Instructions for Solex tablets 100 mg blister No. 30
Composition
active ingredient: amisulpride;
1 tablet contains amisulpride 100 mg or 200 mg;
Excipients: lactose monohydrate; microcrystalline cellulose; methylcellulose; sodium starch glycolate (type A); magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
- 100 mg tablets: white or almost white, round, flat tablets with a diameter of approximately 8.0 mm, with a score line on one side and embossing A/100 on the other side;
- 200 mg tablets: white or almost white, round, flat tablets with a diameter of approximately 11.0 mm, with a score line on one side and embossed A/200 on the other side.
Pharmacotherapeutic group
Antipsychotics. 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.
In high-dose animal studies, amisulpride preferentially blocks dopaminergic neurons in the mesolimbic system compared to those in the striatal system. This specific affinity explains the superiority of amisulpride's antipsychotic effects over its extrapyramidal effects.
At low doses, amisulpride blocks predominantly presynaptic dopaminergic D2 and D3 receptors, which explains its effect on negative symptoms.
Pharmacokinetics
In humans, amisulpride shows two absorption maxima: the first occurs rapidly, 1 hour after dosing, and the second occurs 3-4 hours later.
The corresponding plasma concentrations after a 50 mg dose are 39 ± 3 and 54 ± 4 ng/ml.
The volume of distribution is 5.8 l/kg, plasma protein binding is low (16%), protein-bound interactions with other drugs are unlikely. Absolute bioavailability is 48%.
Amisulpride is poorly metabolized: two inactive metabolites have been identified, accounting for about 4% of the total amount of the drug administered.
Amisulpride does not accumulate in the body, and its pharmacokinetics remain unchanged after repeated doses.
The half-life after an oral dose is approximately 12 hours.
Amisulpride is excreted unchanged in the urine.
Renal clearance is approximately 330 ml/min.
A carbohydrate-rich meal significantly reduces the AUC, Tmax, and Cmax of amisulpride, while no changes are observed after a fatty meal. The effect of these changes during treatment with amisulpride is unknown.
Liver failure.
Since amisulpride is poorly metabolized, there is no need to reduce the dose for patients with hepatic insufficiency.
Kidney failure.
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, however, is limited and there are no data on doses exceeding 50 mg.
Amisulpride is dialyzed very poorly.
Elderly patients.
Available pharmacokinetic data in patients aged 65 years and older indicate that after a single dose of 50 mg Cmax, T1/2 and AUC increase by 10-30%. Data on repeated doses are not available.
Indication
Treatment of schizophrenia.
Contraindication
- Hypersensitivity to the active substance or to any other component of the medicinal product.
- It is advisable to refrain from prescribing this medicinal product to patients with diagnosed or suspected pheochromocytoma who have taken antidopaminergic drugs, including some benzamides.
- Known or suspected prolactin-dependent tumors, such as 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").
Interaction with other medicinal products and other types of interactions
Sedatives.
It is important to note that many drugs can have an additive CNS depressant effect and contribute to decreased attention. These include morphine derivatives (analgesics, antitussives and substitution therapies), 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 is especially true for class Ia and III antiarrhythmics, as well as some neuroleptics.
As for erythromycin, spiramycin and vincamine, this interaction only applies to intravenous dosage forms.
The simultaneous use of two torsadogenic drugs is contraindicated.
The exception to this rule is methadone and some subclasses:
- antiparasitic drugs (halofantrine, lumefantrine, pentamidine) are not recommended only in combination with other torsadogenic drugs;
- neuroleptics prone to provoking torsades de pointes are also not recommended, but are not contraindicated in combination with other torsadogenic drugs.
Contraindicated combinations (see section "Contraindications").
Levodopa. Mutual antagonism of effects between dopamine agonists and neuroleptics.
Not recommended combinations (see section "Special instructions").
- Antiparasitic drugs that can cause torsades de pointes (halofantrine, lumefantrine, pentamidine).
One of the two treatments should be discontinued if possible.
Increased risk of ventricular arrhythmias, including torsades de pointes.
If this combination cannot be avoided, QT should be checked before treatment and ECG monitoring should be performed.
- Dopaminergic antiparkinsonian agents (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline).
Mutual antagonism of effects between dopamine agonists and neuroleptics.
Dopamine agonists may precipitate or exacerbate psychotic disorders. When neuroleptic use is necessary in a patient with Parkinson's disease who is taking dopamine agonists, the dopamine agonists should be gradually reduced and then discontinued (abrupt withdrawal of dopaminergic compounds carries the risk of neuroleptic malignant syndrome).
- Other drugs that may induce torsades de pointes: class Ia (quinidine, hydroquinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic drugs and other drugs such as bepridil, cisapride, diphemanil, intravenous erythromycin, mizolastine, intravenous vincamine, moxifloxacin, intravenous spiramycin.
Increased risk of ventricular arrhythmias, including torsades de pointes.
- Other neuroleptics capable of causing torsades de pointes (amisulpride, chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, pimozide, pipotiazine, sertindole, sulpiride, sultopride, tiapride, veralipride).
Increased risk of ventricular arrhythmias, including torsades de pointes.
- Alcohol consumption.
Alcohol enhances the sedative effect of neuroleptics.
Reduced attention can make driving and operating other machinery dangerous.
It is necessary to avoid drinking alcoholic beverages and taking medications containing alcohol.
- Methadone.
Increased risk of ventricular arrhythmia, particularly torsades de pointes.
Combinations requiring precautions.
- β-blockers for patients with heart failure (bisoprolol, carvedilol, metoprolol, nebivolol).
Increased risk of ventricular arrhythmias, including torsades de pointes. Clinical and ECG monitoring is required.
- Drugs that cause bradycardia (including class Ia antiarrhythmics, β-blockers, some class III antiarrhythmics, some calcium channel blockers, digitalis preparations, pilocarpine, anticholinesterase drugs).
Increased risk of ventricular arrhythmias, including torsades de pointes.
Clinical observation and ECG monitoring are necessary.
- Potassium-depleting agents (potassium-sparing diuretics, including combinations, 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.
Combinations to consider.
- Antihypertensive drugs.
Increased risk of arterial hypotension, particularly postural hypotension.
- β-blockers (except esmolol, sotalol and β-blockers used in heart failure).
Vasodilator effect and risk of arterial hypotension, in particular postural hypotension (additive effect).
- Nitrate derivatives and related compounds.
Increased level of arterial hypotension, particularly postural hypotension.
Application features
Special warnings.
Neuroleptic malignant syndrome.
As with other neuroleptics, neuroleptic malignant syndrome, which can be fatal, is characterized by hyperthermia, muscle rigidity, peripheral nervous system dysfunction, impaired consciousness, and increased CPK levels. If hyperthermia develops, especially when using high doses, all antipsychotic drugs should be discontinued.
QT interval prolongation.
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, such as, for example:
- bradycardia less than 55 beats/min;
- electrolyte imbalance, in particular hypokalemia;
- congenital prolonged QT interval;
- use of drugs that can cause severe bradycardia (<55 beats/min), hypokalemia, decreased cardiac conduction or prolongation of the QT interval (see section "Contraindications").
Patients who require long-term treatment with neuroleptics should have an ECG performed before starting treatment.
Cerebral stroke.
In randomized, placebo-controlled clinical trials in elderly patients with dementia treated with some atypical antipsychotics, an increased risk of stroke was observed compared to placebo.
The mechanism underlying this increased risk is unknown. An increased risk associated with other antipsychotics and the presence of a risk for other patient populations cannot be excluded. This drug should be used with caution in patients with risk factors for stroke.
Elderly patients with dementia.
The risk of death is increased in elderly patients with dementia-related psychosis who are taking antipsychotics.
An analysis of 17 placebo-controlled clinical trials (average duration – 10 weeks) conducted among patients who took mainly atypical antipsychotics showed that compared to placebo, the risk of death in patients treated with these drugs increased by 1.6-1.7 times.
After treatment lasting an average of 10 weeks, the risk of death was 4.5% in patients receiving treatment, compared with 2.6% in the placebo group.
Although the causes of death during 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.
Epidemiological studies show that traditional antipsychotics may increase mortality, as is the case with atypical antipsychotics.
The respective role of antipsychotics and individual patient characteristics in increasing mortality during epidemiological studies has remained unclear.
Venous thromboembolism.
Cases of venous thromboembolism (VTE), sometimes fatal, have been reported with antipsychotics. Since patients treated with antipsychotics often have acquired risk factors for VTE, possible risk factors for VTE should be identified and preventive measures taken before initiating or during treatment with Solex® (see section 4.8).
Hyperglycemia/metabolic syndrome.
Cases of hyperglycaemia or impaired glucose tolerance and development or exacerbation of diabetes 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 Solex®. Particular attention should be paid to patients with diabetes mellitus or with factors predisposing to diabetes.
Convulsions.
Amisulpride may lower the seizure threshold. Therefore, patients with a history of seizures require careful monitoring during amisulpride therapy.
Special patient groups.
Since amisulpride is eliminated by the kidneys, in patients with renal insufficiency the dose should be reduced or alternative treatment should be considered (see section 4.2). There are no data in patients with severe renal insufficiency (see section 4.2).
As with other antipsychotics, amisulpride should be used with particular caution in elderly patients due to the possible risk of sedation and hypotension.
As with other antidopaminergic agents, caution should be exercised when prescribing amisulpride to patients with Parkinson's disease, as it may worsen the disease. Amisulpride should only be used when neuroleptic treatment cannot be avoided.
Withdrawal syndrome.
Withdrawal symptoms have been described after abrupt discontinuation of high doses of antipsychotics. Involuntary movement disorders (such as akathisia, dystonia and dyskinesia) have been reported with amisulpride. 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 investigation.
Other.
This medicinal product should not be used in combination with alcohol, dopaminergic antiparkinsonian agents, antiparasitic agents that can induce torsades de pointes, methadone, other neuroleptics or drugs that can induce torsades de pointes (see section “Interaction with other medicinal products and other types of interactions”).
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance (galactosemia), the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy
Amisulpride has not shown reproductive toxicity in animal studies. A decrease in fertility was observed, which is associated with the pharmacological effects of the drug (prolactin-mediated effect). No teratogenic effects of amisulpride have been observed.
Clinical data on use during pregnancy are limited. Accordingly, the safety of amisulpride during pregnancy has not been established. Amisulpride is not recommended during pregnancy unless the benefits justify the potential risks.
If the drug is used during pregnancy, the newborn may experience side effects of amisulpride. During the third trimester of pregnancy, there is a risk of adverse reactions such as extrapyramidal syndromes and/or withdrawal syndrome, which may vary in severity and duration after delivery. Adverse reactions such as agitation, hypertonia, hypotension, tremor, drowsiness, respiratory distress syndrome or difficulty in feeding have been reported. In this regard, careful monitoring of the newborn is necessary.
Breast-feeding.
Due to the lack of information on the penetration of amisulpride into breast milk, breastfeeding is contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients, especially those who drive and operate machinery, should be warned about the risk of drowsiness and dizziness associated with the use of this medicinal product (see section "Adverse reactions").
Method of administration and doses
If the daily dose does not exceed 400 mg, the drug should be taken once a day.
Doses above 400 mg should be divided into 2 doses per day.
Acute psychotic episodes.
Treatment can be started with intramuscular administration, which will last for several days, at a maximum dose of 400 mg/day, followed by a transition to oral administration.
Doses of 400 mg/day to 800 mg/day are recommended orally. The maximum oral dose should not exceed 1200 mg/day. The safety of doses above 1200 mg/day has not been extensively studied. Therefore, such doses should not be used.
The maintenance dose or dose adjustment should be individualized according to the patient's response.
In all cases, maintenance therapy should be prescribed individually, at the minimum effective dose.
Mostly negative episodes.
Recommended doses range from 50 mg/day to 300 mg/day. Doses should be adjusted individually. The optimal dose is about 100 mg/day.
Elderly patients.
Amisulpride should be used with particular caution in this patient population due to the risk of hypotension and sedation (see section "Contraindications").
Kidney failure.
Since amisulpride is excreted by the kidneys, in renal failure with creatinine clearance 30-60 ml/min the daily dose should be reduced by half, and in renal failure with creatinine clearance 10-30 ml/min - by a third. Due to insufficient data in patients with severe renal failure (CC < 10 ml/min), close monitoring of such patients is recommended (see section "Contraindications").
Liver dysfunction.
Since the drug is poorly metabolized, dose reduction is not required.
Children.
The efficacy and safety of amisulpride in children from puberty to 18 years of age have not been established; data on the use of amisulpride in children with schizophrenia are limited. For this reason, the use of amisulpride in children from puberty to 18 years of age is not recommended. Amisulpride is contraindicated in children under 15 years of age due to the lack of clinical data.
Overdose.
There is currently limited data on acute overdose of amisulpride. The symptoms reported are mainly the result of increased pharmacological activity, clinically manifested by dizziness, sedation, coma, hypotension and extrapyramidal symptoms.
There have been reports of fatalities when used concomitantly with other psychotropic drugs.
There is no specific antidote for amisulpride. In the event of acute overdose, it should be determined whether another drug has been used concomitantly and appropriate measures should be taken:
- careful monitoring of vital functions;
- monitoring of cardiac activity (risk of QT interval prolongation) until the patient recovers completely;
- in case of severe extrapyramidal symptoms, anticholinergics should be prescribed;
- Since amisulpride is poorly dialyzable, the possibilities of hemodialysis for the removal of this medicinal compound are limited.
Adverse reactions
From the nervous system.
The dose-dependent incidence of extrapyramidal symptoms is very low in patients treated for predominantly negative symptoms with doses of 50-300 mg/day.
Common: Acute dystonia (spastic torticollis, oculogyric crisis, trismus, etc.) is possible. 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 of the drug.
Anticholinergic antiparkinsonian drugs are ineffective or may cause worsening of symptoms.
Convulsions.
From the nervous system.
Insomnia, anxiety, agitation, frigidity.
From the digestive system.
Constipation, nausea, vomiting, dry mouth.
From the endocrine system.
Increased plasma prolactin levels, which are reversible after drug withdrawal. This may cause the following clinical symptoms: galactorrhea, amenorrhea, gynecomastia, breast pain, erectile dysfunction.
From the side of metabolism and nutrition.
Weight gain, hyperglycemia (see section "Special warnings and precautions for use").
From the cardiovascular system.
Arterial hypotension, bradycardia.
Laboratory studies.
Elevated levels of liver enzymes, mainly transaminases, have been reported.
From the immune system.
Allergic reactions.
Post-marketing data
The following adverse reactions have been reported from spontaneous reports.
From the nervous system.
Neuroleptic malignant syndrome.
From the cardiovascular system:
- prolongation of the QT interval;
- ventricular arrhythmias such as torsades de pointes and ventricular tachycardia, which can lead to ventricular fibrillation and cardiac arrest;
- sudden death (see section "Special precautions for use").
Cases of venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis have been reported with the use of antipsychotics (see section 4.4).
From the blood and lymphatic system.
Leukopenia, neutropenia and agranulocytosis (see section "Special warnings and precautions for use").
On the skin and subcutaneous tissue.
Angioedema, urticaria.
Pathological conditions during pregnancy, postpartum and perinatal periods.
Withdrawal syndrome in newborns (see section "Use during pregnancy or breastfeeding").
Expiration date
36 months.
Storage conditions
Store in a dry place, protected from light, in the original packaging, at a temperature of 15-25 ° C. Keep out of the reach of children.
Packaging
No. 30 (10x3): 10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Rivopharm SA.
Location of the manufacturer and address of its place of business
Centro Insema, 6928 Manno, Switzerland.
