Instructions for use Soleron 100 tablets 100 mg blister No. 30
Composition
active ingredient: amisulpride;
1 tablet contains amisulpride 100 mg or 200 mg;
Excipients: lactose monohydrate, microcrystalline cellulose, hydroxypropylmethylcellulose, croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
Round tablets, with a biconvex surface, white or almost white in color, with a score.
Pharmacotherapeutic group
Antipsychotic drugs.
ATX code N05A L05.
Pharmacological properties
Pharmacodynamics. Amisulpride is an antipsychotic drug belonging to the class of substituted benzamides. Its pharmacodynamic properties are characterized by selective and predominant affinity for D2 and D3 receptors of the limbic system. Amisulpride has no affinity for serotonin receptors and other neuroreceptors such as histamine receptors, cholinergic and adrenergic receptors.
At high doses, it blocks predominantly dopaminergic neurons located in the mesolimbic structures rather than in the striatal system. This specific affinity explains the superiority of amisulpride's antipsychotic effects over its extrapyramidal effects.
At low doses, it predominantly blocks presynaptic D2/D3 receptors, which explains its effect on the negative symptoms of schizophrenia.
It is known that in a study comparing it with haloperidol, amisulpride was significantly more effective than haloperidol in alleviating secondary negative symptoms in patients with acute schizophrenia.
Pharmacokinetics: After administration of amisulpride, two absorption peaks are observed: one is reached quickly, one hour after the dose, and the second - after 3-4 hours. Plasma concentrations are 39±3 and 54±4 ng/ml, respectively, after a dose of 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: two inactive metabolites have been identified, accounting for approximately 4% of the total amount of the drug administered.
Amisulpride does not accumulate and its pharmacokinetics remain unchanged after repeated doses. The elimination half-life of amisulpride is approximately 12 hours after oral administration.
Amisulpride is excreted unchanged in the urine. Renal clearance is approximately 330 ml/min.
A carbohydrate-rich meal significantly reduces the AUC (area under the concentration/time curve), Tmax (time to reach maximum concentration) and Cmax (maximum concentration) of amisulpride in the blood. Similar changes in these parameters were not observed after the consumption of a fatty meal. The effect of these changes during treatment with amisulpride is unknown.
Hepatic impairment: Since amisulpride is only slightly metabolized, there is no need to reduce the dose in patients with hepatic impairment.
Renal insufficiency. In patients with renal insufficiency, the half-life does not change, while systemic clearance is reduced by 2.5-3 times.
The AUC of amisulpride increases twofold in mild renal failure, and almost 10-fold in moderate renal failure.
Practical experience is limited and there are no data on doses of 50 mg.
Amisulpride is poorly dialyzable.
Elderly: Available pharmacokinetic data in patients aged 65 years and older indicate that after a single 50 mg dose, Cmax, T1/2 and AUC increase by 10-30%. There are no data on repeated doses.
Indication
Schizophrenia.
Contraindication
- Hypersensitivity to the active substance or any component of the drug.
- Known or suspected pheochromocytoma, as serious cases of arterial hypertension have been described in patients with pheochromocytoma who have been treated with antidopaminergic drugs, including some benzamides.
- Diagnosed or suspected prolactin-dependent tumors (e.g. prolactin-secreting pituitary adenoma and breast cancer).
- Use in combination with levodopa (see section "Interaction with other medicinal products and other types of interactions").
- Combination with medicinal products that may cause torsades de pointes (see section "Interaction with other medicinal products and other types of interactions").
- In combination with mecitalopram, citalopram, escitalopram, non-antiparkinsonian dopamine agonists (cabergoline, quinagolide).
Interaction with other medicinal products and other types of interactions
Contraindicated combinations.
Drugs that can cause torsades de pointes:
– class Ia antiarrhythmics such as quinidine, disopyramide;
– class III antiarrhythmics such as amiodarone, solatol;
– other drugs such as bepridil, cisapride, sultopride, thioridazine, methadone, intravenous erythromycin, intravenous vincomycin, halofantrine, pentamidine, sparfloxacin.
Combinations that are not recommended.
Amisulpride may enhance the effects of alcohol on the central nervous system.
Drugs that increase the risk of torsades de pointes or may prolong the QT interval:
- drugs that induce bradycardia, such as beta-blockers, calcium channel blockers that induce bradycardia, such as diltiazem and verapamil, clonidine, guaifenesin; digitalis preparations;
- drugs that induce hypokalemia: hypokalemic diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, tetracosactides. Hypokalemia must be corrected;
- neuroleptics such as pimozide, haloperidol; imipramine antidepressants; lithium.
Combinations to consider.
Central nervous system depressants, including narcotics, analgesics, sedative antihistamines, H1-receptor blockers, barbiturates, benzodiazepines and other anxiolytics, clonidine and derivatives.
Antihypertensive drugs and other antihypertensive agents.
Application features
Neuroleptic malignant syndrome. As with other neuroleptics, amisulpride may cause the development of neuroleptic malignant syndrome (which can be fatal), characterized by hyperthermia, muscle rigidity, peripheral nervous system dysfunction, impaired consciousness, and elevated serum creatine phosphokinase. If hyperthermia develops, especially at high doses, all antipsychotics, including amisulpride, should be discontinued.
QT prolongation: Amisulpride may cause a dose-dependent prolongation of the QT interval on the ECG, which increases the risk of dangerous ventricular arrhythmias such as ventricular fibrillation-flutter. The risk of developing serious ventricular arrhythmias is increased in bradycardia, hypokalemia, in the case of congenital or acquired prolonged QT interval (combination with drugs that prolong the QT interval).
If the clinical situation allows, before using the drug, it is recommended to make sure that there are no factors that may contribute to the development of this rhythm disorder: bradycardia less than 55 beats/min; electrolyte imbalance, in particular hypokalemia; congenital prolonged QT interval; simultaneous use of drugs that can cause severe bradycardia (< 55 beats/min), hypokalemia, decreased cardiac conduction or prolongation of the QT interval (see sections "Contraindications" and "Interaction with other medicinal products and other types of interactions").
Patients who require long-term treatment with neuroleptics should have an ECG performed before starting treatment.
Stroke. There is evidence that elderly patients with dementia treated with some atypical antipsychotics have an increased risk of developing stroke. The mechanism underlying this increased risk is unknown. An increased risk associated with other antipsychotics and other patient groups cannot be excluded. This medicinal product should be used with caution in patients with risk factors for stroke.
Elderly patients with dementia. Elderly patients with dementia-related psychosis who are taking antipsychotics are at increased risk of death. Studies in patients who were predominantly taking atypical antipsychotics have shown a 1.6- to 1.7-fold increased risk of death compared with placebo. Although the causes of death in clinical trials with atypical antipsychotics varied, most deaths were due to either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) causes. Available evidence suggests that conventional antipsychotics may increase mortality, as do atypical antipsychotics. The role of antipsychotics and patient characteristics in increasing mortality remains unclear.
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients taking antipsychotics often have acquired risk factors for VTE, possible risk factors for VTE should be identified before initiating or during treatment with Soleron and preventive measures should be taken.
Breast cancer: Amisulpride may increase prolactin levels. Therefore, amisulpride should be prescribed with caution to patients with a personal or family history of breast cancer, and close monitoring is necessary during therapy with this drug.
Hyperglycemia.
Cases of hyperglycemia or impaired glucose tolerance and development or exacerbation of diabetes mellitus have been reported in patients treated with some antipsychotics, including amisulpride (see section 4.8).
Convulsions: Amisulpride may lower the seizure threshold, therefore special monitoring is necessary for patients with a history of seizures who are taking Soleron.
Special patient groups.
Since amisulpride is excreted by the kidneys, in cases of impaired renal function, the dose should be reduced or alternative treatment should be considered (see section 4.2). There are no data in patients with severe renal impairment.
In elderly patients, Soleron, like other neuroleptics, should be used with special caution due to the possible risk of developing arterial hypotension or sedation. For such patients, a dose reduction of the drug may be necessary due to impaired renal function.
It is necessary to use Soleron with extreme caution in Parkinson's disease, as it may lead to a worsening of the disease. Amisulpride should be used only if treatment with neuroleptics cannot be avoided.
Withdrawal syndrome: Cases of withdrawal syndrome have been described after abrupt discontinuation of high doses of antipsychotics. Involuntary movement disorders (such as akathisia, dystonia, dyskinesia) have been reported. Therefore, gradual discontinuation of amisulpride is advisable.
Other: Leukopenia, neutropenia, and agranulocytosis have been reported with the use of antipsychotics, including amisulpride.
Fever or infection of unknown etiology may indicate leukopenia (see section "Adverse reactions") and require immediate haematological examination.
It is not recommended to use this medicine in combination with alcohol, dopaminergic antiparkinsonian agents, antiparasitic agents that can provoke torsades de pointes; with methadone, levodopa, other neuroleptics or drugs that can provoke torsades de pointes (see section "Interaction with other medicinal products and other types of interactions").
The drug contains lactose, therefore it is not recommended for use in patients with lactase deficiency, galactosemia or glucose or galactose malabsorption syndrome.
Use during pregnancy or breastfeeding
Pregnancy: Amisulpride has not been shown to have reproductive toxicity in animal studies. A decrease in fertility was observed, which is related to the pharmacological effects of the drug (prolactin-mediated effect). No teratogenic effects of amisulpride have been observed.
Clinical data on the use of amisulpride during pregnancy are limited. Accordingly, its safety during pregnancy has not been established, and therefore the use of the drug is not recommended unless the benefit outweighs the risk. If amisulpride is used during pregnancy, adverse effects of amisulpride may occur in the newborn. When used in the third trimester of pregnancy, adverse reactions such as extrapyramidal symptoms and/or withdrawal syndrome may occur in the newborn, with varying degrees of severity and duration after birth. Adverse reactions such as agitation, hypertonia, hypotension, tremor, drowsiness, respiratory distress syndrome or difficulty feeding have been reported. Therefore, careful monitoring of the condition of the newborn is necessary.
Breastfeeding. It is not known whether amisulpride passes into breast milk, therefore breastfeeding is contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients, especially those who drive or operate machinery, should be warned about the risk of drowsiness associated with the use of this medicinal product (see section "Adverse reactions").
Method of administration and doses
The drug is used internally.
If the daily dose does not exceed 400 mg, Soleron should be taken once a day. Doses greater than 400 mg should be divided into 2 doses per day.
For acute psychotic episodes, the recommended starting dose is 400 –
800 mg, maximum daily dose – no more than 1200 mg. The safety of doses above 1200 mg/day has not been sufficiently studied. Therefore, such doses should not be used. The maintenance dose or dose adjustment should be established individually, according to the patient's response. Maintenance treatment is carried out with the minimum effective dose, which is established individually.
For patients with predominantly negative symptoms, it is recommended to prescribe the drug in a dose of 50 mg (1/2 tablet of 100 mg) to 300 mg per day. The dose is selected individually. The optimal dose is approximately 100 mg per day.
Elderly patients.
The safety of amisulpride in elderly patients has been evaluated in a limited number of patients. This drug should be used with particular caution in this subgroup of patients due to the risk of hypotension and sedative effects. In patients with renal insufficiency, a dose reduction may also be necessary (see section 4.4).
Due to insufficient data regarding the use of amisulpride in patients with severe renal insufficiency (creatinine clearance < 10 ml/min), careful monitoring of the condition of such patients is recommended.
Hepatic impairment. Since the drug is poorly metabolized in the body, a dose reduction is not required in cases of hepatic impairment.
Children.
The safety and efficacy of amisulpride in children aged 15 years and older have not been established; data on the use of amisulpride in adolescents with schizophrenia are limited. Therefore, the use of amisulpride in children aged 15 years and older is not recommended and is contraindicated in children under 15 years of age.
Overdose
To date, there is limited data on acute overdose of amisulpride. The signs and symptoms reported are mainly the result of increased pharmacological activity, clinically manifested by dizziness, drowsiness, sedation, hypotension, extrapyramidal symptoms, coma. Fatalities have been reported with amisulpride, mainly when used concomitantly with other psychotropic drugs.
The specific antidote to amisulpride is unknown.
In case of acute overdose, it is necessary to determine whether another drug was used simultaneously and take appropriate measures: supportive therapy, monitoring of vital body functions, especially monitoring of cardiac activity (danger of prolongation of the QT interval) until the patient's condition is completely normalized. If pronounced extrapyramidal symptoms appear, anticholinergic drugs are prescribed. The use of hemodialysis is not effective because amisulpride is poorly dialyzed.
Adverse reactions
Adverse reactions are classified by frequency according to the following scale: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), frequency unknown (cannot be estimated from the available data).
In some cases, it can be difficult to distinguish between adverse reactions and symptoms of the underlying disease.
From the nervous system: very often - extrapyramidal symptoms (including tremor, rigidity, hypertonicity, hypersalivation, akathisia, hypokinesia, dyskinesia). The intensity of these symptoms is usually moderate, they are partially reversible without drug withdrawal when prescribing anticholinergic antiparkinsonian therapy. The frequency of development of extrapyramidal symptoms, depending on the dose of the drug, is very low in patients taking the drug at a dose of 50-300 mg/day to eliminate predominantly negative symptoms; often - daytime drowsiness; acute dystonia (spastic torticollis, oculogyric crisis, trismus), which does not require drug withdrawal and resolves with the use of anticholinergic antiparkinsonian drugs; uncommon – tardive dyskinesia, characterized by involuntary movements mainly of the tongue and/or facial muscles, usually develops with prolonged use of the drug (anticholinergic antiparkinsonian drugs are ineffective in this case, they may cause an increase in symptoms); convulsions; frequency unknown – neuroleptic malignant syndrome, sometimes fatal.
Mental disorders: often - insomnia, anxiety, agitation, frigidity; frequency unknown - confusion.
Endocrine disorders: often - reversible increase in serum prolactin levels (resulting after discontinuation of the drug), which may cause galactorrhea, amenorrhea, gynecomastia, breast swelling, and erectile dysfunction.
Metabolic disorders: often - weight gain; infrequently - hyperglycemia; frequency unknown - hypertriglyceridemia and hypercholesterolemia.
On the part of the digestive tract: often - constipation, nausea, vomiting, dry mouth.
Cardiovascular system: often - arterial hypotension; infrequently - bradycardia; frequency unknown - prolongation of the QT interval on the ECG; ventricular arrhythmia of the atrial fibrillation-flutter type and ventricular tachycardia, which can lead to ventricular fibrillation and cardiac arrest; sudden death (see section "Special instructions").
Venous thromboembolism, including pulmonary embolism (sometimes fatal) and deep vein thrombosis, have been observed with the use of antipsychotics.
On the part of the hepatobiliary system: infrequently - increased activity of liver enzymes, mainly transaminases.
On the part of the immune system: infrequently - allergic reactions.
Skin and subcutaneous tissue disorders: frequency unknown - urticaria, angioedema.
Blood and lymphatic system disorders: frequency unknown - leukopenia, neutropenia, agranulocytosis.
Other: withdrawal syndrome in newborns.
Expiration date
3 years.
Storage conditions
Store in the original packaging, out of the reach of children, at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister; 1, 3 or 6 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Pharma Start LLC, Ukraine.
Location of the manufacturer and its business address
Ukraine, 03124, Kyiv, I. Lepse Blvd., 8.
