Solian - instructions for use, dose, side effects, contraindications

Active substanceAmisulprideAmisulpride

Similar drugsTo uncover

Limipranil

pills inwards

AKTAVIS GROUP, AO Iceland

Limipranil

pills inwards

AKTAVIS GROUP, AO Iceland

Solian®

solution inwards

Sanofi-Aventis France France

Solian®

pills inwards

Sanofi-Aventis France France

Dosage form: & nbsppills

Composition:

Tablets 100 mg

In 1 tablet contains the active substance: amisulpride - 100 mg;

auxiliary substances: sodium carboxymethyl starch (sodium amylopectin glycolate) (type A) 24 mg, lactose monohydrate 69.6 mg, microcrystalline cellulose 36 mg, hypromellose 6.8 mg, magnesium stearate 3.6 mg.

Tablets 200 mg

In 1 tablet contains the active substance: amisulpride - 200 mg;

auxiliary substances: carboxymethyl starch sodium (sodium amylopectin glycolate) (type A) 48 mg, lactose monohydrate 139.2 mg, cellulose microcrystalline 72 mg, hypromellose 13.6 mg, magnesium stearate 7.2 mg.

Description:

Tablets 100 mg: round flat tablets white or almost white with a dividing risk on one side and engraving "AMI 100 "- on the other.

Tablets 200 mg: round flat tablets of white or almost white color with a dividing risk on one side and engraving " AMI 200 "on the other.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic).

ATX: & nbsp

N.05.A.L.05 Amisulpride

Pharmacodynamics:

Amisulpride is an antipsychotic drug from the group of substituted benzamides.

The pharmacodynamic profile of amisulpride is due to selective and preferential affinity for the subtypes D2 and D3 of the dopamine receptors of the limbic system. Amisulpride has no affinity for serotonin and other neuroreceptors, such as histamine, cholinergic and adrenergic receptors.

In animal studies, it has been shown that when used in high doses amisulpride to a greater degree blocks dopaminergic neurons of the mesolimbic system than analogous neurons in the striatum system. This specific affinity explains, apparently, the predominance of antipsychotic effects of amisulpride over its extrapyramidal effects.

When used in low doses amisulpride predominantly blocks presynaptic D2 and D3 dopamine receptors, which can explain its positive effect on negative symptoms.

Pharmacokinetics:

Amisulpride has two absorption peaks: one is achieved quickly, after an hour, and the second - between 3 and 4 hours after taking the drug.After taking the drug at a dose of 50 mg, the maximum concentrations in the plasma (C_max) corresponding to these peaks are 39 ± 3 ng / ml and 54 ± 4 ng / ml.

The volume of distribution is 5.8 l / kg. Due to the low binding to plasma proteins (16%), no interaction of amisulpride with other drugs is expected at the level of binding to the protein. Absolute bioavailability is 48%.

Amisulpride is slightly metabolized in the liver (about 4%), two inactive metabolites are identified. At the course of reception of cumulation of amisulpride does not occur, and its pharmacokinetics does not change. When administered orally, the half-life (T1 / 2) of amisulpride is approximately 12 hours.

Amisulpride is excreted unchanged in urine.

Kidney clearance is approximately 330 ml / min.

A carbohydrate-rich diet significantly reduces the area under the concentration / time curve (AUC), the time to reach the maximum concentration (T_max) and C_m_ax amisulpride, while the fat-rich diet does not cause changes in the above pharmacokinetic parameters. However, the importance of these observations in everyday clinical practice is unknown.

Renal insufficiency

T 1/2 in patients with renal insufficiency does not change, but the systemic clearance decreases with a coefficient of 2.5 to 3. AUC amisulpride in mild renal insufficiency is doubled, and in renal insufficiency of moderate severity - almost tenfold (see "Method of administration and dose"). Experience with the drug in renal failure is limited, and there is no data on the use of amisulpride in a dose exceeding 50 mg.

Amisulpride is practically not excreted by hemodialysis.

Liver failure

Due to amisulpride is slightly metabolized in the liver, liver failure is not expected to accumulate the drug, and its dosage is not required.

Elderly patients

When comparing the pharmacokinetic parameters of patients older than 65 years with those in younger patients, it was found that after single ingestion of amisulpride in a dose of 50 mg, the value of Cmah, T1 / 2 and AUC higher by 10-30%. Data on the pharmacokinetics in elderly patients with the course of amisulpride are absent.

Indications:

Treatment of acute and chronic schizophrenia with productive symptoms (delirium, hallucinations, thinking disorders) and / or negative symptoms (flattening affect, loss of emotional and social ties), including patients with predominance negative symptoms.

Contraindications:

- Hypersensitivity to amisulpride or other components of the drug.

- Concomitant prolactin-dependent tumors, for example, pituitary prolactinoma and breast cancer.

- Pheochromocytoma (diagnosed or suspected).

- Children and adolescents under 18 years of age (lack of clinical experience).

- The period of breastfeeding.

- Severe renal failure with creatinine clearance less than 10 ml / min (lack of clinical experience).

- Concomitant therapy with dopamine receptor agonists (cabergoline, quinagolide) when they are used not for the treatment of Parkinson's disease (see section "Interaction with other drugs").

- Concomitant therapy with levodopa, amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, pyribedil, pramipexole, ropinirole, selegiline (see.section "Interaction with other drugs").

- Concomitant therapy with drugs that can prolong the QT interval and cause the development of rhythm disturbances, including a potentially life-threatening ventricular torsade des pointes (see "Interactions with Other Drugs"):

antiarrhythmic drugs IA class (quinidine, disopyramide) and III class (amiodarone, sotalol, dofetilide, ibutilide);

other medicines (beprideal, cisapride, methadone, sultopride, thioridazine, diphenylmethyl methyl sulfate, administered intravenously erythromycin, administered intravenously spiramycin, misolastine administered intravenously wincamine, halofantrine, lumefantrine, sparfloxacin, moxifloxacin, pentamidine, citalopram, escitalopram).

- Congenital galactosemia, glucose malabsorption syndrome or galactose, or lactase deficiency.

Carefully:

- In patients with predisposing factors of severe ventricular arrhythmias, including potentially life-threatening ventricular torsade des pointes (torsade des pointes) (amisulpride is able to dose-dependently extend the QT interval and increase the risk of developing severe ventricular arrhythmias,including ventricular pirouette (torsade des pointes)) (see the sections "Side effect", "Interaction with other drugs"):

- in patients with congenital prolonged QT interval;

- in patients with acquired QT interval prolongation (when combined with drugs increasing the duration of the QTc interval, except as indicated in the "Contraindications" section) (see section "Interaction with other drugs");

- in patients with bradycardia less than 55 beats per minute;

- in patients with electrolyte disorders, including hypokalemia;

- in patients receiving concomitant therapy with drugs that can cause hypokalemia, a pronounced bradycardia of less than 55 beats per minute, slow intracardiac conduction.

- In patients with renal insufficiency, since there is a risk of cumulation of the drug, the experience of its use in renal failure is limited (see sections "Pharmacokinetics", "Dosage and administration", "Special instructions").

- In elderly patients, as they have an increased predisposition to lowering blood pressure and developing excessive sedation.

- In elderly patients with dementia (see section "Special instructions").

- In patients with risk factors for stroke (see section "Special instructions").

- In patients with epilepsy, since amisulpride can reduce the threshold of convulsive readiness.

- In patients with risk factors for venous thromboembolic complications (see "Side effects", "Special instructions").

- In patients with Parkinson's disease, since amisulpride, like other dopamine receptor blockers, can enhance the manifestations of Parkinson's disease (see section "Special instructions").

- In patients with diabetes mellitus and patients with risk factors for diabetes mellitus (since some atypical antipsychotics, including amisulpride, can cause an increase in the concentration of glucose in the blood).

Pregnancy and lactation:

Pregnancy

Safety of reception of amisulpride during pregnancy is not established. Therefore, the use of the drug in pregnancy is not recommended, except when the expected benefit for the mother justifies the potential risk to the fetus. Women of reproductive age should take contraceptive when taking amisulpride. Newborns,which have been exposed during the third trimester of pregnancy to the intrauterine effects of antipsychotics, including Solian®, have the risk of developing unwanted reactions after birth, including extrapyramidal symptoms or withdrawal syndrome, which may vary in severity and duration (see "Side effect" ). The development of excitation, muscular hypertonia, muscle hypotension, tremor, drowsiness, respiratory distress or feeding disorders has been reported. Therefore, such newborns should be under constant medical supervision.

Breastfeeding period

It is not known whether amisulpride penetrate into breast milk, so breast-feeding during its administration is contraindicated.

Preclinical research data

In studies conducted on animals, amisulpride did not demonstrate reproductive toxicity. There was a decrease in fertility associated with the pharmacological effects of amisulpride (the effect mediated by prolactin).

Dosing and Administration:

The drug is intended for oral administration.

Usually, if the daily dose does not exceed 400 mg, it can be taken once a day. If the daily dose exceeds 400 mg, then it should be divided into two doses. With the prevalence of negative symptoms

For patients with a predominantly negative symptomatology, the use of amisulpride in a dose of 50 to 300 mg per day (average 100 mg per day) is recommended. Selection of the dose should be carried out individually.

In mixed episodes with productive and negative symptoms

For patients with mixed (negative and productive) symptoms, the dose should be selected to provide optimal control over the productive symptoms, on average they range from 400 mg to 800 mg. Supportive treatment should be set individually at the level of minimum effective doses (depending on the patient's response).

Acute psychotic episodes

Start treatment

Doses of 400 to 800 mg are used. The maximum dose should never exceed 1200 mg per day.

Supportive therapy

Subsequently, the selected dose is preserved or adjusted depending on the patient's response. In all cases, maintenance doses should be set individually at the level of minimally effective doses.

In patients with renal insufficiency

The clinical experience of the drug in patients with impaired renal function is limited. Excretion of amisulpride is carried out through the kidneys. In case of renal insufficiency, the dose for patients with creatinine clearance of 30-60 ml / min should be reduced by half, and for patients with creatinine clearance from 10 to 30 ml / min - three times. There are no data on the intake of amisulpride in a dose exceeding 50 mg. In connection with the lack of data on the use of the drug in patients with creatinine clearance less than 10 ml / min, the use of amisulpride in this group of patients is contraindicated (see the section "Contraindications").

In patients with hepatic insufficiency

Due to the fact that the drug is poorly metabolized in the liver, reducing its dose with liver failure is not required.

In elderly patients

When using the drug elderly patients should be especially careful (see section "Special instructions").

Children

The efficacy and safety of amisulpride in children and adolescents under 18 years of age have not been established. The use of amisulpride in patients younger than 18 years is contraindicated (see the section "Contraindications").There are limited data on the use of amisulpride in adolescents with schizophrenia.

Side effects:

Undesired reactions (HP) are presented in accordance with the following gradations of their frequency of development: very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%); very rarely, including individual reports (<0.01%); the frequency is unknown (according to available data, it is not possible to determine the frequency of HP development).

Below listed HP, observed in controlled clinical trials and in the post-marketing application of the drug (the incidence of HP observed in the post-marketing use of the drug is listed as "frequency unknown").

It should be noted that in some cases it is very difficult to differentiate HP from the symptoms of the underlying disease.

Disturbances from the nervous system

Often

Extrapyramidal symptoms (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia). These symptoms are usually mild when taken at optimal doses and partially reversible with the addition of anticholinergic antiparkinsonian drugs without discontinuing amisulpride treatment. The incidence of extrapyramidal symptoms depends on the dose.Therefore, in patients with predominantly negative symptoms receiving amisulpride in a dose of 50-300 mg, the incidence of extrapyramidal disorders is very low. According to clinical studies with amisulpride, there was a significantly lower incidence of extrapyramidal symptoms than with haloperidol.

Often

Acute dystonia (spasmodic torticollis, oculogic crises, trism), reversible with the addition of anticholinergic antiparkinsonian drugs without discontinuing amisulpride treatment. Daytime sleepiness.

Infrequently

Late dyskinesia characterized by rhythmic, involuntary movements predominantly of the tongue, and / or facial muscles, usually occurring after a prolonged use of the drug. Anticholinergic antiparkinsonian drugs in these cases are not effective or may enhance symptoms. Seizures convulsions.

Frequency unknown

Malignant neuroleptic syndrome, which is a potentially lethal complication (see section "Special instructions"). Disorders of the psyche.

Often

Insomnia, a sense of anxiety, agitation, a violation of orgasm (orgasmic dysfunction).

Frequency unknown

Confusion of consciousness.

Disorders from the gastrointestinal tract

Often

Constipation, nausea, vomiting, dry mouth.

Disorders from the endocrine system

Often

Amisulpride causes an increase in plasma concentrations of prolactin, reversible after drug withdrawal. This can lead to the occurrence of galactorrhea, amenorrhea, gynecomastia, pain in the breast (breast) glands and erectile dysfunction.

Disorders from the metabolism and nutrition

Often

Weight gain.

Infrequently

Hyperglycemia (see Fig. sections "Contraindications", "With caution" and "Special instructions").

Frequency unknown

Hypertriglyceridemia, hypercholesterolemia.

Disorders from the cardiovascular system

Often

Reduced blood pressure.

Infrequently

Bradycardia.

Frequency unknown

Elongation of the QT interval, ventricular rhythm disturbances, such as polymorphic ventricular tachycardia such as "pirouette" (torsade des pointes), which can transform into ventricular fibrillation and lead to heart failure and sudden death (see p.section "Special instructions"). Venous thromboembolic complications, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section "Special instructions").

Violations from laboratory indicators

Infrequently

Increased activity of "hepatic" enzymes in the blood, mainly transaminases.

Immune system disorders

Infrequently

Allergic reactions.

Frequency unknown

Angioedema, hives.

Violations of the blood and lymphatic system

Frequency unknown

Leukopenia, neutropenia, agranulocytosis (see section "Special instructions").

Pregnancy, postpartum and perinatal conditions

Frequency unknown

The syndrome of "cancellation" in newborns (see the section "Application during pregnancy and during breast-feeding").

Overdose:

Symptoms

Overdose reported a significant increase in known pharmacological effects of the drug, namely, the development of drowsiness, sedation, excessive lowering of blood pressure, extrapyramidal symptoms and coma. There were reports of fatalities in overdose, mainly when combined with other psychotropic drugs.It should be borne in mind that an overdose can be caused by the simultaneous intake of several drugs

Treatment

There is no specific antidote for amisulpride. In case of an overdose, the basic vital functions of the body should be monitored and maintained until the patient leaves the overdose state completely. In case of an overdose, ECG monitoring is mandatory, as there is a risk of prolonging the QT interval and developing life-threatening rhythm disturbances (see "Side-Effects" section). In the case of severe extrapyramidal symptoms, m-holinoblokatory central action, for example, trihexyphenidyl.

Since the excretion of amisulpride with hemodialysis is insignificant, it is not advisable to use hemodialysis to remove it in an overdose.

Interaction:

Contraindicated combinations

With drugs that can prolong the QT interval and cause paroxysmal tachycardias, including a potentially lethal polymorphic ventricular tachycardia such as pirouette (torsade des pointes):

- with antiarrhythmic drugs of IA class (quinidine, disopyramide) and III class (amiodarone, sotalol, dofetilide, ibutilide); with bepridilom, cisapride, methadone, sultoprid, thioridazine, dipemannil methyl sulphate, erythromycin (intravenously), spiramycin (intravenously), misolastine, vincamine (intravenously), halofantrine, lumefantrine, sparfloxacin, gatifloxacin, moxifloxacin, pentamidine.

- with citalopram, escitalopram.

The risk of developing paroxysmal tachycardias increases, including potentially lethal polymorphic ventricular tachycardia of the pirouette (torsade des pointes) type (see "Contraindications").

With dopamine receptor agonists (cabergoline, quinagolide) when used not for the treatment of Parkinson's disease

Mutual antagonism of the effects of dopamine receptor agonists and neuroleptics. Dopamine receptor agonists can cause or exacerbate psychotic symptoms.

With levodopa (see the section "Contraindications")

Reciprocating antagonism of the effects of levodopa and antipsychotics.

Unrecommended combinations

With drugs that increase the risk of potentially lethal polymorphic ventricular tachycardia such as "pirouette" (torsade des pointes)

With drugs that cause bradycardia (beta-adrenoblockers, verapamil, diltiazem, clonidine, guanfacine, cardiac glycosides, donepezil, rivastigmine, tacrine, ambenonium chloride, galantamine, pyridostigmine bromide, neostigmine bromide);

With drugs that cause hypokalemia (with diuretics that cause hypokalemia, laxatives that simulate intestinal peristalsis, intravenously injected amphotericin B, glucocorticosteroids, tetracosactides) - when applied it is necessary to restore potassium losses and maintain a normal level of potassium in the blood;

With some neuroleptics (haloperidol, pimozide, pipothiazine, sertindole, chlorpromazine, levomepromazine, ciamemazine, sultopride, sulpiride, tiaprid, verialapride, droperidol), imipramine antidepressants, lithium preparations, azole antifungal agents.

The risk of developing ventricular arrhythmias increases, in particular, ventricular torsade desiases (torsade des pointes).

With ethanol

Amisulpride enhances the central effects of ethanol. Ethanol increases the sedative effect of neuroleptics.

With dopamine receptor agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline) (see the sections "Contraindications" and "Special instructions") Mutual antagonism effects dopamine receptor agonists and neuroleptics.

Dopamine receptor agonists can cause or exacerbate psychotic symptoms. Amisulpride can enhance the symptoms of Parkinson's disease.

Combinations that should be taken into account

With agents that depress the central nervous system: morphine derivatives (analgesics, antitussive drugs); barbiturates; benzodiazepines; non-benzodiazepine anxiolytics, hypnotics; antidepressants with sedative effect (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); H2 histamine receptor blockers with sedative effect; antihypertensive agents of central action (clonidine); neuroleptics, baclofen; thalidomide, pisotifen.

Expressed increased oppressive effect on the central nervous system. An additional reduction in the concentration of attention, which creates a great danger for transport drivers and persons,working with mechanisms.

With antihypertensive drugs, including beta-blockers (bisoprolol, carvedilol, metoprolol)

The risk of developing arterial hypotension, in particular, orthostatic hypotension (additive effect). For beta-blockers, see the section on "Interaction with other drugs" in the section "Non-recommended combinations".

Special instructions:

A controlled double-blind study comparing amisulpride and haloperidol in patients with acute schizophrenia (191 patients) with amisulpride showed a significantly greater decrease in secondary negative symptoms. According to clinical studies with amisulpride, there was a significantly lower incidence of extrapyramidal symptoms than with haloperidol. As with the use of other neuroleptics, with the use of amisulpride (especially high doses), a malignant neuroleptic syndrome can develop, a potentially lethal complication characterized by hyperthermia, muscle rigidity, autonomic disorders, increased creatine phosphokinase concentration.With the development of hyperthermia, especially when high doses of antipsychotics are used, all antipsychotics, including amisulpride, should be canceled.

Caution should be exercised when using blockers of dopamine receptors and in particular amisulpride in Parkinson's disease, as it may worsen the course of this disease. In patients with Parkinson's disease amisulpride It should be used only if it can not be avoided. If a patient with Parkinson's dopamine receptor agonists needs treatment with amisulpride, then dopamine receptor agonists should be abolished gradually (by gradually reducing the dose until they are completely eliminated), as abrupt reversal can lead to the development of a malignant neuroleptic syndrome.

To correct the extrapyramidal symptoms that have arisen against amisulpride, m-holinoblockers of central action (and not dopamine receptor agonists) should be used. Due to amisulpride causes a dose-dependent increase in the duration of the QT interval,when taking it, the risk of developing paroxysmal tachycardias increases, including a potentially life-threatening ventricular torsade des pose (torsade des pointes). Therefore, if the patient's condition allows, before using amisulpride, it is recommended to remove the ECG and determine the concentration of electrolytes in the blood, to identify and, if possible, to correct factors that may contribute to the occurrence of these dangerous rhythm disturbances (such as bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia , congenital or acquired lengthening of QT interval, simultaneous reception of drugs capable of causing pronounced bradycardia (less than 55 beats per minute), hypokalemia, slowing of intracardiac second conductivity prolong the QT interval) (see. the section "Interaction with other drugs").

During treatment with amisulpride, you can not take ethanol and medicines containing ethanol.

Due to the ability of the drug to lower the threshold of convulsive readiness, when receiving amisulpride patients with epilepsy, they should be followed by a thorough clinical and, if possible, electroencephalographic observation.

Some atypical antipsychotics, including amisulpride, can cause an increase in the concentration of glucose in the blood. In patients with diabetes mellitus and patients with risk factors for diabetes mellitus, the concentration of glucose in the blood should be monitored regularly with amisulpride.

In elderly patients amisulpride, like other antipsychotics, should be used with extreme caution because of the possible risk of lowering blood pressure or excessive sedation.

In randomized clinical trials conducted in a group of elderly patients with dementia who received treatment with some atypical antipsychotics, there was a triple increase in the risk of developing cerebrovascular complications (acute cerebrovascular accidents), compared with placebo. The mechanism of this increase in risk is unknown. It is not possible to exclude an increase in this risk with the use of other antipsychotics or in other groups of patients. Amisulpride should be used with caution in patients with risk factors for stroke.

In elderly patients with psychoses associated with dementia, in the treatment of antipsychotic drugs, there was an increased risk of death.An analysis of 17 placebo-controlled trials (average duration of more than 10 weeks), conducted mainly in patients receiving atypical antipsychotics, showed that they had a 1.6-1.7 times greater risk of death than patients who received placebo. In a typical 10-week study, the incidence of death in patients receiving these drugs was 4.5% compared to that in the placebo group, which was 2.6%. Although the causes of death in clinical trials with atypical antipsychotics varied, most of the causes of death were cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) nature.

Observational studies have confirmed that, like treating atypical antipsychotics, treatment with conventional antipsychotics can also increase mortality. The extent to which an increase in mortality may be due to an antipsychotic drug, rather than to certain features of patients, is unclear.With a sharp discontinuation of high therapeutic doses of neuroleptics, cases of the development of the "withdrawal" syndrome were described. When amisulpride was taken, there was reported the occurrence of involuntary motor disorders, such as akathisia, a violation of muscle tone and dyskinesia. Therefore, with the abolition of amisulpride, a gradual dose reduction is recommended.

When using antipsychotic drugs, there have been cases of venous thromboembolic complications, sometimes lethal. therefore amisulpride should be used with caution in patients with risk factors for venous thromboembolic complications (see section "Side effect"). The excretion of amisulpride is carried out by the kidneys. If the renal function is impaired, the dose of the drug should decrease (see section "Method of administration and dose"). When using antipsychotic drugs, including Solian®, leukopenia, neutropenia and agranulocytosis were observed. Infectious or febrile infections can be associated with hematologic disorders (see the "Side effect" section) and require an immediate hematological examination.

Effect on the ability to drive transp. cf. and fur:

It is necessary to inform patients, especially those who are drivers of vehicles or working with mechanisms, as well as persons engaged in other potentially hazardous activities, about the possibility of their drowsiness and psychomotor reactions during the administration of amisulpride, especially at the beginning of treatment, as this may be dangerous when dealing with these activities, requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 100 mg and 200 mg.

Packaging:For 10 tablets in a blister of PVC / Aluminum foil. For 3 blisters with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

Shelf life 3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015518 / 01

Date of registration:26.12.2008

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp19.11.2014

Illustrated instructions

Instructions

Solian® (Solian®)