Expiration date: 01/2025

Description pharmaceutical form:

Tablets 100 mg: round flat, white or nearly white with Valium on one party and chasing «AMI 100" - on the other.

Tablets 200 mg: round flat, white or nearly white with Valium on one party and chasing «AMI 200" - on the other ..

Tablets 400 mg: oblong biconvex, film-coated white, engraved with "the AMI 400" and the fault line between "the AMI" and "400" - on one side.

Pharmacokinetics:

Amisulpride have observed two absorption peaks: one is reached rapidly, within an hour, and the second - between 3 and 4 hours after dosing. After ingestion of 50 mg Cmax, peaks corresponding to these, are (39 ± 3) and (54 ± 4) ng / mL.

The volume of distribution of 5.8 l / kg. Due to the low bond to plasma proteins (16%), are not expected to interact with other medications amisulpride level communication with the protein. The absolute bioavailability is 48%.

Amisulpride significantly metabolized by the liver (about 4%), identified by two inactive metabolite. In exchange taking amisulpride accumulation does not occur, and the pharmacokinetics does not change. When administered T1 / 2 of amisulpride is approximately 12 hours.

Amisulpride is excreted in the urine in unchanged form.

Kidney Cl is about 330 ml / min.

Carbohydrate-rich meal significantly reduces the AUC, Tmax and Cmax of amisulpride, while foods rich in fat changes the above pharmacokinetic parameters does not matter. However, the significance of these observations in everyday clinical practice is unknown.

Renal insufficiency. T1 / 2 is not changed in patients with renal insufficiency, but the systemic clearance is reduced by a factor of 2.5 to 3. AUC of amisulpride in mild degrees of kidney failure increases by half, and in renal failure of moderate severity - almost tenfold (see "How to use. and dose "). Experience with the drug in renal failure is limited, and there is no data in the reception amisulpride dose greater than 50 mg.

Amisulpride virtually displayed by hemodialysis.

Liver failure. Due to the fact that amisulpride significantly metabolized in the liver in hepatic failure accumulation of the drug and is not expected to reduce its dose is not required.

Elderly patients. When comparing the pharmacokinetic parameters of patients over 65 years with those of younger patients found that they have after a single oral administration of amisulpride 50 mg values ??Cmax, T1 / 2 and AUC by 10-30% higher. Data on the pharmacokinetic parameters in the elderly amisulpride at course intake no.

Description of the pharmacological actions:

Amisulpride is an antipsychotic drug from the group of substituted benzamides. The pharmacodynamic profile of amisulpride is caused by selective and predominant affinity for subtypes D2- and D3-dopaminergic receptors of the limbic system. Amisulpride has no affinity for serotonin and other neuroreceptors such as histamine, cholinergic and adrenergic receptors.

Animal studies have shown that when used in high doses, amisulpride more blocks dopaminergic neurons of the mesolimbic system than a similar system neurons in striatum. This is explained by the specific affinity, presumably, antipsychotic effects amisulpride predominance over its extrapyramidal effects.

When used in low doses, amisulpride blocks predominantly presynaptic dopaminergic D2- receptors and D3- than can be explained by its positive effect on negative symptoms.

Dosage:

INSTRUCTION for medical use Solian drug divisible tablets 100 mg, 200 mg and 400 mg (SOLIAN)

Approved

Head of Department of the State Control of Medicines and Medical Equipment

Approved by the Pharmacological Committee of the RF Ministry of Health

Dosage Form:

100 and 200 mg tablets

400 mg film-coated tablets

Solian tablets 100 mg and 200 mg:

Active substance: 100 mg amisulpride

amisulpride 200 mg.

Excipients: potato starch, lactose monohydrate, methylcellulose, aqueous colloidal silica, magnesium stearate.

The tablets covered with a shell Solian 400 mg:

Active substance: 400 mg amisulpride

Excipients: sodium amylopectin glycolate, lactose monohydrate, MCC, hypromellose, magnesium stearate, polyoxides 40 stearate, titanium dioxide (E 171).

Description

Solian divisible tablets 100 mg and 200 mg:

White or almost white, flat divisible tablets engraved.

Solian 400mg tablets:

White oblong divisible tablets, film-coated.

Pharmacotherapeutic group: antipsychotic / PBX N05AL05.

pharmacological properties

pharmacodynamics

Amisulpride selectively binds with high affinity to subtypes D2 / D-3 dopaminergic receptor, whereas no affinity for subtypes D1, D4 and D5.

Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonin, histamine H1, alpha adrenergic and cholinergic receptors. Besides amisulpride does not bind to sigma sites.

When used in high doses in animals it blocks postsynaptic D2 receptors localized in the limbic structures, unlike similar striatal receptors. It does not cause catalepsy and do not lead to the development of hypersensitivity D2-dopamine receptors after repeated treatments.

At low doses, it largely blocks the presynaptic D2 / D3 receptors, causing release of dopamine, is responsible for its effects disingibitornye.

This pharmacological profile of atypical may explain amisulpride antipsychotic effect in high doses, due to the advancing blockade of postsynaptic dopamine receptors and its effectiveness against negative symptoms in low doses caused by the blockade of the presynaptic dopamine receptors.

Furthermore, amisulpride causes less extrapyramidal side effects that may be related to its preferential limbic activity.

In clinical studies of schizophrenic patients with acute attacks of Solian significantly facilitated as secondary negative symptoms and affective symptoms such as depressed mood and retardation.

Pharmacokinetics

In humans, amisulpride shows two absorption peaks: one achieved quickly, at 1 h after dosing, and the second - after 3-4 hours after administration. Plasma concentration is respectively 39 ± 3 and 54 ± 4 ng / ml after dose - 50 mg. The volume of distribution of 5.8 l / kg. Since binding to plasma proteins is low (16%), interaction with other drugs is unlikely.

The absolute bioavailability is 48%. Amisulpride is weakly metabolized: 2 inactive metabolite were approximately 4% of the dose was identified. Accumulation amisulpride does not occur, and its pharmacokinetics remains unchanged after administration of repeated doses. T1 / 2 amisulpride is approximately 12 hours after receiving the oral dose. Amisulpride is excreted in the urine in unchanged form. The on / in the introduction of 50% of the dose excreted in the urine, with 90% of this amount excreted within the first 24 hours. Renal Cl is approximately 20 l / h or 330 ml / min.

Carbohydrate-rich meal (containing 68% fluids) significantly decreases the AUC (area under the curve), Tmax and Cmax of amisulpride but no changes were observed after a fatty meal. However, the significance of these observations in everyday clinical practice is unknown.

Liver failure. Due to the fact that the drug is poorly metabolized, there is no need to reduce the dosage in patients with impaired work

liver.

Renal insufficiency. T1 / 2 in patients with renal insufficiency is not changed, but the system Cl reduced by a factor of 2.5 to 3. The AUC of amisulpride at low renal failure is doubled, and almost tenfold (see. "Dosage and Administration") at a moderate failure. Practical experience, however, is limited and there are no results for use doses greater than 50 mg.

Amisulpride is weakly dialysed. A limited number of pharmacokinetic data for the elderly (65 years) patients shows that after a single oral dose of 50 mg growth occurs Cmax, T1 / 2 and AUC 10-30%. Data on repeated doses are not available.

Indications

Amisulpride is prescribed for the treatment of acute and chronic schizophrenic disorders accompanied by pronounced positive (eg, delusions, hallucinations, thought disorders) and / or negative (eg, affective dullness, lack of emotion and avoiding intercourse) symptoms, including for patients with predominantly negative symptoms.

Dosing and Administration

For acute psychotic episodes, it is recommended the use of an oral dose of 400 to 800 mg / day. In some cases, the daily dose may be increased up to 1200 mg / day. Doses exceeding 1200 mg / day, were not sufficiently investigated for security reasons, and therefore they should not be used. There is no need for special treatment in the early titration amisulpride. Doses should be set taking into account the individual response.

For patients with mixed positive and negative symptoms the dose should be selected so as to provide optimal control of the positive symptoms.

Maintenance treatment should be established individually on the minimum level effective doses.

For patients with predominantly negative symptoms designation recommended oral dose of 50 to 300 mg / day. The selection of doses should be individualized.

At doses greater than 400 mg / day amisulpride should be administered in two divided doses.

Elderly patients amisulpride should be used with special caution because of a possible risk of hypotension or sedation.

Babies amisulpride not shown up to 15 years, because the safety of its use has not been established.

In renal insufficiency: Amisulpride excretion via the kidneys. In renal insufficiency, the dose should be reduced to half of patients with creatinine Cl (CRCL) 30 -60 mL / min and up to a third of patients (CRCL) from 10 to 30 ml / min.

Since there is no experience with the drug in patients with severe renal impairment (CRCL & le 10 ml / min), that in their case requires special care (see. "Special Instructions").

Violations of the liver. Since the drug is weakly metabolised, dose reduction is required.

Side effects

As a result of controlled clinical trials identified a number of side effects. It should be noted that in some cases it may be difficult to distinguish from the side effects of symptoms of underlying disease.

Common side effects (5 - 10%): insomnia, anxiety, excitement.

Less common side effects (0.1 - 5%): drowsiness, gastrointestinal disorders such as constipation, nausea, vomiting, dry mouth.

In general, like other neuroleptics, amisulpride causes an increase in prolactin levels in plasma, which is returned to its previous value after discontinuation of the drug. This may cause galactorrhea, amenorrhea, gynecomastia, breast pain, orgasmic dysfunction and impotence.

During therapy amisulpride can increase body weight.

May develop acute dystonia (spasmodic torticollis, oculogyric crises, lockjaw). This condition is reversible without canceling amisulpride, with the help of anti-money. The incidence of extrapyramidal symptoms, which depend on the dose, remains very low in the treatment of patients with predominantly negative symptoms doses of 50-300 mg / day.

Reports of tardive dyskinesia characterized by rhythmical, involuntary movements mainly language and / or persons are usually in cases of prolonged use of the drug. Antiparkinsonian agents are ineffective, they may cause a worsening of symptoms.

From time to time there are reports of hypotension and bradycardia, as well as individual cases of QT prolongation and - very rarely - about atrial fibrillation.

Occasionally reports of allergic reactions, increased liver enzymes, mainly transaminases and cases of seizures.

There are very rare reports of neuroleptic malignant syndrome (see. "Special Instructions").

Contraindications

• Hypersensitivity to the active ingredient of the drug or its other components.
  
• Related prolaktinzavisimye tumors, such as pituitary gland prolactinoma and cancer chest.
  
• Pheochromocytoma.
  
• Children under the age of puberty.
  
• Lactation.
  

Combinations of the following drugs, which can cause atrial fibrillation:

Class Ia antiarrhythmic drugs such as quinidine, disopyramide

Class III antiarrhythmic drugs such as amiodarone, sotalol

Other medications such as bepridil, cisapride, sultopride, thioridazine, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, sparfloxacin.

combination with levodopa (see. "Interaction").

Interaction with other drugs

Contraindicated in combination. Combinations which can cause atrial fibrillation:

• Class Ia antiarrhythmic drugs such as quinidine, disopyramide.
  
• Class III antiarrhythmic drugs such as amiodarone, sotalol.
  
• Other medications such as bepridil, cisapride, sultopride, thioridazine, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, sparfloxacin.
  

Levodopa: reciprocal antagonism of the action of levodopa and neuroleptics.

An incorrect combination. Amisulpride may enhance the central effects of alcohol.

Combinations requiring caution. Drugs that increase the risk of atrial fibrillation:

• Drugs that cause bradycardia, such as beta-blockers, calcium channel blockers, that cause bradycardia, such as diltiazem and verapamil, clonidine, guanfacine digitalis preparations
  
• Drugs that can cause hypokalemia: kaliyvyvodyaschie diuretics, stimulant laxatives, intravenous Amphotericin B, glucocorticoids, tetrakozaktid.
  

Hypokalemia should be adjusted.

Antipsychotics such as pimozide, haloperidol antidepressants such as imipramine lithium.

Combinations to be taken into account:

• CNS depressants, including narcotics, analgesics, sedatives H1- antihistamines, barbiturates, benzodiazepines and other anxiolytics drugs clonidine and its derivatives
  
• Antihypertensive agents and other antihypertensives.
  

Pregnancy and lactation

Pregnancy. In experiments on animals, amisulpride did not show direct toxicity in the offspring. A decrease in fertility linked to the pharmacological effects of the drug (the effect mediated by prolactin). Teratogenic effects of amisulpride were noted. Safety amisulpride during human pregnancy has not been established. Therefore, the use of the drug during pregnancy is not recommended, except in cases where the benefit justifies the potential risk.

Lactation. It is not known whether amisulpride passes into breast milk, so breast-feeding is contraindicated.

Overdose

Experience with amisulpride overdose is limited. It is reported to strengthen the known pharmacological effects of the drug. These include drowsiness and sedation, coma, hypotension and extrapyramidal symptoms.

In cases of acute overdose should suggest the possibility of an interaction of several drugs.

Since amisulpride is weakly dialyzed, hemodialysis should not be used to remove the drug. No specific antidote to amisulpride does not exist. Therefore, it is necessary to take appropriate support measures recommended strict monitoring of vital functions and continuous monitoring of the condition of the heart (the risk of prolongation of the QT interval) until the restoration of the patient's condition. In case of severe extrapyramidal symptoms, should be appointed

anticholinergics.

Special instructions

As with other antipsychotics, may develop neuroleptic malignant syndrome, characterized by hyperthermia, muscle rigidity, dysfunction of the peripheral nervous system, elevated levels of creatine phosphokinase. With the development of hyperthermia, especially during treatment with high doses, all antipsychotic drugs including amisulpride should be repealed.

Withdrawal amisulpride carried kidneys. In the case of serious violations of renal function should be to reduce the dose and use of intermittent regimens (see. "Dosage and administration").

Amisulpride may lower the seizure threshold. Therefore patients with a history of epilepsy should be kept under special observation during treatment amisulpride.

In the elderly amisulpride, like other neuroleptics, should be used with special caution because of a possible risk of hypotension or sedation. In the case of Parkinson's disease, as the application of other antidofaminergicheskih preparations for the appointment of amisulpride, care should be taken because of the possible deterioration of the state. Amisulpride should be used only if neuroleptic treatment can not be avoided.

Prolongation of the QT interval. Amisulpride causes dose-dependent prolongation of the QT interval. It is known that this effect increases the risk of serious ventricular arrhythmias such as atrial fibrillation, and it is amplified in the presence of bradycardia, hypokalemia, congenital or acquired long interval QT. Before prescribing the drug, and, if possible, depending on the clinical status of the patient, it is recommended to monitor factors which could favor the development of cardiac arrhythmias:

• Bradycardia less than 55 beats / min.
  
• Hypokalemia,
  
• Congenital prolongation of the interval QT,
  
• The current use of drugs that may cause severe bradycardia (less than 55 beats / min.), Hypokalemia, decreased cardiac conduction, or prolongation of the interval QT (see section "Interactions".).
  

Effects on ability to drive and perform work requiring special attention. Even in the case of use according to the recommendations amisulpride can affect the reaction rate, resulting in ability to drive or operate machinery may be impaired.

Release Form

Table 30. Blister PVC / aluminum foil.

Storage conditions

Store at temperatures below 25 & ° C and out of reach of children.

Shelf life

3 years.

Do not take the medicine after the expiry date stated on the package.