Prosulpin

General characteristics. Structure:

Active agent: 200 mg; 50 mg of Sulpiridum.

Pharmacological properties:

Pharmacodynamics. Sulpiridum - an atypical neuroleptic from group of the replaced benzamides. Has moderate antipsychotic activity in a combination to the stimulating and timoanaleptichesky (antidepressive) action.
The antipsychotic effect is connected with anti-dopaminergic action. Blocks dopaminergic D2-and D3 receptors, influences neostriatny system slightly, possesses antipsychotic action. Antipsychotic action of Sulpiridum is shown in doses more than 600 mg/, in doses to 600 mg / the stimulating and antidepressive action prevails.
Sulpiridum does not make considerable impact on норадренергическис, atsetilkholinovy, serotoninovy, histamine and GABA receptors.
In small doses Sulpiridum can be applied as supportive application at treatment of psychosomatic diseases, in particular, of a peptic ulcer of a stomach and a duodenum. At an irritable colon reduces intensity of abdominal pains.
Low doses of Sulpiridum (50-300 mg/) are effective at dizzinesses.
Stimulates secretion of prolactin and has the central antiemetichesky effect (oppression of the emetic center).

Pharmacokinetics. At appointment in Cmax in a blood plasma it is reached in 3–6 h and makes 0,73 mg/l at reception of one tablet containing 200 mg, and 0,25 mg/l for one tablet containing 50 mg.
Biological availability of the dosage forms intended for intake makes about 25-35% and is characterized by considerable individual variability. Sulpiridum has linear kinetics after reception of doses in the range from 50 to 300 mg.
Sulpiridum quickly diffuses in body tissue: the seeming Vss — 0,94 l/kg. Linkng with proteins of plasma — about 40%. Gets into erythrocytes by means of passive diffusion, its concentration in plasma and erythrocytes are commensurable. Concentration of Sulpiridum in cerebrospinal fluid low also makes, on average, about 13% (4–29%) of serumal concentration. Quickly gets into a liver and kidneys, more slowly — into brain tissues (the main amount of drug collects in a hypophysis). Concentration of Sulpiridum in TsNS makes 2–5% of concentration in plasma. Gets through a placental barrier. Insignificant quantities of Sulpiridum appear in breast milk.
Sulpiridum in a human body only in small degree is exposed to metabolism and is removed by kidneys practically in not changed look by glomerular filtering (92%), and the rest eliminirutsya with excrement. Plasmatic T1/2 makes 7 h. With breast milk 0,1% of a daily dose are allocated. The general plasma clearance of Sulpiridum reaches 90–126 ml/min., at the same time the renal clearance reaches several smaller sizes, than the general plasma clearance.

Indications to use:

As monotherapy or in combination with other psychotropic drugs:
- acute and chronic schizophrenia;
- acute delirious states;
- depressions of various etiology;
- neurosises and concern at adult patients at inefficiency of usual methods of treatment (only for tablets of 50 mg);
- heavy behavior disorders (agitation, mutilation, a stereotypy) at children are aged more senior than 6 years, especially in combination with autism syndromes (only for tablets of 50 mg).

Route of administration and doses:

Inside, 1–3 times a day, washing down with a small amount of liquid, irrespective of meal. It is not recommended to accept drug in the second half of day (after 16 h) in connection with increase in level of activity.
The therapy purpose — to reach minimum effective dose.

Tablets of 200 mg
Acute and chronic schizophrenia, acute delirious psychosis, depression: the daily dose makes from 200 mg to 1000 mg, divided into several receptions.

Tablets of 50 mg
Neurosises and concern at adult patients: the daily dose makes from 50 to 150 mg during 4 weeks as much as possible.
Heavy behavior disorders at children are more senior than 6 years: the daily dose makes from 5 to 10 mg/kg of body weight.
Doses for elderly people: the initial dose has to make 1/4–1/2 doses for adults.

Features of use:

Use during pregnancy
Experiments on animals did not reveal teratogenic action. At a small number of the women accepting low doses of Sulpiridum (about 200 mg/days) during pregnancy, the teratogenic effect was absent. Concerning use of higher doses of Sulpiridum data are absent. There are no antipsychotic drugs which are also given about potential action accepted during pregnancy on development of a brain of a fruit. Therefore, as a precautionary measure it is preferable not to apply Sulpiridum during pregnancy.

However in case of use of this drug during pregnancy it is recommended to limit a dose and duration of a course of treatment as far as possible. At newborns whose mothers it is long received treatment by high doses of neuroleptics, the gastrointestinal symptoms (abdominal distention, etc.) connected with m-holinoblokiruyushchim effect of some drugs, especially in a combination with protivoparkinsonichesky means and also an extrapyramidal syndrome were seldom observed.
At long treatment of mother or use of high doses, and also in case of purpose of drug shortly before childbirth, control of activity of a nervous system both mother, and newborn is reasonable.
Drug gets into breast milk therefore it is necessary to stop administration of drug during breastfeeding.

Malignant antipsychotic syndrome: at development of a hyperthermia of the obscure etiology Sulpiridum should be cancelled since it can be one of signs of the malignant antipsychotic syndrome described at use of neuroleptics (pallor of integuments, a hyperthermia, vegetative dysfunction, consciousness disturbance, muscle tension).
Symptoms of vegetative dysfunction, such, as: the strengthened sweating and labile ABP can precede approach of a hyperthermia, and, therefore, represent the precursory guarding symptoms. Though such action of neuroleptics can have an idiosyncratic origin, apparently, some risk factors can contribute to it, for example, dehydration or organic injury of a brain.

Increase in an interval of QT: Sulpiridum extends QT interval depending on a dose. This action which, as we know, strengthens risk of development of such serious ventricular arrhythmia as "torsade des pointes" is more expressed in the presence of bradycardia, a hypopotassemia either the inborn, or acquired extended QT interval (a combination with the drug causing lengthening of an interval of QT). If the clinical situation allows, it is recommended to be convinced before purpose of drug of lack of factors which can promote development of this kind of arrhythmia:
- bradycardia with heart rate less than 55 уд. / mines;
- hypopotassemia;
- inborn lengthening of an interval of QT;
- simultaneous treatment by the drug capable to cause the expressed bradycardia (less than 55 уд. / mines), a hypopotassemia, delay of endocardiac conductivity or lengthening of an interval of QT.

Except for cases of urgent intervention, patients who need treatment by neuroleptics are recommended to carry out an ECG in the course of assessment of the status. Except exceptional cases, this drug should not be used at patients with Parkinson's disease.

At patients with disturbances of renal function it is necessary to use the reduced doses of Sulpiridum and to strengthen control; at severe forms of a renal failure carrying out the alternating courses of treatment is recommended.

Control at treatment by Sulpiridum has to be strengthened:
- at patients with epilepsy since the convulsive threshold can be lowered;
- at treatment of the elderly patients showing бóльшую sensitivity to postural hypotension, sedation and extrapyramidal effects.

During treatment by drug Prosulpin is forbidden control of vehicles and work with the mechanisms requiring special attention and also alcohol intake or use of the HP containing alcohol.

Side effects:

From TsNS: sedation, drowsiness, dizziness, a tremor, early dyskinesia (a spastic wryneck, okulogirny crises, a lockjaw) passing at purpose of the central m-holinoblokatorov; seldom — an extrapyramidal syndrome and the disturbances connected with it: the akineziya which sometimes is combined with a muscle hyper tone and which is partially eliminated at purpose of the central m-holinoblokatorov a hyperkinesia hyper tone, motive excitement, an akathisia.
Cases of the late dyskinesia which is characterized by the involuntary rhythmic movements, generally language and/or the person at long courses of treatment that can be observed during courses of treatment by all neuroleptics are noted: use of protivoparkinsonichesky drugs is inefficient or can cause deterioration in symptoms.
At development of a hyperthermia drug should be cancelled since fervescence can indicate development of a malignant antipsychotic syndrome.
From endocrine system: development of a reversible giperprolaktinemiya most of which frequent manifestations are the galactorrhoea, an amenorrhea, a dysmenorrhea is possible; more rare — impotence and frigidity.
During treatment the increased perspiration, increase in body weight can be noted by Sulpiridum.
From the alimentary system: increase in activity of enzymes of a liver.
From CCC: tachycardia, increase or decrease in the ABP is possible; development of orthostatic hypotension, lengthening of an interval of QT is in rare instances possible; very exceptional cases of development of a syndrome of "torsade des pointes".
From circulatory and lymphatic systems: hemolitic anemia, aplastic anemia, leukocytosis, Werlhof's disease, granulocytosis.
Allergic reactions: skin rash is possible.

Interaction with other medicines:

Contraindicated combinations
Agonists of dopamine receptors (амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол), except patients with Parkinson's disease
Between agonists of dopamine receptors and neuroleptics there is a mutual antagonism. At the extrapyramidal syndrome induced by neuroleptics do not apply agonists of dopamine receptors; in such cases use anticholinergics.

Suljtoprid
The risk of ventricular arrhythmias, in particular, of ciliary arrhythmias increases.

Not recommended combinations
The drugs capable to cause ventricular arrhythmias like "torsade des pointes": antiarrhytmic means of Ia of a class (quinidine, hydroquinidine, Disopyramidum) and the III class (Amiodaronum, соталол, дофетилид, ибутилид), some neuroleptics (thioridazine, Chlorpromazinum, levomepromazinum, трифлуоперазин, циамемазин, амисульприд, тиаприд, a haloperidol, Droperidolum, Pimozidum) and other drugs, such as bepridit, цизаприд, difemanit, in/in erythromycin, мизоластин, in/in Vincaminum, etc.

Alcohol
Alcohol strengthens sedative action of neuroleptics. Disturbance of attention creates danger to control of vehicles and works with the mechanisms requiring special attention. It is necessary to avoid consumption of alcoholic beverages and use of the medicines containing alcohol.

Levodopa
Mutual antagonism between a levodopa and neuroleptics. Patients with Parkinson's disease need to appoint a minimal effective dose of both drugs.
Agonists of dopamine receptors (амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол) at patients with Parkinson's disease
Between agonists of dopamine receptors and neuroleptics there is a mutual antagonism. The above-stated drugs can cause or strengthen psychoses. If treatment by Parkinson's sick with a disease neuroleptic and receiving the antagonist of dopamine receptors is necessary, the dose of the last should be lowered gradually to cancellation (sharp cancellation of agonists of dopamine receptors can lead to development of a malignant antipsychotic syndrome).

Galofantrin, pentamidine, спарфлоксацин, moxifloxacin
The risk of ventricular arrhythmias, in particular, of "torsade des pointes" amplifies. At an opportunity it is necessary to cancel the antimicrobic drug causing ventricular arrhythmia. If the combination cannot be avoided, previously it is necessary to check an interval of QT and to provide control of an ECG.

The combinations demanding care
The drugs causing bradycardia (BKK with bradikardichesky action: diltiazem, verapamil, beta adrenoblockers, clonidine, гуанфацин, cardiac glycosides; cholinesterase inhibitors: donepezil, ривастигмин, такрин, ambenoniya chloride, Galantaminum, pyridostigmine bromide, Neomycinum methyl sulfate
The risk of ventricular arrhythmias, in particular, of "torsade des pointes" amplifies. It is recommended to carry out clinical and cardiographic control.

The drugs reducing potassium concentration in blood (kaliyvyvodyashchy diuretics, purgatives of the stimulating character, Amphotericinum In (in/in), GKS, тетракозактид
The risk of ventricular arrhythmias, in particular, of "torsade des pointes" amplifies. Before purpose of drug it is necessary to eliminate a hypopotassemia, to establish clinical and cardiographic control, and also control of concentration of electrolytes.

Combinations which should be taken into account
Anti-hypertensive drugs
Strengthening of hypotensive action and increase in a possibility of postural hypotension (additive action).

Other means, the oppressing TsNS: morphine derivatives (narcotic analgetics, antibechics and replacement therapy), barbiturates, benzodiazepines and other anxiolytics, hypnotic drugs, sedatives, antidepressants, sedative blockers of H1 - histamine receptors, antihypertensives of the central action, Baclofenum, a thalidomide
Oppression of TsNS. Disturbance of attention creates danger to control of vehicles and works with the mechanisms requiring special attention.

Sukralfat, the antiacid means containing Mg2 + and/or A13+ reduce bioavailability of dosage forms for intake by 20–40%. It is necessary to appoint Sulpiridum for 2 h before their reception.

Contraindications:

- hypersensitivity to Sulpiridum or other component of drug;
- prolaktinzavisimy tumors (for example prolaktinoma of a hypophysis and breast cancer);
- giperprolaktinemiya;
- acute alcoholic poisoning, hypnagogues, narcotic analgetics;
- affective frustration, agressive behavior, maniacal psychosis;
- pheochromocytoma;
- breastfeeding period;
- children's age up to 18 years (for tablets of 200 mg);
- children's age up to 6 years (for tablets of 50 mg);

in a combination with:
- sultopridy;
- antagonists of dopamine receptors: амантадин, Apomorphinum, Bromocriptinum, каберголин, энтакапон, лизурид, перголид, piribedit, прамипексол, хинаголид, ропинирол (see the section "Interaction").

With care
Purpose of Sulpiridum is not recommended to pregnant women, except for cases when the doctor, having estimated a ratio of advantage and risk for the pregnant woman and a fruit, makes the decision that use of drug is necessary.
Purpose of Sulpiridum in a combination with the alcohol, a levodopa, drugs capable to cause ventricular arrhythmias like "torsade des pointes" is not recommended: antiarrhytmic means of Ia of a class (quinidine, hydroquinidine, Disopyramidum) and III class (Amiodaronum, соталол, дофетилид, ибутилид); some neuroleptics (thioridazine, Chlorpromazinum, levomepromazinum, трифлуоперазин, циамемазин, амисульприд, тиаприд, Pimozidum, haloperidol, Droperidolum); other drugs, such as bepridit, цизаприд, difemanit, in/in erythromycin, мизоластин, in/in Vincaminum, галофантрин, pentamidine, спарфлоксацин, moxifloxacin, etc.

Due to the existence in composition of drug of lactose, Sulpiridum is contraindicated at inborn deficit of lactase, a lactose intolerance, glyukozo-galaktozny malabsorption.

It is necessary to observe precautionary measures at purpose of Sulpiridum to patients with a renal and/or liver failure, the malignant antipsychotic syndrome (MAS) in the anamnesis, epilepsy or convulsive attacks in the anamnesis, a serious illness of heart, arterial hypertension, Parkinson's syndrome/disease, at a dysmenorrhea, at advanced age.

Overdose:

Symptoms. Experiment on overdose of Sulpiridum is limited. Specific symptoms are absent, can be observed: dyskinesia with a spastic wryneck, a protrusion of language and a lockjaw, an illegibility of visual perception, increase in the ABP, sedation, nausea, extrapyramidal symptoms, dryness in a mouth, vomiting, the increased sweating and a gynecomastia, development of ZNS is possible. Some patients have parkinsonism.

Treatment. Sulpiridum is partially removed at a hemodialysis. Due to the lack of a specific antidote it is necessary to apply a symptomatic and maintenance therapy at careful control of respiratory function and constant control of cordial activity (risk of lengthening of an interval of QT) which has to continue to an absolute recovery of the patient; holinoblokator of the central action are appointed at development of the expressed extrapyramidal syndrome.

Storage conditions:

List B.: In the dry, protected from light place, at a temperature of 15-25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 200 mg; blister 10, pack cardboard 3.

Tablets of 50 mg; blister 10, pack cardboard 3.