INSTRUCTIONS for MEDICAL USE of the medicinal product SОLERON 100 (SOLERON 100) SОLERON 200 (SOLERON 200)

Composition:

Active substance: amisulpride;

1 tablet contains 100 mg or 200 mg of amisulpride;

Excipients: lactose monohydrate; microcrystalline cellulose; hydroxypropylmethylcellulose; sodium croscarmellose; colloidal anhydrous silicon dioxide; magnesium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: white or almost white tablets, convex on both sides, round-shaped, with a score line on one side.

Pharmacotherapeutic group. Antipsychotic agents. ATC code N05A L05.

Pharmacological properties.

Pharmacodynamics.

Amisulpride is an antipsychotic agent belonging to the substituted benzamides class. Its pharmacodynamic properties are characterized by selective and predominant affinity for D2 and D3 receptors in the limbic system. Amisulpride has no affinity for serotonin receptors or other neurotransmitter receptors such as histamine, cholinergic, or adrenergic receptors.

In animal studies at high doses, amisulpride preferentially blocks dopaminergic neurons of the mesolimbic system compared to those in the striatal system. This specific receptor affinity explains the favorable antipsychotic effects of amisulpride over its extrapyramidal side effects.

At low doses, amisulpride preferentially blocks presynaptic dopaminergic D2 and D3 receptors, which explains its effect on negative symptoms.

It has been demonstrated in a controlled, double-blind clinical trial comparing amisulpride with haloperidol in 191 patients with acute schizophrenia that amisulpride significantly improved secondary negative symptoms more than haloperidol.

Pharmacokinetics.

In humans, amisulpride shows two absorption peaks: the first occurs rapidly, 1 hour after dose administration, and the second after 3–4 hours. Plasma concentration levels are 39±3 and 54±4 ng/mL, respectively, after a 50 mg dose.

The volume of distribution is 5.8 L/kg. Plasma protein binding is low (16%), making interactions with other drugs due to protein binding unlikely. Absolute bioavailability is 48%.

Amisulpride undergoes minimal metabolism: two inactive metabolites have been identified, accounting for approximately 4% of the administered dose.

Amisulpride does not accumulate in the body, and its pharmacokinetics remain unchanged after repeated dosing. The elimination half-life after oral administration is approximately 12 hours.

Amisulpride is excreted unchanged in urine. 50% of an intravenously administered dose is excreted in urine, of which 90% is excreted within the first 24 hours.

Renal clearance is approximately 330 mL/min.

A carbohydrate-rich meal significantly reduces the AUC, Tmax, and Cmax of amisulpride, whereas fat-rich meals do not cause significant changes. The clinical relevance of these changes during amisulpride treatment is unknown.

Hepatic impairment. Since amisulpride undergoes negligible metabolism, dose adjustment is not necessary in patients with hepatic impairment.

Renal impairment. In patients with renal impairment, the elimination half-life does not change, while systemic clearance is reduced by 2.5–3 times.

The AUC of amisulpride is doubled in mild renal impairment and increased nearly 10-fold in moderate renal impairment.

Clinical experience is limited, and data on doses above 50 mg are lacking.

Amisulpride is poorly dialyzed.

Elderly patients. Available pharmacokinetic data indicate that after a single 50 mg dose, Cmax, T1/2, and AUC values are 10–30% higher in patients aged 65 years and older. Data on repeated dosing are lacking.

Preclinical safety data.

The toxicological profile of amisulpride is determined by the pharmacological effects of the compound. Repeated-dose toxicity studies did not reveal any target organ toxicity. In animal studies, amisulpride affected fetal growth and intrauterine development at doses corresponding to a human equivalent dose of 2000 mg/day and higher in patients weighing 50 kg. There is no evidence indicating that amisulpride has teratogenic potential. No studies evaluating the effects of amisulpride on offspring behavior have been conducted.

Carcinogenicity studies showed hormonally dependent tumors in rodents. These findings have no clinical relevance for humans.

In animals, reduced fertility was observed, related to the pharmacological properties of the compound (prolactin-mediated effects).

Clinical characteristics.

Indications.

Treatment of schizophrenia.

Contraindications.

Hypersensitivity to the active substance or to any component of the medicinal product.
Serious episodes of arterial hypertension have been reported in patients with pheochromocytoma who were treated with antidopaminergic agents, including certain benzamides. Therefore, this medicinal product must not be administered to patients with diagnosed or suspected pheochromocytoma.
Age under 15 years (due to lack of clinical data).
Diagnosed or suspected prolactin-dependent tumor, such as prolactinoma of the pituitary gland or breast cancer (see sections "Special precautions for use" and "Side effects").
In combination with citalopram, escitalopram, domperidone, hydroxyzine, piperacine, or non-anti-Parkinsonian dopaminergic agents (cabergoline, quinagolide) (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Sedatives. It should be taken into account that many medicinal products or substances may cause additive depressant effects on the central nervous system (CNS) and contribute to reduced attention. These include morphine derivatives (analgesics, antitussives, and opioid substitution therapy agents), neuroleptics, barbiturates, benzodiazepines, non-benzodiazepine anxiolytics (such as meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1-antihistamines, centrally-acting antihypertensives, baclofen, and thalidomide.

Medicinal products capable of inducing torsades de pointes. This serious arrhythmia may be triggered by a variety of medicinal products, including antiarrhythmics and others. Predisposing factors include hypokalemia, bradycardia, or pre-existing congenital or acquired QT interval prolongation.

This particularly applies to Class IA and Class III antiarrhythmic agents, as well as certain neuroleptics. This effect may also be induced by other compounds not belonging to these classes.

For dolasetron, erythromycin, spiramycin, and vinpocetine, this interaction applies only to intravenous formulations.

In general, concomitant use of a medicinal product that may induce torsades de pointes with another agent having the same effect is contraindicated.

However, some of these agents are exceptions because their use cannot always be avoided; therefore, their concomitant use with agents capable of inducing torsades de pointes is not recommended. This includes methadone, hydroxychloroquine, antiparasitic agents (chloroquine, halofantrine, lumefantrine, pentamidine), and neuroleptics.

However, citalopram, escitalopram, domperidone, hydroxyzine, and piperacine are not among these exceptions, and their concomitant use with any agent capable of inducing torsades de pointes is contraindicated.

Contraindicated combinations.

Dopamine agonists, except anti-Parkinsonian agonists (cabergoline, quinagolide). Mutual antagonism of effects between dopamine agonists and neuroleptics.

Citalopram, escitalopram, domperidone, hydroxyzine, piperacine. Increased risk of ventricular arrhythmias, particularly torsades de pointes.

Combinations not recommended.

Antiparasitic agents capable of inducing torsades de pointes (chloroquine, halofantrine, lumefantrine, pentamidine). Increased risk of ventricular arrhythmias, including torsades de pointes. If possible, one of the two agents should be discontinued. If this combination cannot be avoided, QT monitoring prior to treatment and ECG monitoring during treatment are recommended.

Dopaminergic anti-Parkinson agents (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, rasagiline, ropinirole, rotigotine, selegiline, tolcapone). Mutual antagonism of effects between dopamine agonists and neuroleptics. Dopamine agonists may provoke or exacerbate psychotic disorders. When neuroleptic treatment is necessary in a patient with Parkinson's disease who is receiving dopamine agonists, the dose of dopamine agonists should be gradually reduced and then discontinued (abrupt withdrawal of dopaminergic agents may precipitate neuroleptic malignant syndrome).

Other medicinal products that may induce torsades de pointes: Class IA antiarrhythmics (quinidine, hydroquinidine, disopyramide) and Class III antiarrhythmics (amiodarone, dronedarone, sotalol, dofetilide, ibutilide), as well as other agents such as arsenic compounds, difemanil, intravenous dolasetron, intravenous erythromycin, levofloxacin, mequitazine, mizolastine, prucalopride, intravenous vinpocetine, moxifloxacin, intravenous spiramycin, vandetanib, toremifene. Increased risk of ventricular arrhythmias, including torsades de pointes.

Other neuroleptics capable of inducing torsades de pointes (chlorpromazine, thiamine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperone, pipotiazine, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, including torsades de pointes.

Alcohol (as a beverage or as an excipient). Alcohol enhances the sedative effect of neuroleptics. Reduced attention may make driving and operating machinery hazardous. Consumption of alcoholic beverages and use of medicinal products containing alcohol should be avoided.

Levodopa. Mutual antagonism of effects between levodopa and neuroleptics. Patients with Parkinson's disease should receive the lowest effective doses of each agent.

Methadone. Increased risk of ventricular arrhythmias, including torsades de pointes.

Sodium oxybate. Enhanced central nervous system depression. Reduced attention may pose a danger when driving or operating machinery.

Hydroxychloroquine. Increased risk of ventricular arrhythmia, particularly torsades de pointes.

Combinations requiring precautions.

Anagrelide. Increased risk of ventricular arrhythmia, especially torsades de pointes. Clinical and electrocardiographic monitoring are required during concomitant use.

Azithromycin, clarithromycin, ciprofloxacin, levofloxacin, norfloxacin, roxithromycin. Increased risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and ECG monitoring are required during concomitant use.

Beta-blockers in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol). Increased risk of ventricular arrhythmias, particularly torsades de pointes. In addition, there is a vasodilatory effect and risk of arterial hypotension, especially orthostatic (additive effect). Clinical and ECG monitoring are required.

Medicinal products that slow heart rate (especially Class IA antiarrhythmics, beta-blockers, certain Class III antiarrhythmics, certain calcium channel blockers, digitalis glycosides, pilocarpine, anticholinesterase agents). Increased risk of ventricular arrhythmias, particularly torsades de pointes. Clinical and ECG monitoring are required.

Medicinal products that reduce potassium concentration (potassium-depleting diuretics, alone or in combination, stimulant laxatives, glucocorticoids, tetracosactide, and intravenous amphotericin B). Increased risk of ventricular arrhythmias, including torsades de pointes. Any hypokalemia should be corrected before initiating treatment with amisulpride, and clinical status, electrolyte balance, and ECG should be monitored.

Lithium. Risk of neuro-psychiatric signs suggestive of neuroleptic malignant syndrome or lithium toxicity. Regular clinical monitoring and laboratory testing are indicated, especially at the beginning of concomitant therapy.

Ondansetron. Increased risk of ventricular arrhythmia, particularly torsades de pointes. Clinical and electrocardiographic monitoring are required during concomitant use.

Combinations to be considered.

Other sedative agents. Enhanced CNS depression. Impaired ability to concentrate may make driving and operating machinery hazardous.

Orlistat. Risk of reduced therapeutic effect when used concomitantly with orlistat.

Special precautions for use.

Potentially fatal neuroleptic malignant syndrome. As with other neuroleptics, neuroleptic malignant syndrome, which may lead to fatal outcomes, can occur. It is characterized by hyperthermia, muscle rigidity, autonomic dysfunction, altered consciousness, rhabdomyolysis, and elevated serum creatine phosphokinase (CPK) levels. In case of hyperthermia, especially when high doses are used, all antipsychotic drugs, including amisulpride, must be discontinued.

Rhabdomyolysis has also been observed in patients without neuroleptic malignant syndrome.

QT interval prolongation. Amisulpride may cause dose-dependent QT interval prolongation on ECG, increasing the risk of serious ventricular arrhythmias such as torsades de pointes. The risk of developing serious ventricular arrhythmias is increased in the presence of bradycardia, hypokalemia, congenital or acquired prolonged QT interval (e.g., when combined with drugs that prolong the QTc interval) (see section "Undesirable effects").

If the clinical situation allows, it is recommended before initiating treatment to ensure the absence of factors that may predispose to this rhythm disturbance, such as heart rate below 55 beats/min, hypokalemia, congenital prolonged QT interval, or concomitant use of drugs that may cause marked bradycardia (< 55 beats/min), hypokalemia, reduced cardiac conduction, or QTc prolongation (see sections "Contraindications" and "Interaction with other medicinal products and other forms of interaction").

For patients requiring long-term treatment with neuroleptics, an ECG should be performed before starting therapy.

Stroke. In randomized, placebo-controlled clinical trials involving elderly patients with dementia treated with certain atypical antipsychotics, the risk of cerebrovascular events was three times higher than in the placebo group. The mechanism underlying this increased risk is unknown. An increased risk associated with other antipsychotic agents and risk in other patient populations cannot be ruled out. This medicinal product should be used with caution in patients with risk factors for stroke.

Elderly patients with dementia. In elderly patients with psychosis associated with dementia, treatment with antipsychotic agents increases the risk of mortality. Analysis of 17 placebo-controlled clinical trials (mean duration: 10 weeks), conducted in patients primarily receiving atypical antipsychotics, showed that the risk of death was 1.6 to 1.7 times higher in patients treated with these drugs compared to placebo. After an average treatment duration of 10 weeks, the mortality risk was 4.5% in patients receiving antipsychotics versus 2.6% in the placebo group.

Although the causes of death in clinical trials with atypical antipsychotics were varied, most fatal cases were due to cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) causes.

Observational studies suggest that traditional antipsychotics may also increase mortality, similar to atypical antipsychotics. The relative contribution of antipsychotic drugs and patient-specific factors to increased mortality in epidemiological studies remains unclear.

Venous thromboembolism (VTE). Cases of venous thromboembolism (VTE) have been reported with the use of antipsychotic agents. Since patients receiving antipsychotics often have acquired risk factors for VTE, possible VTE risk factors should be assessed before initiating treatment with Soleron or during such treatment, and preventive measures should be taken (see section "Undesirable effects").

Hyperglycemia/metabolic syndrome. Cases of hyperglycemia or impaired glucose tolerance, as well as the development or worsening of diabetes mellitus, have been reported in patients treated with certain antipsychotic agents, including amisulpride (see section "Undesirable effects").

According to current guidelines, clinical and laboratory monitoring of patients receiving Soleron is necessary. Particular attention should be paid to patients with diabetes or risk factors for developing diabetes.

Seizures. Amisulpride may lower the seizure threshold; therefore, careful monitoring is required in patients with a history of seizures during treatment with amisulpride.

Special patient groups. Since amisulpride is eliminated via the kidneys, the dose should be reduced or alternative treatment considered in patients with renal impairment (see section "Dosage and administration"). Data are lacking for patients with severe renal impairment (see section "Dosage and administration").

As with other antipsychotic agents, amisulpride should be used with particular caution in elderly patients due to the potential risk of sedation and arterial hypotension. Elderly patients may also require dose reduction due to age-related renal impairment (see section "Dosage and administration").

Caution is advised when prescribing amisulpride to patients with Parkinson's disease, as it may worsen the condition. Amisulpride should be used only if treatment with neuroleptics cannot be avoided.

Withdrawal syndrome. Withdrawal symptoms, including nausea, vomiting, and insomnia, have been described following abrupt discontinuation of antipsychotics used at high doses. Relapse of psychotic symptoms and emergence of involuntary movement disorders (such as akathisia, dystonia, and dyskinesia) have been reported with amisulpride use. Therefore, gradual discontinuation of amisulpride is recommended.

Hyperprolactinemia. Amisulpride may increase prolactin levels (see section "Undesirable effects"). Patients with hyperprolactinemia and/or those with potentially prolactin-dependent tumors should be closely monitored during treatment with amisulpride (see section "Contraindications").

Benign pituitary tumor. Amisulpride may increase prolactin levels. Cases of benign pituitary tumors, such as prolactinoma, have been reported during treatment with amisulpride (see section "Undesirable effects"). In cases of very high prolactin levels or clinical signs suggestive of a pituitary tumor (e.g., visual field defects, headache), imaging studies should be performed to evaluate pituitary status. If a pituitary tumor is confirmed, treatment with amisulpride must be discontinued (see section "Contraindications").

Hepatotoxicity. Severe hepatotoxic reactions have been reported during treatment with amisulpride. Patients should be informed that if any signs of liver injury occur—such as asthenia, loss of appetite, nausea, vomiting, abdominal pain, or jaundice—they should seek immediate medical attention. Prompt evaluation, including clinical assessment and liver function tests, should be performed (see section "Undesirable effects").

Other. Leukopenia, neutropenia, and agranulocytosis have been reported with the use of antipsychotics, including amisulpride. Fever or infections of unknown origin may indicate leukopenia (see section "Undesirable effects") and require immediate hematological investigation.

This medicinal product is not recommended for use in combination with alcohol, dopaminergic antiparkinsonian agents, antiparasitic agents capable of provoking torsades de pointes, methadone, levodopa, other neuroleptics, or drugs capable of provoking torsades de pointes, sodium oxybate, or hydroxychloroquine (see section "Interaction with other medicinal products and other forms of interaction").

Precautions related to excipients. This medicinal product contains lactose. Patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

This medicinal product contains 30 or 60 mg of sodium (depending on the Soleron 100 or Soleron 200 dosage). This should be taken into account when calculating the daily sodium intake for patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of amisulpride in pregnant women are limited. Therefore, the safety of amisulpride during pregnancy has not been established.

Amisulpride crosses the placenta.

Animal studies have shown reproductive toxicity (see section "Preclinical safety data").

Amisulpride is not recommended during pregnancy and in women of childbearing potential who are not using effective contraception, except when the benefit outweighs the risk.

Newborns whose mothers received antipsychotics (including amisulpride) during the third trimester of pregnancy are at risk of adverse reactions, including extrapyramidal symptoms and/or withdrawal symptoms of varying severity and duration after birth (see section "Undesirable effects"). Reported adverse reactions include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress syndrome, or feeding difficulties. Therefore, careful monitoring of newborns is required.

Breastfeeding. Amisulpride is excreted in breast milk in considerable amounts, in some cases exceeding 10% of the dose adjusted for maternal weight. However, there are no data on the concentration of amisulpride in infant blood. Information on the effects of amisulpride on neonates/infants is insufficient.

The benefit of breastfeeding for the infant and the benefit of treatment with amisulpride for the mother should be weighed, and a decision made whether to discontinue breastfeeding or to discontinue amisulpride therapy.

Fertility. In animals, reduced fertility associated with the pharmacological effects of the drug (prolactin-mediated effect) has been observed.

Ability to affect reaction speed when driving or operating machinery.

Patients, especially those who drive or operate machinery, should be warned about the risk of drowsiness or blurred vision associated with the use of this medicinal product (see section "Undesirable effects").

Administration and Dosage.

The drug should be administered orally.

If the daily dose does not exceed 400 mg, Soleron should be taken once daily. Doses exceeding 400 mg per day should be divided into two administrations.

Acute psychotic episodes. Treatment may be initiated with intramuscular administration of the drug in the appropriate dosage form for several days at a maximum dose of 400 mg/day, followed by transition to oral administration.

Doses from 400 mg/day to 800 mg/day are recommended to be administered orally. The maximum oral dose must never exceed 1200 mg/day. The safety of doses exceeding 1200 mg/day has not been adequately studied. Therefore, such doses should not be used. Maintenance or dose adjustments must be individually determined according to the patient's response. In all cases, maintenance therapy should be individually prescribed at the lowest effective dose.

Predominantly negative episodes. The drug is recommended to be administered at a dose ranging from 50 mg (using medicinal products of appropriate strength) to 300 mg daily. The dose should be individually adjusted. The optimal dose is approximately 100 mg daily.

Elderly patients. The safety of amisulpride in elderly patients has been evaluated in a limited number of patients. This medicinal product should be used with particular caution in this subgroup due to the risk of developing arterial hypotension and sedative effects. Dose reduction may also be required in patients with renal impairment (see section "Special precautions").

Renal impairment. Since amisulpride is excreted by the kidneys, in patients with renal impairment and creatinine clearance of 30–60 mL/min, the daily dose should be halved, and in patients with renal impairment and creatinine clearance of 10–30 mL/min, reduced to one-third.

Due to limited data in patients with severe renal impairment (creatinine clearance <10 mL/min), careful monitoring of such patients is recommended (see section "Special precautions").

Hepatic impairment. Since the drug is weakly metabolized, dose reduction is not required.

Children.

The safety and efficacy of amisulpride in children from puberty up to 18 years of age have not been established: data on the use of amisulpride in children under 18 years of age with schizophrenia are limited. For this reason, the use of amisulpride in this patient group is not recommended.

Amisulpride is contraindicated in children under 15 years of age, as the safety of this medicinal product in such patients has not yet been established (see section "Contraindications").

Overdose.

Currently, there is limited data on acute amisulpride overdose. Reported signs and symptoms are mainly due to enhanced pharmacological activity, clinically manifesting as somnolence, sedative effects, arterial hypotension, extrapyramidal symptoms, and coma. Fatal cases have been reported, primarily when amisulpride was used concomitantly with other psychotropic agents.

There is no known specific antidote for amisulpride. In case of acute overdose, it should be determined whether other medicinal products were used concomitantly, and appropriate measures should be taken:

close monitoring of vital functions;
cardiac monitoring (risk of QT interval prolongation) until full recovery;
in cases of severe extrapyramidal symptoms, anticholinergic agents should be administered.

Since amisulpride is poorly dialyzed, the effectiveness of hemodialysis for elimination of this medicinal compound is limited.

Adverse Reactions

Adverse effects are classified by frequency according to the following scale: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency not known (cannot be estimated from the available data).

Nervous system disorders. Very common: extrapyramidal symptoms (tremor, hypertonia, hypersalivation, akathisia, hypokinesia, dyskinesia). In most cases, these are mild in nature at maintenance doses and are partially reversible without discontinuation of amisulpride when anticholinergic anti-Parkinson agents are administered.

The frequency of extrapyramidal symptoms, which is dose-dependent, is very low in patients treated for predominantly negative symptoms at doses of 50–300 mg/day.

Common: acute dystonia (spasmodic torticollis, oculogyric crisis, trismus). This is reversible without discontinuation of amisulpride upon administration of an anticholinergic anti-Parkinson agent. Somnolence.

Uncommon: tardive dyskinesia has been reported, characterized by involuntary movements of the tongue and/or facial muscles, usually after long-term treatment. Anticholinergic anti-Parkinson agents are ineffective or may exacerbate symptoms. Seizures.

Rare: neuroleptic malignant syndrome, which may be fatal (see section "Special precautions").

Frequency not known: restless legs syndrome.

Psychiatric disorders. Common: insomnia, anxiety, agitation, frigidity.

Uncommon: confusion.

Gastrointestinal disorders. Common: constipation, nausea, vomiting, dry mouth.

Endocrine disorders. Common: increased plasma prolactin levels, which are reversible upon discontinuation of the drug. This may lead to the following clinical symptoms: galactorrhea, amenorrhea, gynecomastia, breast pain, erectile dysfunction.

Rare: benign pituitary gland tumor, such as prolactinoma (see sections "Contraindications" and "Special precautions").

Metabolism and nutrition disorders. Uncommon: hyperglycemia (see section "Special precautions"), hypertriglyceridemia, and hypercholesterolemia.

Rare: hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Cardiac disorders. Uncommon: bradycardia.

Rare: QT interval prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest, sudden death (see section "Special precautions").

Respiratory, thoracic and mediastinal disorders. Uncommon: nasal congestion, aspiration pneumonia (mainly when used concomitantly with other antipsychotics and agents that suppress CNS function).

Investigations. Common: weight gain.

Uncommon: elevated liver enzymes, primarily transaminases.

Frequency not known: increased blood creatine phosphokinase levels.

Immune system disorders. Uncommon: allergic reactions.

Eye disorders. Common: blurred vision (see section "Ability to influence reaction rate when driving or operating machinery").

Hepatobiliary disorders. Uncommon: hepatocellular injury.

Skin and subcutaneous tissue disorders. Rare: angioedema, urticaria. Frequency not known: photosensitivity reaction.

Musculoskeletal and connective tissue disorders, general disorders. Uncommon: osteopenia, osteoporosis.

Frequency not known: rhabdomyolysis.

Renal and urinary disorders. Uncommon: urinary retention.

Injury, poisoning and procedural complications. Frequency not known: falls due to adverse reactions leading to impaired body balance.

Blood and lymphatic system disorders. Uncommon: leukopenia, neutropenia (see section "Special precautions").

Rare: agranulocytosis (see section "Special precautions").

Vascular disorders. Common: arterial hypotension.

Uncommon: increased blood pressure.

Rare: cases of venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis have been reported during treatment with antipsychotic drugs (see section "Special precautions").

Pregnancy, puerperium and perinatal disorders. Frequency not known: withdrawal syndrome in newborns (see section "Use during pregnancy or breastfeeding").

Reporting of suspected adverse reactions

Reporting of adverse reactions after marketing authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

In case of adverse reactions or questions regarding the safety and efficacy of the medicinal product, please contact the Pharmacovigilance Department of LLC "ASINO UKRAINE" at: 8 Vatslava Havela Boulevard, Kyiv, 03124, Tel/Fax: +38 044 281 2333.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

10 tablets per blister; 1, 3, or 6 blisters per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC "Pharma Start", Ukraine.

Manufacturer's address and location of business activity.

8 Vatslava Havela Boulevard, Kyiv, 03124, Ukraine.