Instructions for use Soleron tablets 100 mg No. 60
Composition
active ingredient: amisulpride;
1 tablet contains amisulpride 100 mg or 200 mg;
Excipients: lactose monohydrate; microcrystalline cellulose; hydroxypropylmethylcellulose; croscarmellose sodium; colloidal anhydrous silica; 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 rapidly, 1 hour after dosing, and the second is reached 3-4 hours later. Plasma concentrations are 39±3 and 54±4 ng/ml, respectively, after a 50 mg dose.
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 is unchanged, 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 phaeochromocytoma, as serious cases of hypertension have been reported in patients with phaeochromocytoma who have been treated with antidopaminergic drugs, including some benzamides.
- Children under 15 years of age (due to lack of clinical data).
- Breastfeeding.
- 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 mecitazine, citalopram, domperidone, hydroxyzine, escitalopram, non-antiparkinsonian dopamine agonists (cabergoline, quinagolide).
Interaction with other medicinal products and other types of interactions
Sedatives. It should be noted that many drugs or substances can cause additive central nervous system (CNS) depressant effects and contribute to decreased alertness. These include morphine derivatives (analgesics, antitussives and substitution treatments), 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.
Drugs that can cause torsades de pointes. This serious arrhythmia can be caused by a number of drugs, such as antiarrhythmics and other drugs. Predisposing factors include hypokalemia (see section “Potassium-lowering drugs”), bradycardia (see section “Heart rate-slowing drugs”), or pre-existing congenital or acquired QT prolongation.
This is particularly true for class IA and III antiarrhythmics and some neuroleptics. This effect is also induced by other compounds that do not belong to these classes.
For dolasetron, erythromycin, spiramycin and vincamine, this interaction only applies to dosage forms that should be administered intravenously.
In general, the use of a drug that causes torsades de pointes with another drug that has the same effect is contraindicated.
However, some of these drugs are exceptions, as their use cannot be avoided and therefore they are simply not recommended for use in combination with drugs that can induce torsades de pointes. This applies to methadone, antiparasitic drugs (halofantrine, lumefantrine, pentamidine) and neuroleptics.
However, these exceptions do not include citalopram, escitalopram, domperidone, and hydroxyzine, and therefore their use with all drugs that can induce torsades de pointes is contraindicated.
Contraindicated combinations.
Dopamine agonists, except antiparkinsonian agonists (cabergoline, quinagolide, rotigotine). Mutual antagonism of the effects of dopamine agonists and neuroleptics.
Citalopram, escitalopram, domperidone, hydroxyzine. Increased risk of ventricular arrhythmias, especially torsades de pointes.
Mechitazine: Increased risk of ventricular arrhythmias, especially torsades de pointes.
Combinations that are not recommended (see section "Special warnings and precautions for use").
Antiparasitic drugs that can cause torsades de pointes (chloroquine, halofantrine, lumefantrine, pentamidine). Increased risk of ventricular arrhythmias, including torsades de pointes. If possible, treatment with one of the two drugs should be discontinued. If this combination cannot be avoided, pre-treatment QT monitoring and ECG monitoring are recommended.
Dopaminergic antiparkinsonian drugs (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, rasagiline, ropinirole, rotigotine, selegiline, tolcapone). Mutual antagonism of the effects of dopamine agonists and neuroleptics. Dopamine agonists can provoke or exacerbate psychotic disorders. When the use of a neuroleptic is necessary for a patient suffering from Parkinson's disease and taking dopamine agonists, it is necessary to gradually reduce the dose of dopamine agonists, and then discontinue the drug (abrupt withdrawal of dopaminergic drugs threatens the development of neuroleptic malignant syndrome).
Other drugs 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 drugs such as arsenic compounds, bepridil, cisapride, diphemanil, dolasetron intravenously, domperidone, erythromycin intravenously, levofloxacin, mehitazine, mizolastine, prucalopride, vincamine intravenously, moxifloxacin, sparfloxacin, spiramycin intravenously, thioridazine, vandetanib, toremifene. Increased risk of ventricular arrhythmias, including torsades de pointes.
Other neuroleptics that can induce torsades de pointes (chlorpromazine, cyamemazine, droperidol, flupentixol, fluphenazine, haloperidol, levomepromazine, pimozide, pipamperon, pipotiazine, sertindole, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, including torsades de pointes.
Alcohol consumption. Alcohol enhances the sedative effect of neuroleptics. Amisulpride may enhance the effects of alcohol on the CNS. Reduced alertness may make driving and operating machinery dangerous. Alcoholic beverages and medications containing alcohol should be avoided.
Levodopa. Mutual antagonism of the effects of levodopa and neuroleptics. Patients with Parkinson's disease should use the minimum effective doses of each of these drugs.
Methadone: Increased risk of ventricular arrhythmias, including torsades de pointes.
Sodium oxybutyrate. Increased central nervous system depression. Reduced attention may lead to danger when driving vehicles and operating other mechanisms.
Combinations requiring precautions.
Azithromycin, clarithromycin, ciprofloxacin, levofloxacin, norfloxacin, roxithromycin. Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is necessary when these drugs are used concomitantly.
Beta-blockers in patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol). Increased risk of ventricular arrhythmias, especially torsades de pointes. In addition, there is a vasodilatory effect and a risk of arterial hypotension, especially orthostatic (additive effect). Clinical and ECG monitoring is necessary.
Drugs that slow the heart rate (especially class IA antiarrhythmics, beta-blockers, some class III antiarrhythmics, some calcium channel blockers, digitalis, pilocarpine, anticholinesterase drugs). Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is necessary.
Drugs that lower potassium levels (potassium-sparing diuretics, alone or in combination, stimulant laxatives, glucocorticoids, tetracosactides 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, electrolyte and ECG monitoring should be performed.
Lithium: Risk of neuropsychiatric signs suggestive of neuroleptic malignant syndrome or lithium toxicity. Regular clinical and laboratory monitoring is indicated, especially at the beginning of concomitant use.
Ondansetron: Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and electrocardiographic monitoring is required during concomitant use of this drug.
Roxithromycin: Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is necessary when these drugs are used concomitantly.
Combinations to consider.
Other sedatives. Increases CNS depression. Impaired ability to concentrate may make driving and operating machinery dangerous.
Antihypertensives: Increased risk of hypotension, particularly postural hypotension.
Nitrate derivatives and related substances: Increased risk of arterial hypotension, particularly postural hypotension.
Orlistat. Risk of reduced therapeutic effect with concomitant use of orlistat.
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 ((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.
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, the majority of 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 antipsychotic drugs 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).
Clinical and laboratory monitoring should be performed in accordance with current guidelines in patients receiving treatment with Soleron. Particular attention should be paid to patients with diabetes mellitus or with risk factors for the development of diabetes mellitus. If hyperglycemia associated with the use of the drug is detected, the drug should be discontinued.
Convulsions: Amisulpride may lower the seizure threshold, so special attention should be paid to 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. The development of withdrawal symptoms, including nausea, vomiting and insomnia, has been described after abrupt discontinuation of antipsychotics used in high doses. The development of involuntary movement disorders (such as akathisia, dystonia, dyskinesia) has been reported. In this regard, gradual withdrawal of amisulpride is advisable.
Hyperprolactinemia: Amisulpride may increase prolactin levels (see section 4.8). Patients with hyperprolactinemia and/or potentially prolactin-dependent tumors should be closely monitored during treatment with amisulpride (see section 4.3).
Other: Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics, including amisulpride. Fever or unexplained infection may indicate leukopenia (see section 4.8) and require immediate haematological evaluation.
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.
The drug contains 30 or 60 mg of croscarmellose sodium (depending on the dosage of the drug Soleron 100 or Soleron 200). This should be taken into account when calculating the daily sodium intake for patients on a controlled sodium diet.
Use during pregnancy or breastfeeding
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 newborns, with varying degrees of severity and duration after birth. Adverse reactions such as agitation, hypertonia, hypotension, tremor, drowsiness, respiratory distress syndrome or difficulty in 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 to be 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.
In acute psychotic episodes, the recommended initial dose is 400–800 mg, the maximum daily dose is not 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 should be carried out with the minimum effective dose, which is established by the doctor 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 should be 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 required (see section 4.4).
Renal impairment. Since amisulpride is excreted by the kidneys, in cases of renal impairment, the daily dose should be reduced by half for patients with creatinine clearance of 30-60 ml/min, and by a third for patients with creatinine clearance of 10-30 ml/min.
Due to insufficient data regarding the use of amisulpride in patients with severe renal insufficiency (creatinine clearance
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
There is limited data on acute overdose of amisulpride. The reported signs and symptoms 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, since amisulpride is poorly dialyzed.
Adverse reactions
Adverse reactions are classified by frequency according to the following scale: very common (≥ 1/10), common (≥ 1/100,000), very rare (
It is known that data are derived from clinical trials: The following adverse reactions have been observed in controlled clinical trials. In some cases, it may be difficult to distinguish between adverse reactions and symptoms of the underlying disease.
Nervous system disorders: Very common: extrapyramidal symptoms (tremor, rigidity, hypertonia, increased salivation, akathisia, hypokinesia, dyskinesia). In most cases, they are mild at maintenance doses and partially reversible without discontinuation of amisulpride when anticholinergic antiparkinsonian agents are prescribed.
Common: acute dystonia (spastic torticollis, oculogyric crisis, trismus). It is reversible without discontinuation of amisulpride when an anticholinergic antiparkinsonian agent is prescribed. Drowsiness.
Uncommon: Tardive dyskinesia, characterised by involuntary movements of the tongue and/or facial muscles, has been reported, usually after long-term use. Anticholinergic antiparkinsonian agents are ineffective or may exacerbate symptoms. Convulsions.
Psychiatric disorders: Common: insomnia, anxiety, agitation, frigidity.
Gastrointestinal: Common: constipation, nausea, vomiting, dry mouth.
Endocrine disorders: Common: Increased plasma prolactin levels, reversible upon discontinuation of the drug. This may cause the following clinical symptoms: galactorrhea, amenorrhea, gynecomastia, breast pain, erectile dysfunction.
Metabolism and nutrition disorders: Uncommon: hyperglycemia (see section "Special warnings and precautions for use").
Cardiovascular system: Common: hypotension. Uncommon: bradycardia.
Investigations: Common: weight gain. Uncommon: increased liver enzymes, mainly transaminases, have been reported.
Immune system disorders: Uncommon: allergic reactions.
Post-marketing data: The following adverse reactions have been reported from spontaneous reports.
Nervous system disorders: Frequency not known: neuroleptic malignant syndrome, sometimes fatal (see section 4.4).
Cardiac system: Frequency unknown: QT prolongation; ventricular arrhythmias such as torsades de pointes and ventricular tachycardia, which can lead to ventricular fibrillation and cardiac arrest; sudden death (see section "Special warnings and precautions for use").
Blood and lymphatic system disorders: Frequency not known: leukopenia, neutropenia and agranulocytosis (see section 4.4).
Metabolism and nutrition disorders: Frequency unknown: hypertriglyceridemia and hypercholesterolemia.
Psychiatric disorders: Frequency unknown: confusion.
Vascular disorders: Frequency unknown: Cases of venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis have been reported with antipsychotic drugs (see section 4.4).
Skin and subcutaneous tissue disorders: Frequency unknown: angioedema, urticaria.
Pathological conditions during pregnancy, in the puerperium and perinatal periods. Frequency unknown: withdrawal syndrome in newborns (see section "Use during pregnancy or lactation").
Expiration date
3 years.
Storage conditions
Store out of the reach of children, in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 tablets in a blister; 1 or 3 or 6 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
Pharma Start LLC, Ukraine.
Address
Ukraine, 03124, Kyiv, Vaclav Havel Boulevard, 8.
In case of side effects and questions regarding the safety of the drug, please contact ASINO UKRAINE LLC at the address: Vaclav Havel Boulevard, 8, Kyiv, 03124
phone/fax: +38 044 281 2333
