Expiration date: 03/2025
Composition
1 ml of oral solution contains:
Active substance
Amisulpride - 100 mg.
Excipients
Gesvit - 4 g (containing sodium saccharin (75-85%), glyukurolakton (15-20%), sodium gluconate (<March 5 = "" - = "" ph = "" 4 = "" = 5.6 " "5 =" "8 =" "= 100" "= 50" "200 =" "1 =" "p =" ">,
60 ml vial oral solution. The package 1 vial.
Indications
Schizophrenia:
Acute or chronic schizophrenic disorders with positive symptoms (delusions, hallucinations, thought disorders) and / or negative symptoms (flattening of affect, loss of emotional and social ties), including patients with predominantly negative symptoms.
Pharmacokinetics
Absorption and distribution
Amisulpride have observed two absorption peaks: one is reached rapidly, within an hour, and the second - between 3 and 4 hour after ingestion. Suitable concentrations in plasma after ingestion of 50 mg is 39 ± 3 ng / ml and 54 ± 4 ng / ml, respectively.
The volume of distribution of 5.8 l / kg. Due to the low bond to plasma proteins (16%), are not expected to interact with other medications amisulpride level communication with the protein. The absolute bioavailability is 48%.
Metabolism and excretion
Amisulpride significantly metabolized in the liver (approximately 4%), identified two inactive metabolite. In exchange taking amisulpride accumulation does not occur, and the pharmacokinetics does not change. If ingestion T 1/2 amisulpride is approximately 12 hours. Amisulpride is excreted in the urine in unchanged form. Renal clearance is approximately 330 ml / min.
Pharmacokinetics in special clinical situations
Carbohydrate-rich diet significantly reduced AUC, time to maximum concentration (T max) in the blood plasma itself amisulpride maximum concentration in plasma (C max), while food rich in fats aforementioned pharmacokinetic parameters change causes. However, the significance of these observations in everyday clinical practice is unknown.
kidney failure
The half-life in renal failure patients does not change, but the systemic clearance is reduced by 2.5-3 times. AUC amisulpride with mild renal insufficiency doubled, and in renal failure of moderate severity - almost tenfold. Experience with the drug in renal failure is limited, and there is no data in the reception amisulpride dose greater than 50 mg. Amisulpride virtually displayed by hemodialysis.
Hepatic nedostatochnost
Due to the fact that amisulpride significantly metabolized in the liver, the drug is not expected to accumulate in hepatic failure and reduce its dose is not required.
Elderly patients
When comparing the pharmacokinetic parameters of patients over 65 years with those of younger patients found that they have after a single oral administration of amisulpride 50 mg values ??of C max, T 1/2 and AUC higher by 10-30%. Data on the pharmacokinetic parameters in the elderly amisulpride at course intake no.
Clinical pharmacology
Amisulpride is an antipsychotic drug from the group of substituted benzamides. Amisulpride pharmacodynamic profile caused by selective and preferential affinity for subtypes of D2 and D3-dopamine receptor limbic system. Amisulpride has no affinity for serotonin and other neuroreceptors such as histamine, cholinergic and adrenergic receptors.
In animal studies, it was shown that when taken in high doses, amisulpride more blocks dopaminergic neurons of the mesolimbic system than a similar system neurons in striatum. This is explained by the specific affinity, presumably, antipsychotic effects amisulpride predominance over its extrapyramidal effects.
When used in low doses amisulpride predominantly blocks presynaptic D2 and D3-dopamine receptors, than can be explained by its positive influence on the negative symptoms.
According to the controlled double-blind study compared amisulpride and haloperidol in acute schizophrenia patients (191 patients) was observed in the application of amisulpride significantly greater decrease in secondary negative symptoms. According to clinical studies with the use of amisulpride observed a significantly lower incidence of extrapyramidal symptoms than with haloperidol.
Pregnancy and breast-feeding
Pregnancy
Safety has not been established receiving amisulpride during pregnancy. Therefore, the use of the drug during pregnancy is not recommended unless the expected benefit to the mother justifies the potential risk to the fetus. Newborns exposed during the third trimester in utero effects of neuroleptics, including Solian, are at risk of adverse reactions including extrapyramidal syndrome or syndrome of "cancellation", which can vary in severity and duration following delivery. It reported the development of excitation, muscular hypertonicity, tremors, drowsiness, respiratory disorders or disorders in infants. Therefore, these babies need careful monitoring of their condition.
Lactation
It is not known whether amisulpride is able to penetrate into the breast milk, so breast-feeding at the time of his admission is contraindicated.
Contraindications
Hypersensitivity to amisulpride or to other components of the preparation.
Related prolaktinzavisimye tumors, eg pituitary gland prolactinoma and breast cancer.
Confirmed pheochromocytoma, suspected pheochromocytoma.
Children and teens under 18 years of age (no experience clinical application).
The period of lactation.
Severe renal insufficiency with creatinine clearance less than 10 ml / min (no clinical experience).
Concomitant treatment with cabergoline, quinagolide.
Concomitant levodopa therapy.
Concomitant medication therapy, able to lengthen the QT interval and cause the development of arrhythmias, including potentially life-threatening ventricular tachycardia type "pirouette» (torsade des pointes): antiarrhythmics IA class drugs (quinidine, disopyramide) and class III (amiodarone, sotalol, dofetilide, Ibutilide).
Other medications (bepridil, cisapride, methadone, sultopride, thioridazine, difemanila methyl sulfate, injectable erythromycin, spiramycin injectable, mizolastine, vincamine given intravenously, halofantrine, Lumefantrine, sparfloxacin, moxifloxacin, pentamidine, etc.).
Carefully:
In patients with predisposing factors for severe ventricular arrhythmias, including potentially life-threatening ventricular tachycardia type "pirouette" (torsade des pointes) (amisulpride is able to dose-dependently prolong the QT interval and increase the risk of serious ventricular arrhythmias, including ventricular tachycardia type "pirouette" (torsade des pointes).
In patients with congenital long QT interval.
Combination with drugs that increase the duration of the QT interval, except for those specified in section.
Patients with Bradycardia less than 55 beats per minute.
Patients with electrolyte disturbances, including hypokalaemia.
In patients receiving concomitant therapy with drugs capable of causing hypokalemia, bradycardia less than 55 beats per minute, to slow intracardiac conduction.
In patients with renal impairment, as there is a risk of cumulation of the drug, and the experience of its use in patients with renal insufficiency is limited.
Elderly patients, as they have an increased predisposition to lower blood pressure and the development of excessive sedation.
Elderly patients with dementia.
Patients with risk factors for stroke.
In patients with epilepsy, as amisulpride may lower the seizure threshold.
Patients with risk factors for thromboembolism.
Patients with Parkinson's disease, as amisulpride antidofaminergicheskie as other drugs may enhance the manifestations of Parkinson's disease.
In patients with diabetes and patients with risk factors for diabetes (as some atypical antipsychotics, including amisulpride, may cause an increase in blood sugar levels).
Side effect
Side effects reported in accordance with the following gradations their frequency of occurrence:
Very frequent (?10%).
Common (?1%, <, 10 li = "">,
Infrequent (?0,1%, <, 1 li = "">,
Rare (?0,01%, <, 0,1 li = "">,
Very rare, including isolated reports (<, 0,01 li = "">,
Unknown frequency (according to available data to determine the frequency of occurrence of adverse effects is not possible).
The following are the side effects observed in controlled clinical trials and post-marketing use of the drug. It should be noted that in some cases very difficult to differentiate the side effects on the symptoms of the main disease.
Disorders of the central nervous system
Very frequent - extrapyramidal syndromes (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia). These symptoms are usually moderate in intensity when taken in optimal doses and partially reversible with the addition of anticholinergic antiparkinsonian drugs amisulpride without discontinuation of treatment. The incidence of extrapyramidal symptoms depends on the dose. Therefore, in patients with predominantly negative symptoms, amisulpride receiving a dose of 50-300 mg, the incidence of extrapyramidal disorders is very low. According to clinical studies with the use of amisulpride observed a significantly lower incidence of extrapyramidal symptoms than with haloperidol.
Frequent - Acute dystonia (spasmodic torticollis, oculogyric crises, lockjaw), reversible with the addition of anticholinergic antiparkinsonian drugs amisulpride without discontinuation of treatment. Daytime sleepiness.
Infrequent - late dyskinesia characterized by rhythmical, involuntary movements mainly language and / or facial muscles, usually occurring after long-term administration of the drug. Anticholinergic antiparkinsonian drugs in these cases not be effective or may exacerbate symptoms. Seizures and convulsions.
Unknown frequency - neuroleptic malignant syndrome, a potentially fatal complication.
Violations of the psyche
Frequent - Insomnia anxiety, agitation, orgasmic disorders.
Violations of the digestive tract
Frequent - constipation, nausea, vomiting, and dry mouth.
Disorders of the endocrine system
Frequent - amisulpride causes an increase in plasma concentrations of prolactin, reversible after discontinuation of the drug. This can lead to galactorrhea, amenorrhea, gynecomastia, breast pain, and erectile dysfunction.
Metabolic disorders
Frequent - weight gain.
Infrequent - hyperglycemia.
Violations of the cardiovascular system
Frequent - lowering blood pressure.
Infrequent - bradycardia.
Unknown frequency - lengthening the interval QT, ventricular arrhythmias such as polymorphic ventricular tachycardia type "pirouette" (torsade des pointes), which can go into ventricular fibrillation and lead to cardiac arrest and sudden death. Thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis.
Violations by the laboratory parameters
Infrequent - increased activity of "liver" enzymes, mainly transaminases in the blood.
Violations by the immune system
Infrequent - allergic reactions.
Unknown frequency - angioedema and urticaria.
Violations of the blood and lymphatic system
Unknown frequency - leukopenia, agranulocytosis and neytropeiiya.
Pregnancy, postnatal and perinatal conditions
Unknown frequency - a syndrome of "cancellation" in neonates.
Interaction
contraindicated combinations
With drugs, able to lengthen the QT interval and cause paroxysmal tachycardia, including potentially lethal polymorphic ventricular tachycardia type "pirouette" (torsade des pointes):
With Class 1A antiarrhythmics (quinidine, disopyramide), and Class III (amiodarone, sotalol, dofetilide, Ibutilide).
With bepridilom, cisapride, methadone, sultopride, thioridazine, difemanila methyl sulfate, erythromycin (iv), spiramycin (intravenously), mizolastine, vincamine (intravenously), halofantrine, Lumefantrine, sparfloxacin, gatifloxacin, moxifloxacin, pentamidine, etc. It increases the risk of paroxysmal tachycardia, including potentially lethal ventricular tachycardia type "pirouette" (torsade des pointes).
Since dopamine receptor agonist (cabergoline, quinagolide).
Mutual antagonism of the effects of dopamine receptor agonists and neuroleptics. Dopamine receptor agonists may cause or exacerbate psychotic symptoms.
Since levodopa.
Reciprocal antagonism of the effects of levodopa and neuroleptics.
Not recommended combinations
With drugs that increase the risk of potentially lethal ventricular tachycardia type "pirouette" (torsade des pointes):
With drugs that cause bradycardia (beta-blockers, verapamil, diltiazem, klopidin, Mr. uanfatsin, digitalis drugs, donepezil, rivastigmine, tacrine, ambenonium chloride, galantamine, pyridostigmine, neostigmine bromide).
With drugs that cause hypokalemia (to cause hypokalemia diuretics, feigning intestinal peristalsis laxatives, intravenous amphotericin B, corticosteroids, tetrakozaktid) - when used, be sure to restore the loss of potassium and maintain a normal level of potassium in the blood, some antipsychotics (haloperidol, pimozide, pipotiazine, sertindole, chlorpromazine, levomepromazina, tsiamemazinom, sultopride, sulpiride, tiaprid, veralipridom, droperidol), imipraminovymi antidepressants, lithium, drugs, azole antifungals.
The risk of ventricular arrhythmias, especially ventricular tachycardia of "feasting" ( «torsade des pointes»).
With alcohol.
Amisulpride increases the central effects of alcohol. Alcohol increases the sedative effect of neuroleptics.
Since dopamine receptor agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline).
Mutual antagonism of the effects of dopamine receptor agonists and neuroleptics
Dopamine receptor agonists may cause or exacerbate psychotic symptoms. Amisulpride may exacerbate the symptoms of Parkinson's disease.
Combinations to be taken into account
With drugs depressing the central nervous system: derivatives of morphine (analgesics, anti-inflammatory drugs), barbiturates, benzodiazepines, no benzodiazepine anxiolytics, sleeping pills, antidepressants with sedative effect (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), H1-histamine blockers with sedation, hypotensive Centrally acting drugs (clonidine), antipsychotics, baclofen, thalidomide, pizotifenom.
Marked increased inhibitory action on CNS. An additional reduction in the concentration of attention, which creates a great danger to motorists and persons working with machinery.
With the antihypertensive drugs, including beta-blockers (bisoprolol, carvedilol, metoprolol).
The risk of hypotension, in particular postural hypotension (additive effect). With regard to beta-blockers further.
Overdose
Symptoms: The experience with overdose of amisulpride, is very limited. It reported a significant increase in the known pharmacological effects of the drug, namely the development of drowsiness, sedation, blood pressure lowering, extrapyramidal syndrome and coma. There were reports of fatal overdose, mainly in combination with other psychotropic drugs. It should be understood that an overdose phenomena can occur in cases of erroneous reception of additional doses or simultaneous administration of other drugs.
Treatment: the specific antidote to amisulpride not. In case of overdose should be monitored and to maintain basic vital functions of the body until the full release of the patient from a state of overdose. In case of overdose provedenieEKG -monitorirovaniya is a must, as there is a risk of QT prolongation and development of life-threatening rhythm disorders symptoms, should be used m-holinoblokatory central action, such as trihexyphenidyl.
Since excretion amisulpride by hemodialysis is negligible, then its elimination in overdose use of hemodialysis is impractical.
Dosing and Administration
The drug is intended for oral administration.
To open the bottle with the unit "protection of children" need to put pressure on the vial cap and turn it. Assigned dose is dialed with a syringe (1 ml contains 100 mg amisulpride).
Usually, if the daily dosage does not exceed 400 mg, it can be taken once a day, and if the daily dose of more than 400 mg, it must be divided into two steps.
With the predominance of negative symptoms
For patients with predominantly negative symptoms amisulpride designation recommended dose of 50 to 300 mg per day (on average 100 mg per day). dose selection should be carried out individually.
When mixed with episodes of productive and negative symptoms
For patients with mixed (productive and negative) symptoms dose should be selected so as to provide optimal control of productive symptoms, they comprise on average from 400 mg to 800 mg. Supportive care must be installed individually on the level of the minimum effective dose (depending on patient response).
Acute psychotic episodes
Starting treatment
Perhaps begin treatment by intramuscular injection for several days to a maximum dose of 400 mg / day with subsequent transfer to the ingestion of the drug.
For oral administration applied dose of 400 to 800 mg. The maximum dose should never exceed 1200 mg per day.
maintenance therapy
Subsequently, the selected dose is maintained or adjusted depending on the patient response. In all cases, the maintenance dose must be set individually at the level of the minimum effective dose.
In patients with renal insufficiency
Clinical experience with the drug in patients with impaired renal function is limited. Withdrawal amisulpride carried out through the kidneys. In renal insufficiency, the dose for patients with a creatinine clearance 30 - 60 ml / min should be reduced by half, and for patients with a creatinine clearance of 10 to 30 ml / minute - three times.
In the absence of data on the use of the drug in patients with creatinine clearance less than 10 ml / min, the use of amisulpride is contraindicated in this group of patients.
Patients with hepatic insufficiency
Due to the fact that the drug is poorly metabolized in the liver, the dose reduction in hepatic failure is not required.
children
Efficacy and safety of amisulpride in children and adolescents under 18 years of age have not been established. There are limited data on the use of amisulpride in adolescents in schizophrenia. In children and adolescents up to 18 years of use of amisulpride is contraindicated.
Elderly patients
Use of the drug with caution in elderly patients, since they have an increased susceptibility to blood pressure reduction and the development of excessive sedation.
Precautionary measures
As with other antipsychotics, amisulpride in the application (especially high doses) may develop neuroleptic malignant syndrome, a potentially lethal complication, characterized by hyperthermia, muscle rigidity, autonomic disorders, the high concentration of creatine kinase in the blood. With the development of hyperthermia, especially during treatment with high doses of neuroleptics, all antipsychotic drugs including amisulpride should be repealed.
Caution must be exercised in the appointment of blockers of dopamine receptors and in particular amisulpride in Parkinson's disease, since his appointment possible worsening of the disease. Patients with Parkinson's disease amisulpride should be used only if it is impossible to avoid their use. If a patient with Parkinson's disease receiving dopamine receptor agonists, amisulpride treatment is necessary, the dopamine receptor agonists should be withdrawn gradually (by gradually reducing the dose to complete their withdrawal), as abrupt withdrawal can lead to the development of neuroleptic malignant syndrome.
For correction of extrapyramidal syndromes occurred during treatment with amisulpride should be used anticholinergic antiparkinsonian drugs (not dopamine receptor agonists).
Due to the fact that amisulpride is a dose-dependent prolongation of the interval QT, the risk of increases in its admission of paroxysmal tachycardia, including potentially life-threatening ventricular tachycardia type "pirouette" (torsade des pointes). Therefore, if the conditions allow the patient before prescribing amisulpride is advisable to remove the ECG and explore the electrolyte composition of the blood, to identify and possibly correct the factors that may contribute to such dangerous arrhythmias (such as bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia, congenital or acquired QT prolongation of the interval, concomitant use of drugs that can cause severe bradycardia (less than 55 u. / min), hypokalaemia, slowing of intracardiac conduction, prolong the QT interval).
During treatment with amisulpride should not take alcohol and alcohol-containing medications.
Due to the drug's ability to lower the seizure threshold, while taking amisulpride patients with epilepsy after them should be careful clinical and, whenever possible, electroencephalographic monitoring.
Some atypical antipsychotics including amisulpride may cause a rise in blood sugar. In patients with diabetes and patients with risk factors for diabetes in the appointment of amisulpride should regularly monitor the blood sugar levels.
In elderly patients, amisulpride, like other neuroleptics, should be used with extreme caution because of the possible risk of reduction in blood pressure or development of excessive sedation.
In randomized clinical trials conducted in a group of elderly patients with dementia treated with some atypical antipsychotics, there was a threefold increase in the risk of cerebrovascular events compared with placebo. The mechanism for this increased risk is not known. We can not exclude an increase in this risk when using other antipsychotics or other groups of patients. Amisulpride should be used with caution in patients with risk factors for stroke.
In elderly patients with psychosis associated with dementia, for the treatment of antipsychotic drugs was observed increase in the risk of death. An analysis of 17 placebo-controlled studies (mean duration of more than 10 weeks), conducted primarily in patients treated with atypical antipsychotic drugs, revealed that they had a 1.6-1.7 times greater risk of death than patients treated with placebo. Although the causes of death in clinical trials with atypical antipsychotics were varied, most of the causes of death were cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to the treatment of atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The degree to which an increase in mortality may be due to antipsychotic rather than some features of patients is not clear.
cases of "lifting" syndrome has been described In a dramatic admission of high therapeutic doses of neuroleptics. When receiving amisulpride reported occurrence of involuntary movement disorders such as akathisia, a violation of muscle tone and dyskinesia. Therefore, we recommend a gradual reduction in dose when canceling amisulpride.
In the application of neuroleptics, including Solian, reported on the development of leukopenia, neutropenia, agranulocytosis. Do not have an explanation infection or fever mogug be associated with hematological disorders and hematological require immediate investigation.
In the application of antipsychotic drugs have been cases of venous thromboembolism, sometimes with fatal consequences. Therefore amisulpride should be used with caution in patients with risk factors for thromboembolism.
Withdrawal amisulpride carried kidneys. If the kidney function dose should decrease.
Effects on ability to drive vehicles and management mechanisms
It is necessary to inform patients in particular are drivers of vehicles or persons working with machinery, the possibility of the appearance of their sleepiness and decrease psychomotor reactions while taking amisulpride, especially early in treatment, as it can be dangerous when driving and operating machinery .
Storage conditions
Store at temperatures not above 25 ° C.
Shelf life: 3 years.
Keep out of the reach of children.
Do not use after the expiration date.
