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Active ingredients
Amisulpride
Release form
Pills
Composition
Amisulpride 200 mg; Auxiliary substances: sodium carboxymethylcellulose (sodium amylopectin glycolate) (type A) - 48 mg, lactose monohydrate - 139.2 mg, microcrystalline cellulose - 72 mg, hypromellose - 13.6 mg, magnesium stearate - 7.2 mg.
Pharmacological effect
Antipsychotic drug (neuroleptic) .; Amisulpride is an antipsychotic drug from the group of substituted benzamides. The pharmacodynamic profile of amisulpride is due to the selective and preferential affinity for the dopaminergic receptors of the limbic system of the D2 and D3 subtypes. Amisulpride does not have affinity for serotonin and other neuroreceptors, such as histamine, cholinergic and adrenergic receptors .; Animal studies have shown that when used in high doses, amisulpride more blocks the dopaminergic neurons of the mesolimbic system than similar neurons in the striatum system. This specific affinity apparently explains the predominance of the antipsychotic effects of amisulpride over its extrapyramidal effects .; When used in low doses, amisulpride predominantly blocks presynaptic D2 and D3 dopaminergic receptors, which may explain its positive effect on negative symptoms.
Pharmacokinetics
Absorption; After taking the drug inside, there are two peaks of absorption of amisulpride: one is reached after 1 hour, and the second between 3 and 4 hours after ingestion. After taking the drug in a dose of 50 mg Cmax of amisulpride in plasma, corresponding to these peaks are 39 ± 3 ng / ml and 54 ± 4 ng / ml. Absolute bioavailability of 48% .; Food rich in carbohydrates reliably reduces AUC, Tmax and Cmax of amisulpride, while fat-rich food does not cause any changes in the above pharmacokinetic parameters. However, the significance of these observations in everyday clinical practice is unknown .; Distribution; Vd is equal to 5.8 l / kg. Due to the low degree of binding to plasma proteins (16%), no interaction of amisulpride with other drugs is expected at the level of protein binding. In the course application, cumulation of amisulpride does not occur, and its pharmacokinetics do not change .; Metabolism and excretion; Amisulpride is slightly metabolized in the liver (about 4%). Two inactive metabolites have been identified. When ingested T1 / 2 amisulprid is approximately 12 hours. Excreted in the urine unchanged.Renal clearance is approximately 330 ml / min; Pharmacokinetics in special clinical situations; T1 / 2 in patients with renal insufficiency does not change, but systemic clearance decreases with a factor of 2.5 to 3. AUC of amisulpride in mild renal insufficiency is doubled, and in moderate renal insufficiency it is almost tenfold. Experience with the use of the drug in renal failure is limited, there are no data on the use of amisulpride in a dose exceeding 50 mg. Amisulpride is practically not excreted by hemodialysis .; Due to the fact that amisulpride is slightly metabolized in the liver, there is no accumulation of the drug in case of liver failure, therefore, a dose reduction is not required .; When comparing the pharmacokinetic parameters of patients over 65 years of age with those of younger patients, it was found that after a single dose of amisulpride orally at a dose of 50 mg, the Cmax, T1 / 2 and AUC values are 10-30% higher. Data on pharmacokinetics in elderly patients with course administration of amisulpride are not available.
Indications
- acute and chronic schizophrenia, accompanied by productive (including delusions, hallucinations, mental disorders) and / or negative symptoms (including affective flattening, loss of emotional and social ties), including in patients with a predominance of negative symptoms.
Contraindications
- concomitant prolactin-dependent tumors (including pituitary prolactinoma, breast cancer); - pheochromocytoma; - severe renal failure with CC <10 ml / min (no clinical experience); - combined use with dopamine receptor agonists (including cabergoline, quinagolide), with the exception of patients with Parkinson's disease; - combined use with levodopa, amantadine, apomorphine, bromocriptine, entacapone, lizuridom, pergolid, piribedilom, pramipexol, ropinerol, selegilinom; - combined use with drugs that can prolong the QT interval and cause the development of rhythm disturbances, including potentially life-threatening polymorphic ventricular tachycardia of the “pirouette” type, such as antiarrhythmic drugs of class IA (quinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide,ibutilil), other drugs (bepridil, cisapride, methadone, sultoprid, thioridazine, diphemanyl methyl sulfate, erythromycin for iv administration, spiramycin for iv injection, mizolastine, vincamine for iv injection, halofantrin, lumefantrin, sparfarfarfarfarf, infarf, sparfarf, sypharfarf, infarman, vincamine for iv administration pentamidine); - children's age up to 18 years; - lactation period (breastfeeding); - congenital galactosemia, glucose or galactose malabsorption syndrome, lactase deficiency; - hypersensitivity to amisulpride and other components of the drug .; The drug should be used with caution in patients: - with predisposing factors for the development of severe ventricular arrhythmias, including the potentially life-threatening pancreatitis on the pancreatitis (torsade des pointes) (amisulpride is capable of prolonging the QT interval and increasing the risk of developing severe ventricular arrhythmias including ventricular, including ventricular, including ventricular). like "pirouette" (torsade des pointes); - with a congenital prolonged QT interval; - with acquired prolongation of the QT interval (when combined with drugs that increase the duration QTc interval, with the exception of those indicated in the section "Contraindications"; - with bradycardia less than 55 bpm; - with electrolyte disorders, including hypokalemia; - receiving concomitant therapy with drugs capable of causing hypokalemia, expressed bradycardia less than 55 b / min, slow down intracardiac conduction; - with renal insufficiency, because there is a risk of drug accumulation, and experience with its use in renal insufficiency is limited; - in elderly patients, because there is an increased predisposition to lower blood pressure and the development of excessive sedation; - in elderly patients with dementia; - with risk factors for stroke; - with epilepsy, because amisulpride can reduce the threshold of convulsive readiness; - with risk factors for thromboembolism; - with Parkinson's disease, because Amisulpride, like other anti-dopaminergic drugs, may increase the symptoms of Parkinson's disease; - with diabetes mellitus and patients with risk factors for the development of diabetes mellitus (because some atypical antipsychotics, including amisulpride, may cause an increase in blood glucose concentration).
Use during pregnancy and lactation
The safety of using amisulpride during pregnancy has not been established. Consequently, the use of the drug during pregnancy is not recommended, except in cases where the intended benefit to the mother justifies the potential risk to the fetus .; In newborns who have been exposed to intrauterine antipsychotic drugs, including Solian; during the third trimester of pregnancy, there is a risk of adverse reactions after birth, including extrapyramidal symptoms or withdrawal syndrome, which can vary in severity and duration. It has been reported about the development of arousal, muscular hypertonia, muscular hypotonia, tremor, drowsiness, respiratory disorders or difficulties during breastfeeding. Therefore, these newborns must be under constant medical supervision .; It is not known whether amisulpride is excreted in breast milk, so the use of the drug during lactation is contraindicated.
Dosage and administration
Usually, if the daily dose does not exceed 400 mg, the drug can be taken 1 time / day, if the daily dose exceeds 400 mg, then it should be divided into 2 doses .; With the prevalence of negative symptoms, the recommended daily dose varies from 50 to 300 mg (on average, 100 mg / day). Selection of doses should be carried out individually. If the dose is less than 200 mg, pills should be taken Solian; 100 mg or 200 mg. In mixed episodes with negative and productive symptoms, the doses should be selected so as to ensure optimal control over productive symptoms: on average, from 400 mg to 800 mg / day. Maintenance treatment should be set individually at the level of the minimum effective dose (depending on the response of the patient) .; In acute psychotic episodes at the beginning of treatment, the recommended dose is 400 to 800 mg / day. The maximum daily dose should not exceed 1200 mg. For maintenance therapy, the selected dose is maintained or adjusted depending on the response of the patient. In all cases, maintenance doses should be set individually at the level of the minimum effective dose .; In case of renal insufficiency, the dose for patients with QC from 30 to 60 ml / min should be reduced by half, with QC from 10 to 30 ml / min - three times.Due to the lack of data on the use of the drug in patients with QA <10 ml / min, the use of amisulpride is contraindicated in this group of patients .; Due to the fact that the drug is poorly metabolized in the liver, reducing its dose in liver failure is not required .; Elderly Patients Solian; should be prescribed with extreme caution .; The efficacy and safety of the use of amisulpride in children and adolescents under the age of 15 years have not been established. There are limited data on the use of amisulpride in adolescents with schizophrenia, so the use of the drug in patients aged 15 to 18 years is not recommended, the use of the drug in children and adolescents under the age of 15 years is contraindicated.
Side effects
Side effects are presented in accordance with the following gradation of the frequency of their occurrence: very often (≥10%), often (≥1%, <10%), infrequently (≥0.1%, <1%), rarely (≥0.01%, <0.1 %), very rarely, including individual messages (<0.01%), unknown frequency (it is not possible to determine the frequency from the available data) .; Below are the side effects observed in controlled clinical trials and post-marketing use of the drug. It should be noted that in some cases it is very difficult to differentiate the side effects from the symptoms of the underlying disease .; On the part of the nervous system; Very often - extrapyramidal symptoms (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia), which are usually moderately pronounced when used in optimal doses and partially reversible with the addition of anticholinergic anti-parkinsonian drugs without discontinuing treatment with amisulfride. The frequency of extrapyramidal symptoms depends on the dose. Therefore, in patients with predominantly negative symptoms, taking amisulpride at a dose of 50-300 mg, the frequency of extrapyramidal disorders is very low .; Often - insomnia, anxiety, agitation, impaired orgasm, daytime sleepiness; acute dystonias (spastic torticollis, oculariologic crises, trismism), reversible with the addition of anticholinergic anti-parkinsonian drugs without discontinuing treatment with amisulfride .; Infrequently - attacks of spasms; late dyskinesias characterized by rhythmic, involuntary movements of the tongue and / or facial muscles, usually occurring after prolonged use of the drug.Anticholinergic anti-parkinsonian drugs in these cases are ineffective or may increase symptoms .; Unknown frequency - neuroleptic malignant syndrome .; On the part of the digestive system: often - constipation, nausea, vomiting, dry mouth; infrequently - an increase in the activity of liver enzymes, mainly transaminases .; On the part of the endocrine system: often - an increase in the concentration of prolactin in the blood plasma (reversible after discontinuation of the drug), which can cause galactorrhea, amenorrhea, gynecomastia, breast pain, erectile dysfunction; weight gain; infrequently - hyperglycemia .; Since the cardiovascular system: often - a decrease in blood pressure; infrequently - bradycardia; unknown frequency - prolongation of the QT interval, ventricular arrhythmias such as polymorphic ventricular tachycardia of the "pirouette" type, which can turn into ventricular fibrillation and lead to cardiac arrest and sudden death, venous thromboembolic complications, including pulmonary embolism, sometimes fatal, and thrombosis deep veins .; On the part of the immune system: rarely - allergic reactions; unknown frequency - angioedema, urticaria .; From the side of the hemopoietic system: unknown frequency - leukopenia, neutropenia, agranulocytosis.
Overdose
Symptoms: increased known pharmacological effects of the drug (including drowsiness, sedation, hypotension, extrapyramidal symptoms, coma). There have been reports of deaths in overdose, mainly when combined with other psychotropic drugs. It should be borne in mind that the phenomenon of overdose can occur in cases of erroneous use of additional doses of the drug or the simultaneous use of other drugs .; Treatment: the main vital functions of the body should be monitored and maintained up to the patient’s complete exit from the state of overdose. It is obligatory to conduct ECG monitoring, since there is a risk of lengthening the QT interval and the development of life-threatening rhythm disorders. If serious extrapyramidal symptoms occur, m-anticholinergic blockers should be used. Sinceremoval of amisulpride using hemodialysis is insignificant, then for its removal in overdose the use of hemodialysis is impractical. There is no specific antidote for amisulpride.
Interaction with other drugs
Contraindicated combinations; Simultaneous use with drugs capable of lengthening the QT interval and causing paroxysmal tachycardias, including potentially lethal polymorphic ventricular pirouette tachycardia: - Class IA antiarrhythmic drugs (quinidine, disopyramide) and class III (amiodarone, sotalol, in the form of class III (quinidine, disopyramide) and class III (amiodarone, sotalol, in the form of class III (quinidine, disopyramide) and class III (amiodarone, sotalol, in the form of IA class (quinidine, disopyramide)) and class III (amiodarone, sotalol, eye strain of the I class of quinidine, disopyramide) and class III (amiodarone, sotalol, class I, 3) (i.e. ; - bepridil, cisapride, methadone, sultoprid, thioridazine, diphemethyl methyl sulfate, erythromycin (w / w), spiramycin (w / w), mizolastin, vincamine (w / w), halofantrin, lumefantrin, sparfloxacin, hatifloxcin, and halofantrin, lumefantrine, sparfloxacin, hatifloxcin, and halofantrin, lumefantrine, sparfloxacin, hatifloxcin, and halofantrin; The risk of paroxysmal tachycardia, including potentially lethal polymorphic ventricular tachycardia of the “pirouette” type, is simultaneously increased with simultaneous use: - with dopamine receptor agonists (cabergoline, quinagolide) when they are not used to treat Parkinson's disease (cross-antagonism of the effects of the dopamine receptors on the body patterns and body patterns), in addition to the effects of gidrosamine receptors on hysteric tachycardia (papamine, quinagolide); may cause or exacerbate psychotic symptoms, amisulpride may exacerbate the symptoms of Parkinson's disease); - with levodopa (reciprocal antagonism of the effects of levodopa and neuroleptics) .; Not recommended combinations; Not recommended simultaneous application with the drugs that increase the risk of a potentially fatal polymorphic ventricular tachycardia type "pirouette" - drugs that cause bradycardia (beta-blockers, verapamil, diltiazem, clonidine, guanfacine, digitalis drugs, donepezil, rivastigmine, tacrine, ambenonium chloride, galantamine, pyridostigmine bromide, neostigmine bromide); - drugs that cause hypokalemia (diuretics that cause hypokalemia, simulating intestinal motility, laxatives, amphotericin B for intravenous administration, GCS, tetracosactids) - it is necessary to restore potassium losses and maintain a normal level of potassium in the blood; - some neuroleptics (haloperidol, pimozide, pipotiazin, sertindol, chlorpromazine, levomepromazine, cyamemazine, sultopride, sulpiride, Tiapride, veralipride, droperidol), imipramine antidepressants, preparations of lithium, anti-fungal drugs Not recommended simultaneous use with ethanol, becauseamisulpride enhances the central effects of ethanol, and ethanol enhances the sedative effects of neuroleptics .; With simultaneous use with dopamine receptor agonists (amantadine, apomorphine, bromocriptine, entacapone, lizurid, pergolid, piribedil, pramipexol, ropinirole, selegilin), psychotic symptoms may develop or strengthen as a result of mutual antagonism. Amisulpride may increase the symptoms of Parkinson's disease; With simultaneous use with CNS depressant drugs (morphine derivatives (analgesics, antitussive drugs), barbiturates, benzodiazepines, non-benzodiazepine anxiolytics, sleeping pills, antidepressants with sedative effects (amitriptyline, docsepine, in a medication, anesthesia, anesthesia, anesthesia, anesthesia, anesthesia, anesthesia, anesthesia, a sedative effect) (an amitriptyline, a dexepin, an exercise therapy, an anti-depressant, anesthetics, a sedative effect) ), H1-histamine receptor blockers with a sedative effect, antihypertensive drugs of central action (clonidine), antipsychotics, baclofen, thalidomide, pizothiphene) is noted in expressions increased inhibitory action on the central nervous system, an additional reduction in the concentration of attention, which creates a great danger to motorists and persons working with machinery .; With simultaneous use with antihypertensive drugs, including beta-blockers (bisoprolol, carvedilol, metoprolol) increases the risk of arterial hypotension, in particular orthostatic hypotension (additive effect).
special instructions
According to a controlled double-blind study comparing amisulpride and haloperidol in patients with acute schizophrenia (191 patients), a significantly greater reduction in secondary negative symptoms was observed with the use of amisulpride. According to clinical studies with the use of amisulpride, a significantly lower frequency of extrapyramidal symptoms was observed than with the use of haloperidol. As with the use of other neuroleptics, with the use of amisulpride (especially in high doses), a neuroleptic malignant syndrome can develop, a potentially fatal complication characterized by hyperthermia, muscle rigidity, autonomic disorders, increased concentration of CPK.With the development of hyperthermia, especially against the background of the use of antipsychotics in high doses, all antipsychotic drugs, including amisulprid, should be canceled .; Care must be taken when prescribing anti-dopaminergic agents and, in particular, amisulpride in Parkinson's disease, since with his appointment may worsen the course of this disease. In patients with Parkinson’s disease, amisulpride should be used only if it cannot be avoided. If a patient with Parkinson's disease receiving dopamine receptor agonists needs treatment with amisulpride, then dopamine receptor agonists should be discontinued gradually (by gradually reducing the dose until they are completely eliminated), because abrupt cancellation can lead to the development of neuroleptic malignant syndrome .; For correction of extrapyramidal symptoms that arose during treatment with amisulpride, central m-anticholinergic blockers should be used (and not dopamine receptor agonists) .; Due to the fact that amisulpride causes a dose-dependent increase in the duration of the QT interval, its use increases the risk of paroxysmal tachycardias, including the potentially life-threatening polymorphic ventricular pirouette tachycardia. Therefore, if the patient's condition allows, it is recommended to conduct an ECG and examine the electrolyte composition of blood before identifying and, if possible, correct factors that may contribute to such dangerous disturbances, rhythm (bradycardia <55 beats / min, hypokalemia, hypomagnesia, congenital or acquired prolonged QT interval, simultaneous administration of drugs capable of causing marked bradycardia (<55 beats / min), hypokalemia, slowing of intracardiac conduction, increase pro olzhitelnost QT interval) .; During treatment with amisulpride, alcohol and preparations containing ethanol should not be taken .; Due to the ability of the drug to lower the threshold of convulsive readiness, when using amisulpride, patients with epilepsy should be carefully clinically and, if possible, electroencephalographically observed .; Some atypical antipsychotics, including amisulpride, can cause an increase in blood glucose concentration.In patients with diabetes mellitus and patients with risk factors for the development of diabetes mellitus, the use of amisulpride should regularly monitor blood glucose concentrations .; In elderly patients, amisulpride, like other antipsychotics, should be used with extreme caution because of the possible risk of hypotension or excessive sedation .; In randomized clinical trials compared with placebo in a group of elderly patients with dementia who received treatment with some atypical antipsychotics, there was a threefold increase in the risk of developing cerebrovascular events (acute disorders of cerebral circulation). The mechanism for this increase in risk is not known. An increase in such a risk with the use of other antipsychotic drugs or in other groups of patients cannot be ruled out .; Amisulpride should be used with caution in patients with stroke risk factors .; In older patients with dementia-related psychosis, treatment with antipsychotic drugs was associated with an increased risk of death. An analysis of 17 placebo-controlled studies (with an average duration of more than 10 weeks) showed that the majority of patients taking atypical antipsychotic drugs had a 1.6–1.7 times greater risk of death than patients taking placebo. Although the causes of death in clinical trials with atypical antipsychotic drugs varied, most causes of death were either cardiovascular (for example, heart failure, sudden death), or infectious (for example, pneumonia) by nature. Observational studies have confirmed that, like treatment with atypical antipsychotics, treatment with conventional antipsychotics can also increase mortality. The extent to which the increase in mortality may be due to antipsychotic drugs, and not some of the characteristics of patients, is not clear .; With a sharp cessation of the administration of neuroleptics in high therapeutic doses, cases of the development of the syndrome have been described; When using amisulpride, the occurrence of involuntary movement disorders such as akathisia, muscle tone disorder and dyskinesia have been reported. Therefore, a gradual reduction of the dose is recommended with the abolition of amisulprid .; When using antipsychotic drugs, cases of venous thromboembolic complications, sometimes fatal, were observed.Therefore, amisulpride should be used with caution in patients with risk factors for venous thromboembolic complications .; The removal of amisulpride is carried out by the kidneys. In case of impaired renal function, the dose should be reduced .; When using antipsychotic drugs, including Solian ;, leukopenia, neutropenia and agranulocytosis were observed. Unexplained infections or fever may be a manifestation of blood disorders and require immediate examination .; Impact on the ability to drive vehicles and control mechanisms; Patients, especially those who are drivers of vehicles or engaged in other potentially dangerous activities, should be informed about the possibility of drowsiness and reduced psychomotor reactions during the use of amisulpride, t. to. this can be dangerous when driving and working with machinery.