Instructions for use Aktiprol tablets 200 mg blister No. 30
Composition
active ingredient: amisulpride;
1 tablet contains amisulpride 100 mg or 200 mg;
Excipients: lactose monohydrate; sodium starch glycolate (type A); hypromellose 2910 E5; microcrystalline cellulose (PH-101); magnesium stearate.
Dosage form
Pills.
Main physicochemical properties:
100 mg tablets: white round flat tablets with a diameter of 9.5 mm, embossed with MC on one side;
200 mg tablets: white, round, flat tablets with a diameter of 11.5 mm with a score line on one side.
Pharmacotherapeutic group
Psycholeptics. Antipsychotics. Benzamides. Amisulpride. 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 the same neurons 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.
In a controlled, double-blind clinical trial comparing haloperidol with 191 patients with acute schizophrenia, amisulpride was significantly more effective than haloperidol in relieving secondary negative symptoms.
Pharmacokinetics.
In humans, amisulpride shows two absorption peaks: the first occurs rapidly, 1 hour after dosing, and the second occurs 3-4 hours later. Plasma concentrations after a 50 mg dose are 39 ± 3 and 54 ± 4 ng/ml, respectively.
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 approximately 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 oral administration is approximately 12 hours. Amisulpride is excreted unchanged in the urine. 50% of an intravenous dose is excreted in the urine, with 90% of this amount excreted in the first 24 hours. 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.
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 by twofold in mild renal insufficiency, and by almost 10-fold in moderate renal insufficiency. Practical experience is limited and there are no data on doses of 50 mg. Amisulpride is very poorly dialysable.
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.
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 damage. In animal studies, amisulpride affected the growth and intrauterine development of the fetus at doses equivalent to 2000 mg/day and above for a human weighing 50 kg. There is no evidence that amisulpride has any teratogenic potential. No studies of the effects of amisulpride on the behavior of the offspring have been conducted. Carcinogenicity studies have shown that hormone-dependent tumors develop in rodents when the drug is used. These data have no clinical relevance to humans. In animals, a decrease in fertility associated with the pharmacological properties of the drug (prolactin-mediated effects) was observed.
Indication
Schizophrenia.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product listed in the "Composition" section.
Serious episodes of hypertension have been reported in patients with pheochromocytoma who have been treated with antidopaminergic drugs, including some benzamides. Therefore, it is recommended that this drug be avoided in patients with known or suspected pheochromocytoma.
Known or suspected prolactin-dependent tumor, such as pituitary prolactinoma and breast cancer (see sections "Special instructions" and "Adverse reactions").
Use in combination with citalopram, escitalopram, domperidone, hydroxyzine, piperaquine, non-antiparkinsonian dopaminergic drugs (cabergoline, quinagolide) (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Sedatives. It should be noted that many drugs or substances can cause additive CNS depressants 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 antiarrhythmic drugs of classes IA and III, as well as some neuroleptics. This effect is also induced by compounds that do not belong to these classes.
For dolasetron, erythromycin, spiramycin and vincamine, this interaction only applies to the intravenous formulations. In general, the use of a drug that induces 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 (chloroquine, halofantrine, lumefantrine, pentamidine) and neuroleptics. However, these exceptions do not include citalopram, escitalopram, domperidone and hydroxyzine, and their use with any drug that can induce torsades de pointes is contraindicated.
Contraindicated combinations
Dopamine agonists, except antiparkinsonian agonists (cabergoline, quinagolide). Mutual antagonism of the effects of dopamine agonists and neuroleptics.
Citalopram, escitalopram, domperidone, hydroxyzine, piperaquine. Increased risk of ventricular arrhythmias, especially torsades de pointes.
Not recommended combinations
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 with Parkinson's disease who is taking dopamine agonists, the dose of dopamine agonists should be gradually reduced and then the drug should be discontinued (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, diphemanil, dolasetron intravenous, erythromycin intravenous, levofloxacin, mehitazine, mizolastine, prucalopride, vincamine intravenous, moxifloxacin, spiramycin intravenous, 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, sulpiride, sultopride, tiapride, zuclopenthixol). Increased risk of ventricular arrhythmias, including torsades de pointes.
Alcohol (both in alcoholic beverages and in excipients). Alcohol enhances the sedative effect of neuroleptics. Reduced attention can make driving and operating other mechanisms dangerous. It is necessary to avoid drinking alcoholic beverages and taking medications containing alcohol.
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.
Hydroxychloroquine: Increased risk of ventricular arrhythmias, especially torsades de pointes.
Combinations requiring precautions
Anagrelide: Increased risk of ventricular arrhythmias, especially torsades de pointes. Clinical and electrocardiographic monitoring is required during concomitant use of this drug.
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 heart failure (bisoprolol, carvedilol, metoprolol, nebivolol). Increased risk of ventricular arrhythmias, especially torsades de pointes. In addition, there is a vasodilator 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 starting 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.
Combinations to consider
Other sedatives. Increases central nervous system depression. Impaired ability to concentrate may make driving and operating other machinery dangerous.
Orlistat. Risk of reduced therapeutic effect with concomitant use of orlistat.
Application features
Potentially fatal neuroleptic malignant syndrome. As with other neuroleptics, neuroleptic malignant syndrome, which can be fatal and is characterized by hyperthermia, muscle rigidity, autonomic disorders, impaired consciousness, rhabdomyolysis, and elevated creatine phosphokinase levels, may occur. If hyperthermia develops, especially at high doses, all antipsychotic drugs, including amisulpride, should be discontinued. Rhabdomyolysis has also been observed in patients without neuroleptic malignant syndrome.
QT prolongation: Amisulpride may cause a dose-dependent prolongation of the QT interval on the electrocardiogram, which increases the risk of serious ventricular arrhythmias such as torsades de pointes. The risk of serious ventricular arrhythmias is increased in bradycardia, hypokalemia, in the case of congenital or acquired prolonged QT interval (combination with drugs that prolong the QTc interval) (see section "Adverse reactions").
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:
- bradycardia less than 55 beats/min;
- hypokalemia;
- congenital prolonged QT interval;
- use of drugs that can cause severe bradycardia (< 55 beats/min), hypokalemia, decreased cardiac conduction or QT interval prolongation (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. In randomized, placebo-controlled clinical trials in elderly patients with dementia treated with some atypical antipsychotics, the risk of stroke was threefold higher than in patients treated with placebo. The mechanism underlying this increased risk is unknown. An increased risk with other antipsychotics and the presence of a risk in other patient populations cannot be excluded. This drug should be used with caution in patients with risk factors for stroke.
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.
Observational studies suggest that traditional antipsychotics may increase mortality, as do atypical antipsychotics.
The respective role of antipsychotics and patient characteristics in increasing mortality during epidemiological studies has remained unclear.
Venous thromboembolism: Cases of venous thromboembolism (VTE) 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 before initiating or during treatment with Actiprol® and preventive measures should be taken (see section 4.8).
Hyperglycemia/metabolic syndrome: 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).
In accordance with current recommendations, clinical and laboratory monitoring of patients receiving treatment with Actiprol® should be carried out. Particular attention should be paid to patients with diabetes mellitus or with risk factors for its development.
Convulsions: Amisulpride may lower the seizure threshold. Therefore, patients with a history of seizures should be carefully monitored 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 caution in the elderly due to the potential risk of sedation and hypotension. Elderly patients may also require a dose reduction due to renal impairment (see section 4.2).
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, including nausea, vomiting and insomnia, have been reported after abrupt discontinuation of high-dose antipsychotics. Cases of relapse of psychotic symptoms and involuntary movement disorders (such as akathisia, dystonia and dyskinesia) have been reported with amisulpride. Therefore, gradual discontinuation 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).
Benign pituitary tumour. Amisulpride may increase prolactin levels. Benign pituitary tumours such as prolactinoma have been reported with amisulpride treatment (see section 4.8). In the presence of very high prolactin levels or clinical signs of a pituitary tumour (such as visual field defects and headache), imaging studies should be performed to assess the pituitary gland. If a diagnosis of a pituitary tumour is confirmed, amisulpride treatment should be discontinued (see section 4.8).
Hepatotoxicity: Cases of severe hepatotoxicity have been reported with amisulpride. Patients should be advised to seek medical advice immediately if they develop any signs of liver damage, such as asthenia, anorexia, nausea, vomiting, abdominal pain or jaundice. Immediate medical evaluation, including clinical assessment and liver function tests, is required (see section 4.8).
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 investigation.
It is not recommended to use this medicine in combination with alcohol, dopaminergic antiparkinsonian drugs, antiparasitic drugs that can provoke torsades de pointes; with methadone, levodopa, other neuroleptics or drugs that can provoke torsades de pointes, sodium oxybutyrate and hydroxychloroquine (see section "Interaction with other medicinal products and other types of interactions").
Excipients: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
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 5.3). Amisulpride is not recommended during pregnancy unless the potential benefit justifies the potential risk.
Neonates whose mothers have been exposed to 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 following birth (see section 4.8). Adverse reactions such as agitation, hypertonia, hypotension, tremor, somnolence, respiratory distress syndrome or difficulty feeding have been reported. Therefore, close monitoring of the neonate is necessary.
Breastfeeding. Amisulpride is excreted in breast milk in a fairly large amount, which in some cases exceeds the accepted value of 10% of the mother's weight-adjusted dose. However, there are no data on the concentration of amisulpride in the blood of breast-fed infants. There is insufficient information on the effects of amisulpride on newborns/infants. It is necessary to weigh the benefit of breastfeeding for the infant and the benefit of amisulpride treatment for the mother and make a decision to discontinue breastfeeding or to discontinue amisulpride treatment.
Fertility: In animals, a decrease in fertility was observed, which is associated with the pharmacological effects of the drug (prolactin-mediated effect).
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 or blurred vision when taking this medicine (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 exceeding 400 mg per day should be divided into 2 doses.
Acute psychotic episodes. Treatment can be initiated with intramuscular administration of the drug in an appropriate dosage form for several days at a maximum dose of 400 mg/day, followed by oral administration. Doses of 400 mg/day to 800 mg/day are recommended to be administered orally. The maximum oral dose should in no case exceed 1200 mg/day. The safety of doses greater than 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 individualized at the lowest effective dose.
Predominantly negative episodes. Recommended doses range from 50 mg/day to 300 mg/day. Doses should be individualized. The optimal dose is approximately 100 mg/day.
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 (under 18 years of age) 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, as the safety of this medicinal product in this category of patients has not yet been established (see section "Contraindications").
Elderly patients. The safety of amisulpride in elderly patients has been evaluated in a limited number of patients. This drug should be used with caution in this subgroup of patients due to the risk of hypotension and sedative effects. A dose reduction may also be required in patients with renal insufficiency (see section 4.4).
Renal insufficiency. Since amisulpride is excreted by the kidneys, in renal insufficiency with creatinine clearance 30-60 ml/min the daily dose should be reduced by half, and in renal insufficiency with creatinine clearance 10-30 ml/min - by a third. Due to insufficient data in patients with severe renal insufficiency (CC < 10 ml/min), close monitoring of the condition of such patients is recommended (see section "Special instructions").
Hepatic impairment: Since the drug is poorly metabolized, dose reduction is not required.
Children. The efficacy and safety of amisulpride in children during puberty and 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. Therefore, the use of amisulpride in this category of patients 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
There is currently limited data on acute overdose with amisulpride. The signs and symptoms reported are mainly the result of increased pharmacological activity, clinically manifested by drowsiness, sedation, coma, hypotension and extrapyramidal symptoms. Fatalities have been reported, mainly 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 drug compound are limited.
Side effects
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 (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from the available data).
Nervous system disorders: Very common: extrapyramidal symptoms (tremor, hypertonia, increased salivation, akathisia, hypokinesia, dyskinesia). In most cases, they are mild at optimal doses and partially reversible without discontinuation of amisulpride when anticholinergic antiparkinsonian agents are prescribed.
The dose-dependent incidence of extrapyramidal symptoms is very low in patients receiving doses of 50–300 mg/day for predominantly negative symptoms.
Common: acute dystonia (spastic torticollis, oculogyric crisis, trismus), which 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.
Rare: neuroleptic malignant syndrome, which can be fatal (see section "Special warnings and precautions for use").
Frequency unknown: restless legs syndrome.
Psychiatric disorders: Common: insomnia, anxiety, agitation, frigidity. Uncommon: confusion.
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.
Rare: benign pituitary tumor such as prolactinoma (see sections "Contraindications" and "Special warnings and precautions for use").
Metabolism and nutrition disorders: Uncommon: hyperglycemia (see section "Special warnings and precautions for use"), hypertriglyceridemia and hypercholesterolemia.
Rare: hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SADH).
Cardiac disorders: Uncommon: bradycardia.
Rare: QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest, sudden death (see section "Special warnings and precautions for use").
Respiratory, thoracic and mediastinal disorders: Uncommon: nasal congestion, aspiration pneumonia (mainly in the case of concomitant use of other antipsychotics and CNS depressants).
Investigations: Common: weight gain. Uncommon: increased liver enzymes, mainly transaminases, have been reported. Frequency not known: increased blood creatine phosphokinase.
Immune system disorders: Uncommon: allergic reactions.
On the part of the organs of vision. Common: blurred vision (see section "Ability to influence the speed of reactions when driving vehicles or other mechanisms").
Hepatobiliary disorders: Uncommon: hepatocellular damage.
Skin and subcutaneous tissue disorders: Rare: angioedema, urticaria. Frequency unknown: photosensitivity reaction.
Musculoskeletal and general disorders: Uncommon: osteopenia, osteoporosis.
Frequency unknown: rhabdomyolysis.
Renal and urinary disorders: Uncommon: urinary retention.
Injury, poisoning and procedural complications: Frequency not known: falls due to adverse reactions leading to imbalance.
Blood and lymphatic system disorders: Uncommon: leukopenia, neutropenia (see section 4.4). Rare: agranulocytosis (see section 4.4).
Vascular disorders: Common: hypotension Uncommon: increased blood pressure Rare: cases of venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis have been reported with antipsychotics (see section 4.4).
Reporting of adverse reactions. Reporting of adverse reactions after registration of a medicinal product is important. This allows 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 cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua
Expiration date
3 years.
Storage conditions
Store in original packaging out of the reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Medochemie LTD (Central Factory).
Address
1-10 Constantinoupoleos Street, Limassol, 3011, Cyprus.
