Солиан®

General characteristics. Structure:

Active agent: амисульприд — 10,0 g;
excipients: Acidum hydrochloricum solution - to рН = 4,5-6,5 (about 8,4 ml), methylparahydroxybenzoate - 0,1 g, пропилпарагидроксибензоат-0,05 g, potassium sorbate - 0,2 g, fragrance caramel - 1,0 g, water - to 100 ml Gesvit ® * 4 g, 3 M. * — Gesvit ® contains sodium saccharinate (75 - 85%), глюкуролактон (15 - 20%), sodium a gluconate (<5%).
Description: transparent liquid from yellow till brownish-yellow color with a caramel smell.

Pharmacological properties:

Pharmacodynamics. Amisulprid is antipsychotic drug from group of the replaced benzamides. The Pharmakodinamichesky profile of an amisulprid is caused by the selection and preferential affinity to the D2 and D3 subtypes of dopamine receptors of limbic system. Amisulprid has no affinity to serotoninovy and other neuroceptors, such as histamine, cholinergic and adrenergic receptors.
In researches on animals it was shown what at reception in high doses амисульприд more blocks dofaminergichesky neurons of mesolimbic system, than similar neurons in system of a striatum. Dominance of antipsychotic effects of an amisulprid over its extrapyramidal effects is explained by this specific affinity, apparently.
At use in low doses амисульприд preferential blocks presynaptic D2 and D3 dopamine receptors, than its positive influence on negative symptoms can speak.
According to a controlled double-blind research on comparison of an amisulprid and a haloperidol at patients with acute schizophrenia (191 patients) at use of an amisulprid authentically bigger reduction of secondary negative symptoms was observed. According to clinical trials at use of an amisulprid authentically smaller frequency of emergence of extrapyramidal symptoms was observed, than at use of a haloperidol.

Pharmacokinetics. At an amisulprid two absorbing peaks are noted: one is reached quickly, in an hour, and the second - between the 3 and 4 hour after administration of drug. The corresponding concentration in plasma after administration of drug in a dose of 50 mg make 39±3 ng/ml and 54±4 ng/ml, respectively.
The volume of distribution is equal to 5,8 l/kg. Due to the low communication with proteins of plasma (16%), interaction of an amisulprid with other drugs at the level of communication with protein is not expected. Absolute bioavailability makes 48%.
Amisulprid is slightly metabolized in a liver (about 4%), two inactive metabolites are identified. At course reception of accumulation of an amisulprid does not occur, and its pharmacokinetics does not change. At intake the elimination half-life (T1/2) of an amisulprid makes about 12 hours. Amisulprid is brought with urine in not changed look. The renal clearance makes about 330 ml/min.
Carbohydrate-rich food authentically reduces AUC (the area under a curve "concentration/time"), time of achievement of the maximum concentration in a blood plasma (Tmax) and maximum concentration of an amisulprid in a blood plasma (Cmax) while food of changes of the above-stated pharmacokinetic indicators rich with fats does not cause. However value of these observations in daily clinical practice is unknown.
Renal failure
The elimination half-life at patients with a renal failure does not change, but the system clearance decreases by 2,5 - 3 times. AUC of an amisulprid at a renal failure of easy degree increases twice, and at a renal failure of moderate severity - is almost tenfold (see the section "Route of Administration and Doses"). Experience of use of drug at a renal failure is limited, and there are no data on reception of an amisulprid in the dose exceeding 50 mg. Amisulprid is practically not brought by means of a hemodialysis. Liver failure
Because амисульприд it is slightly metabolized in a liver, at a liver failure of accumulation of drug it is not expected, and decrease in its doses is not required. Patients of advanced age
When comparing pharmacokinetic indicators of patients 65 years with those at patients of younger age are more senior it is established that at them after a single dose in an amisulprid in a dose of 50 mg of Cmax, T1/2 and AUC value is 10-30% higher. Data on pharmacokinetics indicators at patients of advanced age at course reception of an amisulprid are absent.

Indications to use:

Schizophrenia: acute or chronic schizophrenic frustration with productive symptomatology  (nonsense, hallucinations, disorders of thinking) and/or negative symptomatology (affect flattening, loss of emotional and social relateds), including patients with dominance of negative symptomatology.

Route of administration and doses:

Drug is intended for intake.
To open a bottle with the "protection against children" device it is necessary to press on a cover of a bottle and to turn it. The appointed dose is gathered by means of the syringe (1 ml contains 100 mg of an amisulprid).
Usually, if the daily dose does not exceed 400 mg, it can be accepted once a day if the daily dose exceeds 400 mg, then it has to be divided into two receptions. At dominance of negative symptomatology
For patients with dominance of negative symptomatology purpose of an amisulprid in a dose from 50 to 300 mg a day is recommended (on average in a dose of 100 mg a day). Selection of a dose has to be carried out individually.
At the mixed episodes with productive and negative symptomatology
For patients with mixed (negative and productive) symptoms of a dose follows
to select so that to provide optimum control over productive symptoms, in
average they make from 400 mg to 800 mg. The supporting treatment has to
to be established individually at the level of minimal effective doses (depending on
reactions of the patient).
Acute psychotic episodes
Initiation of treatment:
- it is possible to begin treatment by intramuscular administration of drug within several days in the maximum dose of 400 mg/day with the subsequent transition to administration of drug inside.
- doses from 400 to 800 mg are applied to intake. The maximum dose never has to exceed 1200 mg a day.
Maintenance therapy
Afterwards, the picked-up dose remains or adjusted depending on reaction of the patient. In all cases maintenance doses have to be established individually at the level of minimum effective doses. At patients with a renal failure
Clinical experience of use of drug for patients with renal failures is limited. Removal of an amisulprid is carried out through kidneys. At a renal failure the dose for patients with clearance of creatinine of 30 - 60 ml/min. should be reduced half, and for patients with clearance of creatinine from 10 to 30 ml/min. - three times.
Due to the lack of data on use of drug for patients with clearance of creatinine   less than 10 ml/min., use of an amisulprid for this group of patients are contraindicated (see the section "Contraindications"). At patients with a liver failure
Because drug is poorly metabolized in a liver, decrease in its dose at a liver failure is not required. At children
Efficiency and safety of reception of an amisulprid at children and teenagers up to 18 years are not established. There are limited data on use of an amisulprid for teenagers at schizophrenia. At children and teenagers up to 18 years use of an amisulprid is contraindicated (see the section "Contraindications").

Features of use:

As well as at use of other neuroleptics, at use of an amisulprid (especially high doses) the malignant antipsychotic syndrome, potentially lethal complication which is characterized by the hyperthermia, muscle tension, vegetative frustration raised by concentration of a kreatinfosfokinaza in blood can develop. At development of a hyperthermia, especially against the background of use of high doses of neuroleptics, all antipsychotic drugs, including амисульприд, have to be cancelled. It is necessary to be careful at purpose of blockers of dopamine receptors and in particular an amisulprida at Parkinson's disease as at his appointment deterioration in a course of this disease is possible. At patients with Parkinson's disease амисульприд it is necessary to apply only if it is impossible to avoid its use. If the patient with Parkinson's disease receiving agonists of dopamine receptors needs treatment amisulpridy, then agonists of dopamine receptors should be cancelled gradually (by a gradual dose decline before their full cancellation) as sharp cancellation can lead to development of a malignant antipsychotic syndrome. For correction of the extrapyramidal symptoms which arose against the background of treatment amisulpridy it is necessary  to use  anticholinergic  protivoparkinsonichesky  drugs  (but  not agonists of dopamine receptors).
Because амисульприд causes dozozavisimy increase in duration of an interval at its reception the risk of development of Bouveret's diseases, including potentially life-threatening ventricular tachycardia like "pirouette" (torsade des pointes) increases. Therefore if the condition of the patient allows, before purpose of an amisulprid it is recommended to remove an ECG and to investigate electrolytic composition of blood, to reveal and whenever possible to correct factors which can promote emergence of such dangerous disturbances of a rhythm (such as bradycardia less than 55 beats per minute; hypopotassemia; hypomagnesiemia; the inborn or acquired lengthening of an interval of QT; a concomitant use of the drugs capable to cause the expressed bradycardia (less than 55 уд. / mines), a hypopotassemia, delay of endocardiac conductivity to increase QT interval duration) (see the section "Interaction with Other Medicines"). During treatment amisulpridy it is impossible to accept alcohol and drugs containing alcohol.
Owing to ability of drug to lower a threshold of convulsive readiness, at reception of an amisulprid by patients with epilepsy behind them it is necessary to carry out careful clinical and, whenever possible, elektroentsefalografichesky observation.
Some atypical neuroleptics, including амисульприд, can cause increase in level of sugar in blood. At patients with a diabetes mellitus and patients with risk factors of development of a diabetes mellitus at purpose of an amisulprid it is regularly necessary to control sugar level in blood.
At patients of advanced age амисульприд, as well as other neuroleptics, it is necessary to apply with extra care because of possible risk of a lowering of arterial pressure or development of excessive sedation.
In the randomized clinical trials conducted at group of the elderly patients with dementia receiving treatment by some atipichesky antipsychotic drugs triple increase in risk of development of cerebrovascular complications in comparison with placebo reception was observed. The mechanism of such increase in risk is unknown. It is impossible to exclude increase in such risk at use of other antipsychotic drugs or for other groups of patients. Amisulprid has to be applied with care at patients with risk factors of development of a stroke. At patients of advanced age with the psychoses connected with dementia at treatment antipsychotic drugs observed increase in risk of approach of death. The analysis of 17 placebos - the controlled researches (with an average duration more than 10 weeks) conducted main in the way, at the patients receiving atipichesky antipsychotic drugs showed that they had 1,6-1,7 times bigger risk of death, than for the patients receiving placebo. Though causes of death in clinical trials with atipichesky antipsychotic drugs varied, the majority of the reasons of death had cardiovascular (for example, heart failure, sudden death), or infectious (for example, pneumonia) the nature. The observation researches confirmed that it is similar to treatment by atipichesky antipsychotic drugs, treatment by usual antipsychotic drugs can also increase mortality. Degree to which increase in mortality can be caused by antipsychotic drug, but not some features of patients is not clear.
At the sharp termination of reception of high therapeutic doses of neuroleptics cases of development of a syndrome of "cancellation" were described. At reception of an amisulprid it was reported about emergence of involuntary motive frustration, such as an akathisia, disturbance of a muscle tone and dyskinesia. Therefore gradual decrease in doses at cancellation of an amisulprid is recommended.
At use of neuroleptics, including Solian®, it was reported about development of a leukopenia, neutropenia, agranulocytosis. Not having explanations of an infection or fever can be connected with hematologic disturbances (see the section "Side effect") and demand immediate hematologic inspection.
At use of antipsychotic drugs cases of a venous thromboembolism, sometimes with a lethal outcome were observed. Therefore амисульприд it is necessary to apply with care at patients with risk factors of development of a thromboembolism.
Removal of an amisulprid is carried out by kidneys. At a renal failure of a dose of drug have to decrease (see the section "Route of Administration and Doses").
Influence on ability to manage vehicles or other mechanisms
It is necessary to inform the patients who are especially drivers of vehicles or persons, working with mechanisms on a possibility of emergence at them of drowsiness and decrease in psychomotor reactions during reception of an amisulprid, especially in an initiation of treatment as it can be dangerous at control of vehicles and work with mechanisms.

Side effects:

Side effects are presented according to the following gradation of frequency of their emergence: very frequent (> 10%), frequent (> 1%, <10%); infrequent (> 0,1%, <1%); rare (> 0,01%, <0,1%) and very rare, including separate messages (<0,01%), unknown frequency (it is not possible to determine the frequency of occurrence of undesirable effects by the available data).
The side effects observed in controlled clinical trials and at post-marketing use of drug are listed below. It should be noted that it is in certain cases very difficult to otdifferentsirovat side effects from symptoms of a basic disease.
Disturbances from the central nervous system
Very frequent
Extrapyramidal symptoms (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia). These symptoms usually happen moderately expressed at reception in optimum doses and  partially reversible at addition anticholinergic
protivoparkinsonichesky drugs without the treatment termination amisulpridy. Frequency of emergence of extrapyramidal symptoms depends on a dose. Therefore at the patients with preferential negative symptoms accepting амисульприд in a dose of 50-300 mg, the frequency of emergence of extrapyramidal frustration is very low. According to clinical trials at use of an amisulprid authentically smaller frequency of emergence of extrapyramidal symptoms was observed, than at use of a haloperidol. Frequent
Acute dystonias (spastic wryneck, okulogirny crises, lockjaw), reversible at addition of anticholinergic protivoparkinsonichesky drugs without the treatment termination amisulpridy. Day drowsiness. Infrequent
Late dyskinesia characterized by the rhythmical, involuntary movements preferential of language, and/or face muscles, arising usually after long administration of drug. Anticholinergic protivoparkinsonichesky drugs in these cases are not effective or can strengthen symptomatology. Attacks of spasms. Unknown frequency
Malignant antipsychotic syndrome (see the section "Special Instructions") which is potentially lethal complication. Disturbances from mentality
Frequent
Sleeplessness, feeling of alarm, agitation, disturbances of an orgasm. Disturbances from a digestive tract
Frequent
Lock, nausea, vomiting, dryness in a mouth. Disturbances from endocrine system
Frequent
Amisulprid causes increase in plasma concentration of prolactin, reversible after  drug withdrawal.  It  can lead  to emergence  of a galactorrhoea,  amenorrhea, gynecomastia, mammary gland pains and erectile dysfunction. Metabolic disturbances
Frequent
Increase in body weight. Infrequent
Hyperglycemia (see the sections "With Care" and "Special Instructions"). Disturbances from cardiovascular system
Frequent
Lowering of arterial pressure.
Infrequent
Bradycardia.
Unknown frequency
Lengthening of an interval of QT; ventricular disturbances of a rhythm, such as polymorphic ventricular tachycardia like "pirouette" (torsade des pointes) which can turn into fibrillation of ventricles and lead to a cardiac standstill and sudden death (see the section "Special Instructions").
Thromboembolisms, including a thromboembolism of a pulmonary artery, sometimes with a lethal outcome, and a deep vein thrombosis (see the section "Special Instructions"). Disturbances from laboratory indicators
Infrequent
Increase in activity of "hepatic" enzymes, mainly transaminases in blood.
Disturbances from immune system
Infrequent
Allergic reactions.

Unknown frequency
Quincke's disease and small tortoiseshell.
Disturbances from blood and lymphatic system
Unknown frequency
Leukopenia, neutropenia and agranulocytosis (see the section "Special Instructions").
Pregnancy, puerperal and perinatal states
Unknown frequency
Syndrome of "cancellation" at newborns.

Interaction with other medicines:

Contraindicated combinations
- With the drugs capable to extend an interval of QT and to cause Bouveret's diseases, including potentially lethal polymorphic ventricular tachycardia like "pirouette" (torsade des pointes):
- with antiarrhytmic drugs 1A of a class (quinidine, Disopyramidum) and the III class (Amiodaronum, соталол, дофетилид, ибутилид);
- with bepridily, tsizapridy, methadone, sultopridy, thioridazine, difemanit methyl sulfate, erythromycin (intravenously), Spheromycinum (intravenously), mizolastiny, Vincaminum (intravenously), galofantriny, lumefantriny, sparfloksatsiny, gatifloksatsiny, moksifloksatsiny, pentamidine, etc.
The risk of development of Bouveret's diseases, including potentially lethal ventricular tachycardia like "pirouette" (torsade des pointes) increases (see the section "Contraindications"):
- With agonists of dopamine receptors (каберголин, хинаголид)
Mutual antagonism of effects of agonists of dopamine receptors and neuroleptics. Agonists of dopamine receptors can cause or strengthen psychotic symptomatology (see the section "Special Instructions").
- With a levodopa (watch "Contraindications").
Reciprocal antagonism of effects levodopa and neuroleptics. Not recommended combinations
With the drugs increasing risk of developing of potentially lethal ventricular tachycardia like "pirouette" ("torsade despointes")
- with the drugs causing bradycardia (beta adrenoblockers, verapamil, diltiazem, a clonidine, гуанфацин, digitalis drugs, donepezil, ривастигмин, такрин, an ambenoniya chloride, Galantaminum, pyridostigmine bromide, a neostigmin bromide);
- with the drugs causing a hypopotassemia (with the diuretics simulating an intestines peristaltics laxatives, intravenously entered Amphotericinum In, glucocorticosteroids, tetrakozaktida causing a hypopotassemia) - at their use it is necessary to recover surely losses of potassium and to support the normal level of potassium in blood;
- c some neuroleptics (haloperidol, Pimozidum, pipotiaziny, sertindoly, Chlorpromazinum, levomepromazinum, tsiamemaziny, sultopridy, Sulpiridum, tiapridy, veralipridy, Droperidolum), imipraminovy antidepressants, lithium drugs, azolny antifungal drugs.
The risk of development of ventricular arrhythmias increases, in particular ventricular tachycardia of type "feasts" ("torsade des pointes").
- With alcohol
Amisulprid strengthens the central effects of alcohol. Alcohol strengthens sedative action of neuroleptics.
- With agonists of dopamine receptors (амантадин, Apomorphinum, Bromocriptinum, энтакапон, лисурид, перголид, piribedit, прамипексол, ропинирол, селегилин) (see the section "Special Instructions"),
Mutual antagonism of effects of agonists of dopamine receptors and neuroleptics. Agonists of dopamine receptors can cause or strengthen psychotic symptomatology. Amisulprid can strengthen symptoms of a disease of Parkinson. Combinations which should be taken into account
- With drugs, the oppressing TsNS: morphine derivatives (analgetics, antibechic drugs); barbiturates; benzodiazepines; not benzodiazepine anxiolytics; somnolent drugs; antidepressants with sedation (amitriptyline, доксепин, миансерин, миртазапин, тримипрамин); Hl-gistaminoblokatorami with sedation; hypotensive drugs of the central action (clonidine); neuroleptics; Baclofenum; thalidomide, pizotifeny.
The expressed strengthening of the oppressing action on TsNS. Additional decrease in concentration of attention that creates big danger to the drivers of transport and faces working with mechanisms.
- With hypotensive drugs, including beta adrenoblockers (бисопролол, карведилол, метопролол)
Risk of development of hypotension, in particular orthostatic hypotension (additive effect). Concerning beta adrenoblockers in addition see  the section "Interaction with Other Medicines", the subsection "Not Recommended Combinations".

Contraindications:

- Hypersensitivity to an amisulprid or to other components of drug.
- The accompanying prolaktinzavisimy tumors, for example: prolaktinoma of a hypophysis and breast cancer.
- The diagnosed pheochromocytoma, suspicion on a pheochromocytoma.
- Children's and teenage age up to 18 years (lack of clinical experience of use).
- Feeding period breast.
- A heavy renal failure with clearance of creatinine less than 10 ml/min. (lack of clinical experience).
- The accompanying therapy kabergoliny, hinagolidy (see the section "Interaction with Other Medicines").
- The accompanying therapy a levodopa (see the section "Interaction with Other Medicines").
- The accompanying therapy by the drugs capable to extend an interval of QT and to cause development of disturbances of a rhythm, including potentially life-threatening ventricular tachycardia like "pirouette" (torsade des pointes) (see the section "Interaction with Other Medicines"):

- antiarrhytmic drugs! Class A (quinidine, Disopyramidum) and III class (Amiodaronum, соталол, дофетилид, ибутилид);
- other medicines (bepridit, цизаприд, methadone, сультоприд, thioridazine, difemanit the methyl sulfate entered intravenously erythromycin, entered intravenously Spheromycinum, мизоластин, entered intravenously Vincaminum, галофантрин, лумефантрин, спарфлоксацин, moxifloxacin, pentamidine, etc. (see the section "Interaction with Other Medicines").
With care
- Patients with the contributing factors have development of heavy ventricular arrhythmias, including potentially life-threatening ventricular tachycardia like "pirouette" (torsade des pointes) (амисульприд it is capable дозозависимо to extend an interval of QT and to increase risk of development of heavy ventricular arrhythmias, including ventricular tachycardia like "pirouette" (torsade des pointes) (see the sections "Side Effect", "Interaction with Other Medicines"):
- patients with the inborn extended interval have QT;
- patients with the acquired lengthening of an interval have QT (at a combination with the drugs increasing QTc-interval duration except for specified in the section "Contraindications", see the section "Interaction with Other Medicines");
- patients with bradycardia have less than 55 beats per minute;
- at patients with electrolytic frustration, including a hypopotassemia;
- at the patients receiving the accompanying therapy by the drugs capable to cause a hypopotassemia, the expressed bradycardia less than 55 beats per minute to slow down endocardiac conductivity.
- At patients with a renal failure as there is a risk of cumulation of drug, and experience of its use at a renal failure is limited (see the sections "Pharmacokinetics", "Dosing Mode", "Special Instructions").
- At patients of advanced age as they have an increased predisposition to a lowering of arterial pressure and development of excessive sedation.
- At patients of advanced age with dementia (see the section "Special Instructions").
- Patients with risk factors have development of a stroke (see the section "Special Instructions").
- At patients with epilepsy as амисульприд can reduce a threshold of convulsive readiness.
- Patients with risk factors have development of thromboembolisms (watch "Side effect", "Special instructions").
- At patients with Parkinson's disease as амисульприд, as well as other antidofaminergichesky drugs, can strengthen displays of a disease of Parkinson (watch "Special instructions").
- At patients with a diabetes mellitus and patients with risk factors of development of a diabetes mellitus (as some atypical neuroleptics, including амисульприд, can cause increase in level of sugar in blood).
Pregnancy and lactation
Safety of reception of an amisulprid during pregnancy is not established. Therefore use of drug at pregnancy is not recommended unless the expected advantage for mother justifies potential risk for a fruit. The newborns who were exposed during the third trimester of pregnancy to pre-natal influence of neuroleptics including Solian®, have risk of development of undesirable reactions, including an extrapyramidal syndrome or a syndrome of "cancellation" which can vary on weight and duration after the delivery (see the section "Side effect"). It was reported about development of excitement, a muscle hyper tone, tremor, drowsiness, respiratory frustration or disturbances when feeding. Therefore such newborns need careful observation of their state.
It is not known whether it is capable амисульприд to get into maternal milk therefore feeding
breast during its reception contraindicated.

Overdose:

Symptoms
The experience connected with overdose of an amisulprid is very limited. It was reported about considerable strengthening of the known pharmacological effects of drug, namely about development of drowsiness, sedation, a lowering of arterial pressure, extrapyramidal symptoms and a coma. There were messages on deaths at overdose, mainly, at a combination with other psychotropic drugs. It must be kept in mind that the phenomena of overdose can arise in cases of wrong reception of additional doses of drug or a concomitant use of other drugs. Treatment
There is no specific antidote for an amisulprid.
In case of overdose it is necessary to control and support the main vital functions of an organism up to a full exit of the patient from a condition of overdose. At overdose carrying out ECG monitoring is obligatory as there is a risk of lengthening of an interval of QT and development of life-threatening disturbances of a rhythm (see the section "Side effect").
In case of heavy extrapyramidal symptoms, it is necessary to apply m-holinoblokatory of the central action, for example, trigeksifenidit.
As removal of an amisulprid by means of a hemodialysis is insignificant, for its removal at overdose use of a hemodialysis is inexpedient.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years.
Not to use drug after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intake of 100 mg/ml.
On 60 ml in the bottle of light-protective glass (type III) corked by a cover with protection against opening by children.
On 1 bottle together with the dosing syringe and the application instruction in a cardboard pack.