Solian, pills 200mg, 30pcs

Composition

1 tablet contains:

Active ingredient:

amisulpride 200 mg,

excipients:

potato starch,

lactose monohydrate,

methylcellulose,

colloidal aqueous silicon dioxide,

magnesium stearate

Pharmacological action

Solian – antipsychotic agent (neuroleptic)

Pharmacodynamics

Amisulpride binds selectively and with high affinity to the D2/D3 subtypes of dopaminergic receptors, while it does not have affinity for the D1, D4 and D5 subtypes.

Unlike classical and atypical antipsychotics, amisulpride has no affinity for serotonin, histamine H1, alpha-adrenergic and cholinergic receptors. In addition, amisulpride does not bind to sigma sites. When used in high doses, it blocks postsynaptic D2 receptors localized in limbic structures, unlike similar striatum receptors. It does not cause catalepsy and does not lead to the development of hypersensitivity of D2-dopamine receptors after repeated treatment.

At low doses, it predominantly blocks presynaptic D2/D3 receptors, causing the release of dopamine responsible for its disinhibitory effects. This atypical pharmacological profile may explain the high-dose antipsychotic effect of amisulpride resulting from postsynaptic dopamine receptor blockade, and its effectiveness against negative symptoms at low doses resulting from presynaptic dopamine receptor blockade. In addition, amisulpride is less likely to cause extrapyramidal side effects, which may be due to its predominant limbic activity.

In patients with schizophrenia with acute attacks, Solian acts on both secondary negative symptoms and affective symptoms, such as depressive mood and retardation.

Pharmacokinetics

Amisulpride has two absorption peaks: one is reached quickly, one hour after use of the dose, and the second – between 3 and 4 hours after use. The plasma concentration is 39 ± 3 and 54 ± 4 ng/ml, respectively, after taking 50 mg. The volume of distribution is 5,8 l/kg. Since plasma protein binding is low (16%), interactions with other drugs are unlikely.

Absolute bioavailability is 48%. Amisulpride is poorly metabolized: (about 4%, two inactive metabolites were identified. Accumulation of amisulpride does not occur, and its pharmacokinetics remain unchanged after repeated doses. The half-life (T 1/2) of amisulpride is approximately 12 hours after taking the oral dose. Amisulpride is excreted unchanged in the urine. Renal clearance is approximately 20 l/hr or 330 ml/min. Carbohydrate-rich food (containing 68% liquid) significantly reduces the AUC (area under the concentration/time curve), the time to reach the maximum concentration, and the maximum concentration of amisulpride itself, but no changes in pharmacokinetics were observed after taking fatty foods. 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 dose for patients with impaired liver function.

Kidney failure. T 1/2 in patients with renal insufficiency does not change, but the systemic clearance decreases with a coefficient from 2.5 to 3. The AUC of amisulpride in small renal insufficiency doubles, and in moderate insufficiency almost tenfold (see the section Dosage and use). Practical experience, however, is limited, and there are no results on the use of doses exceeding 50 mg.

Amisulpride is poorly dialyzed.

A limited number of pharmacokinetic data for elderly (over 65 years of age) patients indicate that after a single oral dose of 50 mg, Cmax, T1 / 2 and AUC are 10-30% higher than in younger people. Data on the pharmacokinetics of the drug during long-term treatment are not available.

Indications

Treatment of acute and chronic schizophrenia accompanied by pronounced productive (for example: delusions, hallucinations, thinking disorders) and/or negative (for example: affective flatness, lack of emotionality, and withdrawal from communication) disorders, including patients with a predominance of negative symptoms.

Use during pregnancy and lactation

The safety of taking amisulpride during pregnancy has not been established.

Therefore, the use of the drug during pregnancy is not recommended, except in cases where the expected benefit to the mother justifies the potential risk to the fetus.

Although there are no reported cases of side effects in newborns, theoretically, amisulpride, if used at the end of pregnancy and in high doses, can cause side effects in newborns (atropine-like effects: tachycardia, hyperreflexia, bloating, slowing the discharge of meconium; extrapyramidal symptoms: hypertonus, tremor, sedation), and therefore they may need appropriate monitoring.

It is not known whether amisulpride is able to enter breast milk, so breast-feeding while taking it is contraindicated.

Contraindications

• Hypersensitivity to the Active ingredient of the drug or to other components of Solian.
• Concomitant prolactin-dependent tumors, such as pituitary prolactinoma and breast cancer.
• Pheochromocytoma.
• Children’s age (up to 14 years).
• Breast-feeding.
• Combinations with the following medications that may contribute to the development of atrial fibrillation: quinidine, disopyramide, amiodarone, sotalol, as well as with bepridil, cisapride, sultopride, thioridazine, erythromycin, vincamine, halofantrine, pentamidine, sparfloxacin.
• Combination with levodopa. (see section “Interaction with other medicinal products”).

With caution-pregnancy, epilepsy, Parkinsonism, old age, kidney failure.

Side effects

Side effects are presented according to the following frequency gradations: very common (>10%), common (>>1%,0,1%,0,01%, >>

Side effects observed in controlled clinical trials and post-marketing use of the drug are listed below. It should be noted that in some cases it is very difficult to differentiate side effects from symptoms of the underlying disease.

Nervous system disorders: very often — extrapyramidal symptoms (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia). These symptoms are usually mild when taken at optimal doses and partially reversible when anticholinergic antiparkinsonian drugs are added without discontinuing amisulpride treatment. The frequency of extrapyramidal symptoms depends on the dose. Therefore, in patients with predominantly negative symptoms, taking amisulpride at a dose of 50-300 mg, the incidence of extrapyramidal disorders is very low; often — acute dystonia (spastic torticollis, oculogyric crises, trismus), reversible with the addition of anticholinergic Antiparkinsonian drugs without stopping treatment with amisulpride; daytime drowsiness; infrequently — tardive dyskinesia, characterized by rhythmic, involuntary movements mainly of the tongue and tongue. /or facial muscles that usually occur after prolonged use of the drug. Anticholinergic antiparkinsonian drugs in these cases are ineffective or may increase symptoms; seizures; unknown frequency-neuroleptic malignant syndrome (see “Special instructions”).

From the gastrointestinal tract: often-constipation, nausea, vomiting, dry mouth.

From the endocrine system: often-amisulpride causes an increase in plasma prolactin concentrations, reversible after discontinuation of the drug. This can lead to galactorrhea, amenorrhea, gynecomastia, breast pain, and erectile dysfunction.

Metabolic disorders: often-weight gain; infrequently-hyperglycemia (see “Contraindications, ” With caution ” and “Special instructions”).

Disorders of the cardiovascular system: often-hypotension; infrequently — bradycardia; unknown frequency — prolongation of the QT interval; ventricular arrhythmias, such as polymorphic ventricular tachycardia of the “pirouette” type (torsade de pointes), which can develop into ventricular fibrillation and lead to cardiac arrest and sudden death (see “Special instructions”); thromboembolism, including pulmonary embolism, sometimes fatal and deep vein thrombosis (see “Special instructions”).

From the laboratory parameters: infrequently-increased levels of liver enzymes, mainly transaminases.

Immune system disorders: infrequently-allergic reactions.

Others: often — insomnia, anxiety, agitation, orgasmic disorders, frigidity.

Interaction

Contraindicated combinations

Combinations that can cause ventricular arrhythmia of the “pirouette”type:

• 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: mutual antagonism of levodopa and neuroleptics.

Not recommended combinations Amisulpride increases the depressing effect on the central nervous system of alcohol.

Combinations that require special caremedicines that increase the risk of ventricular arrhythmia of the “pirouette”type:Drugs that cause bradycardia, such as beta-blockers, calcium channel blockers that cause bradycardia (diltiazem and verapamil), clonidine, guanfacine; digitalis preparations. Drugs that may cause hypokalemia: potassium-releasing diuretics, laxatives, amphotericin B, glucocorticoids, tetracosactides (hypokalemia should be corrected). Antipsychotics such as pimozide, haloperidol; antidepressants such as imipramine; lithium.

Combinations that should be taken into consideration Combination with drugs that depress the central nervous system, including narcotic analgesics, antipsychotic drugs (neuroleptics), antihistamines with sedative effect, barbiturates, benzodiazepines and other anxiolytic drugs, a pronounced increase in the depressive effect. With antihypertensive drugs-increased antihypertensive effect.

How to take, course of use and dosage

In acute psychotic episodes, oral use is recommended at a dose of 400 to 800 mg per day. In some cases, the daily dose may be increased to 1200 mg per day.

Doses should be increased according to individual tolerance.

The safety of doses exceeding 1200 mg / day has not been sufficiently investigated, so they should not be used.

For patients with mixed negative and productive symptoms, doses should be selected to ensure optimal control of productive symptoms.

Maintenance treatment should be set individually at the minimum effective dose level.

For patients with a predominance of negative symptoms, oral use is recommended at a dose of 50 to 300 mg per day. The selection of doses should be individual.

In doses exceeding 400 mg per day, Amisulpride should be administered in 2 divided doses.

Elderly patients: Amisulpride should be prescribed with special precautions due to the possible development of hypotension or excessive sedation.

Renal failure: Amisulpride is excreted through the kidneys. In patients with renal insufficiency, the dose for patients with a creatinine clearance (CRCL) of 30-60 ml/min should be reduced by half and to 1/3 for patients with a CRCL of 10 to 30 ml/min.

Overdose

Symptoms: Experience with amisulpride overdose is very limited. A significant increase in the known pharmacological effects of the drug, namely the development of drowsiness, sedation, coma, hypotension and extrapyramidal symptoms, has been reported.

It should be borne in mind that overdose phenomena may occur in cases of erroneous use of additional doses of the drug or simultaneous use of other drugs.

Treatment: There is no specific antidote for amisulpride.

In case of overdose, the main vital functions of the body should be monitored and maintained until the patient completely comes out of the overdose state. In case of overdose, ECG monitoring is mandatory, since there is a risk of prolongation of the QT interval and the development of life-threatening rhythm disorders (see “Side effect”).

In case of severe extrapyramidal symptoms, anticholinergic agents should be used.

Since the elimination of amisulpride by hemodialysis is insignificant, the use of hemodialysis for its elimination in overdose is impractical.

Special instructions

According to a controlled double-blind study comparing amisulpride and haloperidol in patients with acute schizophrenia (191 patients), a significantly greater reduction in secondary negative symptoms was observed with the use of amisulpride. According to clinical studies, when using amisulpride, there was a significantly lower incidence of extrapyramidal symptoms than when using haloperidol.

As with other antipsychotics, amisulpride (especially high doses) may cause neuroleptic malignant syndrome characterized by hyperthermia, muscle rigidity, autonomic disorders, and elevated creatine phosphokinase levels. All antipsychotic medications, including amisulpride, should be discontinued if hyperthermia develops, especially when high doses of neuroleptics are used.

Caution should be exercised when prescribing anti-dopaminergic drugs, and in particular amisulpride, for Parkinson’s disease, since its use may worsen the course of this disease. In patients with Parkinson’s disease, amisulpride should only be used if its use cannot be avoided. If a patient with Parkinson’s disease receiving dopaminergic agonists needs treatment with amisulpride, then dopaminergic agonists should be discontinued gradually (by gradually reducing the dose until they are completely discontinued), since abrupt withdrawal can lead to the development of neuroleptic malignant syndrome.

Anticholinergic antiparkinsonian drugs (rather than dopaminergic agonists) should be used to correct extrapyramidal symptoms that occur during treatment with amisulpride.

Due to the fact that amisulpride causes a dose-dependent increase in the duration of the QT interval, taking it increases the risk of developing paroxysmal tachycardia, including potentially life-threatening polymorphic ventricular tachycardia of the “pirouette” type (torsade de pointes). Therefore, if the patient’s condition allows, before prescribing amisulpride, it is recommended to take an ECG and examine the blood electrolyte composition, identify and, if possible, correct factors that may contribute to dangerous rhythm disorders (bradycardia less than 55 beats/min, hypokalemia, hypomagnesemia, congenital or acquired prolonged QT interval, simultaneous use of drugs that can cause severe bradycardia (less than 55 beats/min), hypokalemia, slowing of intracardiac conduction, prolongation of the QT interval) (see “Interaction”).

Alcohol and alcohol-containing medications should not be taken during amisulpride treatment.

Due to the ability of the drug to lower the threshold of convulsive readiness, when taking amisulpride in patients with epilepsy, they should be carefully monitored clinically and, if possible, by EEG.

Some atypical antipsychotics, including amisulpride, can cause an increase in blood glucose concentrations. In patients with diabetes mellitus and patients with risk factors for diabetes mellitus, blood glucose levels should be regularly monitored when prescribing amisulpride.

In elderly patients, amisulpride, like other antipsychotics, should be used with extreme caution because of the possible risk of hypotension or excessive sedation.

In randomized clinical trials conducted in a group of elderly patients with dementia treated with certain atypical antipsychotic drugs, compared with placebo, there was a threefold increase in the risk of developing cerebrovascular events (acute cerebrovascular disorders). The mechanism of this increased risk is unknown. An increase in this risk cannot be excluded with other antipsychotic medications or in other patient groups. Amisulpride should be used with caution in patients with risk factors for stroke.

Elderly patients with dementia-related psychoses have been shown to have an increased risk of death when treated with antipsychotic drugs. An analysis of 17 placebo-controlled trials (with an average duration of more than 10 weeks) showed that the majority of patients treated with atypical antipsychotic medications had a 1.6-1.7-fold greater risk of death than patients treated with placebo. Although the causes of death in clinical trials with atypical antipsychotic medications varied, most of the causes of death were either cardiovascular (e. g. heart failure, sudden death) or infectious (e. g. pneumonia) in nature. Observational studies have confirmed that, similar to treatment with atypical antipsychotics, treatment with conventional antipsychotics can also increase mortality. The extent to which the increase in mortality may be due to the antipsychotic drug, rather than some patient characteristics, is unclear.

Venous thromboembolism, sometimes fatal, has been reported with antipsychotic medications. Therefore, amisulpride should be used with caution in patients with risk factors for thromboembolism (see “Side effects”).

Amisulpride is excreted by the kidneys. If renal function is impaired, the dose of the drug should be reduced (see “Dosage and use”).

Influence on the ability to drive vehicles or other mechanisms. Patients, especially those who are drivers of vehicles or people working with mechanisms, should be informed about the possibility of drowsiness and reduced psychomotor reactions while taking amisulpride, especially at the beginning of treatment, as this can be dangerous when driving vehicles and working with mechanisms.

Form of production

Tablets

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Amisulpride

Conditions of release from pharmacies

By prescription

Dosage form

Tablets