Instructions Soleron 200 tablets 200 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. Amisulpride selectively binds with high affinity to the D2/D3 subtypes of dopaminergic receptors. Amisulpride has no affinity for serotonin, histamine, adrenergic and cholinergic receptors.
At high doses, it blocks mainly dopaminergic neurons located in the mesolimbic structures, rather than in the striatal system. This specific affinity explains mainly the antipsychotic action of amisulpride.
At low doses, it predominantly blocks presynaptic D2/D3 receptors, which explains its effect on the negative symptoms of schizophrenia.
In a controlled (with haloperidol) double-blind clinical trial in patients with acute schizophrenia, amisulpride significantly alleviated the severity of secondary negative symptoms of the disease to a significantly greater extent than haloperidol.
Pharmacokinetics: After administration of amisulpride, two absorption peaks are observed: one is reached rapidly, one hour after dosing, and the other between 3 and 4 hours after dosing. 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 in the body: two inactive metabolites have been identified, accounting for approximately 4% of the administered dose. There is no accumulation of amisulpride, 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. After intravenous administration, 50% of the dose is excreted in the urine, with 90% of this amount excreted within the first 24 hours. Renal clearance is approximately 20 l/h or 330 ml/min.
A carbohydrate-rich meal (containing up to 68% liquid) significantly reduces 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 taking a fatty meal.
Due to the fact that amisulpride is poorly metabolized, there is no need to reduce the dose of Soleron for patients with impaired liver function.
The elimination half-life in patients with renal insufficiency is unchanged, but the total clearance is reduced by 2.5-3 times. The AUC of amisulpride increases by twofold in mild renal insufficiency, and by almost tenfold in moderate renal insufficiency. However, practical experience with the drug is limited, and there are no results from the use of doses exceeding 50 mg.
Amisulpride is poorly dialyzable.
Indication
Schizophrenia.
Contraindication
- Hypersensitivity to the active substance or any component of the drug.
- Diagnosed or suspected pheochromocytoma.
- Diagnosed or suspected prolactin-dependent tumors (e.g. pituitary prolactinoma and breast cancer).
- Use in combination with levodopa.
- Children under 15 years of age (due to lack of clinical data).
Interaction with other medicinal products and other types of interactions
Drugs that can cause torsades de pointes.
This serious cardiac arrhythmia can be caused by a number of antiarrhythmic and other drugs. Hypokalemia is a predisposing risk factor, as are bradycardia and congenital or acquired QT prolongation. This is particularly true for class Ia and III antiarrhythmics and some neuroleptics. For erythromycin, spiramycin and vincamine, this interaction only applies to intravenous formulations.
The simultaneous use of two drugs that can cause torsades de pointes is contraindicated. The exceptions are methadone and some subclasses of drugs:
- antiparasitic drugs (halofantrine, lumefantrine, pentamidine) are not recommended only in combination with other drugs that can cause torsades de pointes;
- neuroleptics that can provoke torsades de pointes are also not recommended, but are not contraindicated in combination with other drugs that can cause torsades de pointes.
Contraindicated combinations.
Levodopa. Mutual antagonism of effects between dopamine agonists and neuroleptics.
Not recommended combinations.
Antiparasitic drugs that can cause torsades de pointes (halofantrine, lumefantrine, pentamidine).
If possible, one of the drugs should be discontinued. If this combination cannot be avoided, the QT interval should be determined on the ECG before starting treatment, and treatment should be carried out under ECG control.
Other medications that can cause torsades de pointes:
Class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, ibutilide), some neuroleptics (chlorpromazine, levomepromazine, cyamemazine, sulpiride, sultopride, tiapride, veralipride, pimozide, pipotiazine, sertindole, haloperidol, droperidol) and other drugs such as bepridil, cisapride, diphemanil, intravenous erythromycin, mizolastine, intravenous vincamine, moxifloxacin, intravenous spiramycin - increased risk of developing ventricular arrhythmias, including torsades de pointes.
Alcohol – increases the sedative effect of neuroleptics and reduces alertness. It is necessary to avoid drinking alcohol and taking medications containing alcohol during treatment with Soleron.
Dopaminergic agonists other than levodopa (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline), which are used to treat patients with Parkinson's disease. Dopaminergic agonists and neuroleptics are mutual antagonists. Dopaminergic agonists can cause or exacerbate psychotic disorders. If neuroleptic treatment is necessary for a patient with Parkinson's disease who is taking a dopaminergic drug, the dose of the dopamine agonist should be gradually reduced until completely discontinued (abrupt withdrawal of dopaminergic drugs can lead to the development of neuroleptic malignant syndrome).
Combinations that require careful use.
Beta-blockers in heart failure: bisoprolol, carvedilol, metoprolol, nebivolol. Increased risk of ventricular arrhythmias, including torsades de pointes. Clinical and ECG monitoring is necessary.
Drugs that cause bradycardia (including some calcium channel blockers, beta-blockers other than sotalol; digitalis preparations, pilocarpine, cholinesterase inhibitors) - increase the risk of ventricular arrhythmias, especially torsades de pointes. Clinical and ECG monitoring is necessary.
Drugs that can cause hypokalemia: potassium-sparing diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, tetracosactide - increase the risk of ventricular arrhythmias, especially torsades de pointes. Hypokalemia must be corrected before starting the drug. Monitoring of electrolyte balance, ECG, and patient condition is necessary.
Combinations to consider.
Antihypertensive drugs, nitrate derivatives and similar compounds - increased risk of developing arterial hypotension, in particular postural hypotension.
Beta-blockers (except esmolol, sotalol and beta-blockers used for heart failure) – vasodilator effect, risk of developing arterial hypotension, especially orthostatic (additive effect).
Other drugs that have a depressant effect on the CNS: morphine derivatives (analgesics, antitussives), neuroleptics, barbiturates, benzodiazepines and other anxiolytics (such as meprobamate), hypnotics, antidepressants with sedative effects (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), H1-receptor blockers with sedative effects, centrally acting antihypertensive drugs, baclofen, thalidomide - increased central depression, impaired alertness and reaction speed.
Application features
Neuroleptic malignant syndrome. As with other neuroleptics, treatment with Soleron may cause the development of neuroleptic malignant syndrome (which can be fatal), characterized by hyperthermia, muscle rigidity, peripheral nervous system dysfunction, impaired consciousness, and increased serum creatine phosphokinase levels. If hyperthermia develops, especially at high doses, all antipsychotic drugs, including Soleron, 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 tachyarrhythmias 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, hypokalemia, congenital prolonged QT interval, simultaneous use of drugs that can cause severe bradycardia (<55 beats/min), hypokalemia, decreased cardiac conduction or prolonged QT interval. Patients who require long-term treatment with neuroleptics should have an ECG before starting treatment.
Elderly patients with dementia. Elderly patients with dementia-related psychosis who are taking antipsychotics are at increased risk of death. Studies conducted in patients who were predominantly taking atypical antipsychotics have shown a 1.6- to 1.7-fold increased risk of death compared with placebo. 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.
Hyperglycemia: Cases of hyperglycemia or impaired glucose tolerance, development or exacerbation of diabetes have been reported in patients treated with some atypical antipsychotics, including amisulpride. Clinical monitoring of patients with diabetes mellitus or with risk factors for diabetes should be performed to control blood sugar levels when using Soleron.
Convulsions: Soleron may lower the seizure threshold, so 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 only be used when 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 ataxia, dystonia, dyskinesia) have been reported. Therefore, gradual discontinuation of amisulpride is advisable.
Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotics, including amisulpride. Fever or unexplained infection may indicate abnormal blood cell counts and require immediate haematological evaluation.
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
Amisulpride has not shown reproductive toxicity in animal studies. It has also not been shown to be teratogenic.
Clinical data on the use of amisulpride during pregnancy are limited. Accordingly, its safety during pregnancy has not been established, and therefore its use 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, which may vary in severity and duration. 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.
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
The drug may cause drowsiness, as a result of which the ability to drive vehicles or perform work requiring increased attention may be impaired.
Method of administration and doses
It is used internally by adults and children over 15 years of age.
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 –
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.
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 impairment (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 to 18 years 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 to 18 years is not recommended and is contraindicated in children under 15 years of age.
Overdose
Possible enhancement of the known pharmacological effects of the drug, such as drowsiness, sedation, hypotension, extrapyramidal symptoms, coma. A specific antidote for amisulpride is unknown.
In case of acute overdose, supportive therapy, monitoring of vital functions of the body, especially ECG control, is indicated until the patient's condition is completely normalized. If severe extrapyramidal symptoms appear, anticholinergic drugs are prescribed. The use of hemodialysis is not effective.
Adverse reactions
From the nervous system: often - insomnia, anxiety, agitation, extrapyramidal symptoms (including tremor, rigidity, arterial hypertension, 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 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 mainly negative symptoms; daytime drowsiness; acute dystonia (spastic torticollis, oculogyric crisis, trismus), which does not require drug withdrawal and which 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); seizures; neuroleptic malignant syndrome, sometimes fatal.
Endocrine disorders: often - reversible increase in serum prolactin levels (reversible after drug withdrawal), which may cause galactorrhea, amenorrhea, gynecomastia, breast swelling, erectile dysfunction; frigidity; weight gain.
Metabolic disorders: uncommon – hyperglycemia.
On the part of the digestive tract: often - constipation, nausea, vomiting, dry mouth.
Cardiovascular system: very rarely - arterial hypotension and bradycardia, prolongation of the QT interval on the ECG; ventricular tachyarrhythmia of the torsades de pointes type, which can lead to ventricular fibrillation and cardiac arrest. 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: very rarely - increased activity of liver enzymes, especially transaminases.
On the part of the immune system: very rarely - allergic reactions, including angioedema.
Skin and subcutaneous tissue disorders: urticaria.
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 cardboard packs.
Vacation category
According to the recipe.
Producer
Pharma Start LLC, Ukraine.
Location of the manufacturer and address of its place of business
Ukraine, 03124, Kyiv, I. Lepse Blvd., 8.
