Soleron

General characteristics. Structure:

Active agent: amisulprida of 100 mg or 200 mg;

Excipients: lactoses monohydrate, cellulose microcrystallic, gidroksipropilmetiltsellyuloza, sodium of a kroskarmeloz, silicon dioxide colloid anhydrous, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Soleron is the antipsychotic means belonging to the class of the replaced benzamides. Amisulprid selectively, with high affinity contacts the D2/D3 subtypes of dofaminergichesky receptors. Amisulprid has no affinity with receptors of serotonin, a histamine, adrenergic and cholinergic receptors.
At use in high doses blocks preferential dofaminergichesky neurons which are localized in mesolimbic structures, but not in striatal system. This specific affinity explains preferential antipsychotic action of an amisulprid.
In low doses it preferential blocks presynaptic D2-/D3-receptors that explains its action on negative symptoms of schizophrenia.
In controlled (with a haloperidol) double blind clinical trial with participation of patients with acute schizophrenia амисульприд authentically reduced expressiveness of secondary negative symptoms of a disease in much bigger degree, than a haloperidol.
After Soleron's reception two absorbing peaks are inside noted: one is reached quickly, in an hour after reception, and the second - between the 3rd and 4th for hours after reception. Concentration in a blood plasma makes respectively 39±3 and 54±4 ng/ml after reception in a dose of 50 mg.
The volume of distribution makes 5,8 l/kg. As linkng with proteins of a blood plasma low (16%), interaction with other drugs is improbable.

Pharmacokinetics. Absolute bioavailability makes 48%. Amisulprid is poorly metabolized in an organism: two of its are identified inactive a metabolite, the making about 4% of the entered dose.
Cumulation of an amisulprid does not happen, its pharmacokinetics remains invariable after repeated receptions. The elimination half-life of an amisulprid after oral administration makes about 12 h.
Amisulprid is brought in not changed view with urine. Later in/in introductions of 50% of a dose it is allocated with urine, and 90% of this quantity are removed during the first 24 h. The renal clearance makes about 20 l/hour, or 330 ml/min.
The carbohydrate-rich food (containing 68% of liquid) authentically reduces AUC (the area under a curve concentration/time), Tmaxmax (the maximum concentration) of an amisulprid in blood. After reception of greasy food of similar changes it is noted.
Because амисульприд poorly is exposed to metabolism, patients have no need for decrease in its dose with an abnormal liver function.
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 slightly expressed renal failure increases twice, and at moderately expressed renal failure - is almost tenfold. The practical experience of use of drug, however, is limited, and there are no results on use of drug in the doses exceeding 50 mg.
Amisulprid poorly is exposed to dialysis.

Indications to use:

The psychoses, especially acute and chronic schizophrenic disorders which are followed by positive symptoms (for example, nonsense, hallucinations, disorders of thinking) and/or negative symptoms (for example, affective dullness, lack of emotionality and evasion from communication), including at patients with dominance of negative symptoms.

Route of administration and doses:

Apply to adults and children 15 years inside, irrespective of meal are more senior. It is necessary to swallow of a tablet without chewing, washing down with enough water.

If the daily dose does not exceed 400 mg, Soleron it is necessary to accept once a day. The dose more than 400 mg should be distributed on 2 receptions.
Patients with preferential negative symptoms are recommended to appoint drug in a dose from 50 (1/2 tablets of 100 mg) to 300 mg a day. Selection of a dose has to be individual. The optimum dose makes about 100 mg a day.

For patients with the mixed negative and positive symptoms of a dose it is necessary to select so that to provide the maximum control over positive symptoms, i.e. 400 - 800 mg a day. The supporting treatment is carried out in minimum effective dose which is established individually.

At acute psychotic episodes the recommended initial dose makes 400 - 800 mg, the maximum daily dose - no more than 1200 mg. The supporting treatment is carried out in minimum effective dose which is established individually.

Renal failure. As removal of an amisulprid is carried out by kidneys, at a renal failure at patients with clearance of creatinine of 30 - 60 ml/min. the daily dose should be lowered half, and patients with clearance of creatinine have 10 - 30 ml/min. - to one third.

As drug is poorly metabolized in an organism, decrease in its dose at an abnormal liver function is not required. 

Considerable part of patients with schizophrenic disturbances is forced to accept drug constantly to avoid aggravations. The treatment duration, selection of a dose and size of a maintenance dose are established individually.

Features of use:

Use during pregnancy or feeding by a breast.
Soleron's safety during pregnancy is not established therefore use of drug is not recommended.
It is unknown whether gets амисульприд into breast milk therefore feeding by a breast contraindicated. 

Children. Safety and efficiency of use of drug for treatment of children up to 15 years is not established.

Soleron it is necessary to apply only if it is impossible to avoid antipsychotic therapy.

As well as when using other neuroleptics, at treatment by Soleron development of the malignant antipsychotic syndrome which is characterized by a hyperthermia, muscle tension, dysfunction of a peripheral nervous system, the increased kreatinfosfokinaza level in blood serum is possible. At development of a hyperthermia, especially at use in high doses, all antipsychotic drugs, including Soleron, have to be cancelled.

Soleron can cause dozozavisimy increase in an interval of QT at an ECG that increases risk of emergence of dangerous ventricular tachyarrhythmias like blinking trembling of ventricles. The risk of development of dangerous ventricular arrhythmias increases at bradycardia, a hypopotassemia, in case of the inborn or acquired syndrome of the extended QT interval (a combination with the drugs extending QT interval).

If the clinical situation allows, then before use of drug it is recommended to be convinced of lack of factors which can promote development of this disturbance of a rhythm: bradycardia of less than 55 уд. / mines, a hypopotassemia, the inborn extended QT interval, simultaneous use of the drugs capable to cause the expressed bradycardia (<55 уд. / mines), a hypopotassemia, delay of endocardiac conductivity or increase in an interval of QT. Patients who need prolonged treatment by neuroleptics before their appointment are recommended to conduct an ECG research.

Soleron can reduce a convulsive threshold. Therefore medical observation of the patients accepting Soleron with spasms in the anamnesis is necessary.

At patients of advanced age Soleron as well as other neuroleptics, it is necessary to apply with extra care because of possible risk of development of arterial hypotension or sedation.

It is necessary to apply with extra care Soleron at Parkinson's disease.

Drug contains lactose therefore it is not recommended for use by the patient with insufficiency of lactase, a galactosemia or a syndrome of disturbance of absorption of glucose or a galactose.

Ability to influence speed of reactions at control of motor transport or other mechanisms.
Drug can cause drowsiness therefore ability to control of vehicles or work with dangerous mechanisms can be broken.

Side effects:

From a nervous system:
often - sleeplessness, alarm, agitation, extrapyramidal symptoms (a tremor, arterial hypertension, hypersalivation, an akathisia, a hypokinesia). Expressiveness of these symptoms usually moderate, they are partially reversible without Soleron's cancellation at purpose of anticholinergic antiparkinsonichesky therapy. Frequency of development of extrapyramidal symptoms depends on a dose of drug and very low at the patients accepting drug in a dose of 50 - 300 mg/days for elimination of preferential negative symptoms;
seldom - day drowsiness;
very seldom - the acute dystonia (a spastic wryneck, okulogirny crisis, a lockjaw) which is not demanding Soleron's cancellation and passing at use of anticholinergic protivoparkinsonichesky means; the late dyskinesia which is characterized by the involuntary movements preferential of language and/or mimic face muscles develops usually at prolonged use of drug (anticholinergic antiparkinsonichesky cure for it are inefficient, they can cause an aggravation of symptoms); spasms; malignant antipsychotic syndrome.

Endocrine disturbances: often - reversible increase in level of prolactin in blood serum (passing after drug withdrawal) which can cause a galactorrhoea, an amenorrhea, a gynecomastia, swelling of mammary glands, impotence and frigidity; increase in body weight.

From  digestive tract: seldom - a lock, nausea, vomiting, dryness in a mouth.

From cardiovascular system: very seldom - arterial hypotension and bradycardia, increase in an interval of QT at an ECG; in isolated cases - a ventricular tachyarrhythmia as blinking trembling.

From gepatobiliarny system: very seldom - increase in activity of enzymes of a liver, especially transaminases.

From immune system: very seldom - allergic reactions.

Interaction with other medicines:

Contraindicated combinations.
Agonists of dofaminergichesky receptors, except a levodopa (амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол, селегилин), - except for use for patients with Parkinson's disease. Agonists of dofaminergichesky receptors and neuroleptics are mutual antagonists. At the extrapyramidal syndrome caused by neuroleptics instead of agonists of dofaminergichesky receptors use of anticholinergic drugs is recommended.

Sultoprid (benzamide neuroleptic) - increase in risk of development of ventricular arrhythmias, especially tachyarrhythmias as blinking trembling.

Not recommended combinations.
Medicines which can cause a tachyarrhythmia as blinking trembling: the antiarrhytmic drugs Ia of a class (quinidine, hydroquinidine, Disopyramidum) and the III class (Amiodaronum, соталол, дофетилид, ибутилид), some neuroleptics (thioridazine, Chlorpromazinum, levomepromazinum, трифлуоперазин, циамемазин, Sulpiridum, тиаприд, Pimozidum, a haloperidol, Droperidolum) and other drugs, such as bepridit, цисаприд, difemanit, intravenous erythromycin, мизоластин, intravenous Vincaminum, галофантрин, спарфлоксацин, гатифлоксацин, moxifloxacin, pentamidine, intravenous Spheromycinum - increase in risk of development of ventricular arrhythmias, especially tachyarrhythmias as blinking trembling. Whenever possible it is necessary to cancel such drugs; if the similar combination of drugs does not manage to be avoided, prior to treatment it is necessary to determine QT interval duration on an ECG, to carry out treatment under control of an ECG.

Alcohol - strengthening of sedation of neuroleptics and decrease in vigilance. It is necessary to avoid alcohol intake and use of the medicines containing alcohol during treatment by Soleron.

Levodopa - mutual antagonism of action of a levodopa and neuroleptics. For treatment of patients with Parkinson's disease both drugs are recommended to be used in minimal effective doses.

Agonists of dofaminergichesky receptors, except a levodopa (амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол, селегилин) - which are used for treatment of patients with Parkinson's disease. Dofaminergichesky agonists are mutual antagonists with neuroleptics. Agonists of dofaminergichesky receptors can cause or strengthen psychotic disturbances. If treatment by neuroleptics is necessary for the patient with Parkinson's disease accepting dofaminergichesky drug, its dose should be lowered gradually to full cancellation (sharp cancellation can lead to development of a malignant antipsychotic syndrome).

The combinations demanding care of use.
The drugs causing bradycardia (blockers of calcium channels: diltiazem, verapamil; blockers of β-receptors, except a sotalol; clonidine, гуанфацин; мефлохин; foxglove drugs, cholinesterase inhibitors: donezpepzit, ривастигмин, такрин, амбемониум, галаитамин, pyridostigmine, неостигмин), increase risk of emergence of ventricular arrhythmias, in particular blinking trembling tachyarrhythmias. Also ECG control is necessary clinical.

Drugs which can cause a hypopotassemia: the kaliyvyvodyashchy diuretics stimulating laxatives, intravenous Amphotericinum In glucocorticoids, тетракосактид, increase risk of emergence of ventricular arrhythmias, in particular blinking trembling tachyarrhythmias.

The hypopotassemia needs to be corrected prior to drug use. Control of electrolytic balance, an ECG, condition of the patient is necessary.

Combinations which should be taken into account.
Anti-hypertensive drugs (all) - the additive action, increase in risk of development of postural hypotension.

The other means having the oppressing effect on TsNS: morphine derivatives, barbiturates, benzodiazepines and other anxiolytics, somnolent drugs, antidepressants with sedative action (amitriptyline, доксепин, миансерин, миртазапин, тримипрамин), H1 receptors blockers with sedative action, anti-hypertensive central acting agents, neuroleptics, Baclofenum, a thalidomide, пизотифен - strengthening of the central depression, decrease in attention and speed of reaction.

Beta-blockers at heart failure: бисопролол, карведилол, метопролол - vasodilating action, risk of development of arterial hypotension, especially orthostatic (the additive effect).

Contraindications:

Hypersensitivity to active ingredient or other components of drug. The diagnosed or estimated pheochromocytoma. The diagnosed or estimated prolaktinzavisimy tumors (for example, a prolaktinoma of a hypophysis and a breast cancer). Heavy renal failure (clearance of creatinine <10 ml/min.). Simultaneous use with sultopridy and agonists of dofaminergichesky receptors, such as амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол, селегилин, except for patients with Parkinson's disease (see the section "Interaction with Other Medicines and Other Types of Interactions"). An inborn galactosemia, a syndrome of disturbance of absorption of glucose or a galactose, deficit of lactase (because of contents as a part of lactose drug). Pregnancy. Feeding period breast. Children's age up to 15 years (in view of lack of clinical data).

Overdose:

Strengthening of the known pharmacological effects of drug, such as drowsiness, sedation, arterial hypotension, extrapyramidal symptoms is possible; coma. There is no specific antidote.

At acute overdose the maintenance therapy, monitoring of the vital functions of an organism, especially control of an ECG before full normalization of a condition of the patient is shown. At emergence of the expressed extrapyramidal symptoms appoint anticholinergics. The hemodialysis is inefficient.

Storage conditions:

To store in original packaging, in the place, unavailable to children, at a temperature not over 25 ˚С.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in blisters; on 1 or 3 blisters in packs cardboard.