of puberty at age 18 years have not been established: the available data on the use of amisulpride in schizophrenia in adolescents are limited Therefore, the use of amisulpride is not recommended from puberty until the age of 18 years. In children less than 15 years of age, amisulpride is contraindicated (see section Contraindications).
Person, aged

Friendulpride should be used with particular caution in this population because of the risk of hypotension and sedation (see Warnings and Precautions for Use).
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Renal insufficiency

Due to the renal elimination of amisulpride, patients with creatinine clearance (ICRC) in the range of 30 to 60 ml / min and To one-third in patients with creatinine clearance between 10 and 30 ml / min.
In the absence of data in patients with severe renal impairment (ICRC

Hepatic Insufficiency

Since amisulpride is weakly metabolized, dosage reduction is not necessary in patients with hepatic impairment

Tablet, white elongate scored film engraved on an 'AMI' and '400' side on either side of the fractionating bar.

Pharmacotherapeutic group, ANTIPSYCHOTICS, ATC code: N05AL05.

The amisulpride is an antipsychotic of the class of substituted benzamides.

Its pharmacodynamic profile is characterized by selective and predominant affinity to the D2 and D3 dopaminergic receptors of the limbic system. Friendsulpride has no affinity for serotonergic receptors and for other histamine, cholinergic, and adrenergic neuroreceptors.
In large doses in studies carried out in animals, amisulpride blocks preferentially the dopaminergic neurons of the meso-limbic system compared with those of the striatal system. This specific affinity may explain the predominant antipsychotic effects of amisulpride compared to its extrapyramidal effects

In low doses, amisulpride blocks preferentially receptors, presynaptic dopaminergic D2 / D3, which could explain its action on negative symptoms.


Attention is drawn in particular to the risk of drowsiness associated with the use of this medicinal product in vehicle operators and users of machinery.
This medicinal product MUST NOT BE USED in the following cases

· Known hypersensitivity to amisulpride or to any other constituent of the product

Severe hypertensive accidents have been reported in pheochromocytoma carriers with antidopaminergic drugs including some benzamides, so it is prudent to refrain from prescribing this product in known or suspected carriers of pheochromocytoma

· Children under 15 years of age, in the absence of clinical data

· Breastfeeding

· Prolactin-dependent tumor known or suspected by, eg pituitary adenoma with prolactin and breast cancer

· In association with levodopa (see section Interactions with other medicinal products and other forms of interactions)

Neuroleptic malignant syndrome

As with other neuroleptics, the occurrence of neuroleptic malignant syndrome (hyperthermia, muscle stiffness, neurovegetative disorders, altered consciousness, increased CPK) is possible. In case of hyperthermia, especially with high daily doses, any antipsychotic treatment, including amisulpride, should be discontinued.


The amisulpride prolongs in a dose-dependent manner the QT interval. This effect, known to potentiate the risk of occurrence of severe ventricular arrhythmias, in particular of torsades de pointes, is increased by the presence of bradycardia, hypokalaemia, congenital long QT Or acquired (combination with an interval-increasing drug QTc) (see section Effects, undesirable)

It is therefore appropriate, when the clinical situation permits, to ensure before any administration of the absence of factors which may favor the occurrence of this disorder of the rhythm

· Bradycardia less than 55 beats per minute

· Hypokalemia

· Congenital prolongation of the QT interval

· Ongoing treatment with a medication likely to result in marked bradycardia (

Although the causes of death in clinical trials with atypical antipsychotics were varied, most of these deaths appeared to be either of cardiovascular origin (eg heart failure, sudden death) or infectious ( For example pneumonia).

Epidemiological studies suggest that, as with atypical antipsychotics, treatment with classical antipsychotics may increase mortality.



Cases of venous thromboembolism (VTE) have been reported with antipsychotics.) Since patients treated with antipsychotics often have risk factors for VTE, all risk factors for VTE should be Identified before and during treatment with AMISULPRIDE ZENTIVA and preventive measures should be taken where appropriate (see section Effects, undesirable).


Cases of hyperglycemia or glucose intolerance and of the onset or exacerbation of diabetes have been reported in patients treated with certain atypical antipsychotics including amisulpride (see section 4.4) .

Patients treated with AMISULPRIDE ZENTIVA should be monitored clinically and biologically according to current recommendations. Special attention should be paid to patients with diabetes or who have diabetes risk factors

Convulsion

The amisulpride may decrease the threshold, epileptogenic. Patients with a history of convulsive seizures should therefore be closely monitored during treatment by AMISULPRIDE ZENTIVA.


Due to the renal elimination of the product, it is recommended to reduce the dosage in renal insufficiency or other treatment may be considered (see section 4.2). There is no data in patients with severe renal impairment (see section Posology and method of administration).
Like all antipsychotics, amisulpride should be used with caution, especially in elderly patients, because of a potential risk of sedation and hypotension. >
Like any other antidopaminergic drug, amisulpride should be used with caution, in Parkinson's, because of a risk of deterioration of the disease. Friendulpride should only be used if neuroleptic treatment is essential.

Weaning syndrome

Symptoms of withdrawal have been described after abrupt discontinuation of high doses of antipsychotics. The occurrence of involuntary movements (such as akathisia, dystonia and dyskinesia) have been reported with amisulpride. Therefore, a progressive stop of the amisulpride is advised.

Other

This medication is not recommended in combination with alcohol, antiparkinsonian dopaminergic agents, antiparasitic drugs, tetrahedrons, methadone, other neuroleptics and medicines, which can lead to torsades de pointes ( See section Interaction with other medicinal products and other forms of interaction)

Related to excipients

This medicine contains lactose and is not recommended for use in patients with galactose intolerance, Lapp lactase deficiency or malabsorption syndrome, glucose or galactose (hereditary or rare diseases). Br>

+; Sedative drugs

It must be taken into account that many drugs or substances can add up to their depressant effects of the central nervous system and contribute to diminish vigilance. These include morphine derivatives (analgesics, antitussives and substitution treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics, other than benzodiazepines (eg, meprobamate), hypnotics, antidepressants, sedatives (Amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), antihistamines H1, sedatives, central antihypertensives, baclofen and thalidomide
+ Drugs capable of giving torsades of points

This severe heart rhythm disorder can be caused by a number of drugs, whether antiarrhythmic or not. Hypokalemia (see hypokalaemic drugs) is a factor in promoting bradycardia (see bradycardia drugs) or prolongation of the QT interval, congenital or acquired. >

The medicinal products concerned are class Ia and III antiarrhythmics, some of them neuroleptics.

For erythromycin, spiramycin and vincamine, only the forms administered intravenously are concerned by this interaction.

The use of a drug, twisting with another medication, is contraindicated in general.

However, methadone, as well as certain subclasses, are the exception, this rule

· Antiparasitics (halofantrine, lumefantrine, pentamidine) are only advised against with other torsadogens

· Neuroleptics capable of giving torsades de pointes are also not advised and not contraindicated with other torsadogens.
Associations contraindicated

(See section Contraindications.)

+; Levodopa

Reciprocal antagonism of the dopaminergic agonist and neuroleptics.

Associations, deprecated

(See Warnings and Precautions for Use)

+; Antiparasitics capable of giving torsades de pointes (halofantrine, lumefantrine, pentamidine)

Increased risk of ventricular rhythm disorders, in particular of torsades de pointes.

If it is possible, stop the antifungal azole.
If the association can not be avoided, pre-QT checking and ECG monitoring.

Antiparkinsonian dopaminergic agents (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline)
Reciprocal antagonism of dopaminergic and neuroleptics.

Dopaminergic can cause or aggravate psychotic disorders. In the case of neuroleptic treatment in dopaminergic patients treated with dopaminergic patients, the latter should be gradually decreased until they stop (their sudden arrest exposes them to a risk of malignant neuroleptic syndrome ").

Other medicinal products capable of giving tarts of class Ia (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, ibutilide) and other drugs such as bepridil, cisapride, diphenemil; Erythromycin IV, mizolastine, vincamine IV, moxifloxacin, spiramycin IV

Increased risk of rhythm disorders, including ventricular torsades de pointes

+ Other neuroleptics capable of giving torsades of points (chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipampone, pipotiazine, sertindole, sulpiride, sultopride, tiapride, veralipride, zuclopentixol) >

Increased risk of rhythm disorders, including ventricular torsades de pointes

+ Alcohol consumption

Supplementation with alcohol, the sedative effect of neuroleptics.

The alteration of vigilance can make driving dangerous and the use of machinery.

Avoid drinking alcoholic beverages and medicines containing alcohol

+; Methadone

Increased risk of ventricular rhythm disorders, in particular of torsades de pointes.

Associations subject to precautions for use

+, Beta-blockers in heart failure (bisoprolol, carvedilol, metoprolol, nebivolol)

Increased risk of ventricular rhythm disorders, particularly torsades de pointes. Surveillance, Clinical and ECG.

(Including class Ia antiarrhythmics, beta-blockers, certain class III antiarrhythmics, certain calcium antagonists, digitalis, pilocarpine, anticholinesterasics)
Increased risk of ventricular rhythm disorders, in particular of torsades de pointes.

Clinical Surveillance and ECG.

Hypokalemic agents (hypokalemic diuretics, alone or together, laxative stimulants, glucocorticoids, tetracosactide and amphotericin B IV)

Increased risk of ventricular rhythm disorders, in particular of torsades de pointes.

Correct any hypokalaemia before, administer the product and perform clinical, electrolytic and ECG monitoring.

Associations to be taken into account

+ Antihypertensive drugs

Increased risk of hypotension, especially orthostatic.

Beta-blockers (except esmolol, sotalol and beta-blockers, used in heart failure)

Vasodilator effect and risk of hypotension, in particular orthostatic (additive effect).
+; Nitrated and related derivatives

Increased risk of hypotension, especially orthostatic.

Not applicable.

To date, data concerning acute overdosage with amisulpride are limited. The signs and symptoms that have been reported resulted generally from an increase in the pharmacological effects of the drug, translated into the clinical plane by: somnolence, sedation, coma, hypotension and extrapyramidal symptoms. Fatal outcomes have been reported mainly during association with other antipsychotics.


· Close monitoring of vital functions.

Monitoring cardiac monitoring (risk of prolongation of Q.T. interval) which will be continued until the patient is recovered

· In the event of severe extrapyramidal symptoms, anticholinergic therapy should be administered.

· Since amisulpride is weakly dialyzable, hemodialysis has limited interest in eliminating the product.

Pregnancy

In the animal, amisulpride has not shown reproductive toxicity. A decrease in fertility due to pharmacological effects of the drug (prolactin-dependent effect) was observed. It has not been shown to have an effect: the teratogen of amisulpride.

In clinical settings, data available during pregnancy are limited. Consequently, the safety of use of amisulpride during pregnancy has not been established. The use of amisulpride during pregnancy is not recommended unless the expected benefits justify the potential risks.

If amisulpride is used, during pregnancy the adverse effects of amisulpride may be observed in newborns. As a result, newborns should be carefully monitored.


In the absence of data on passage through breast milk, breast-feeding is contraindicated.

The undesirable effects were ranked in order of frequency using the following convention, very common ≥1 / 10, frequent, ≥1 / 100,

Skin and tissue disorders, subcutaneous

Frequency, undetermined

Angioedema, urticaria.

Treatment of schizophrenia.