Solian, tablets 200 mg 30 pcs

Solian is an antipsychotic (neuroleptic)

Pharmacodynamics

. Amisulpride binds selectively, with high affinity, to D2/D3 subtypes of dopaminergic receptors, whereas it has no affinity for D1 D4 and D5 subtypes.

In contrast to classical and atypical neuroleptics, amisulpride has no affinity for serotonin receptors, histamine H1, alpha-adrenergic and cholinergic receptors. In addition, amisulpride does not bind to sigma receptors. When used in high doses, it blocks postsynaptic D2 receptors located in limbic structures, unlike similar receptors in the striatum. It does not cause catalepsy and does not lead to development of hypersensitivity of D2-dopamine receptors after repeated treatment.

In low doses, it predominantly blocks presynaptic D2/D3 receptors, causing the release of dopamine responsible for its disinhibitory effects. This atypical pharmacological profile may explain the antipsychotic effects of amisulpride at high doses resulting from blockade of postsynaptic dopamine receptors and its effectiveness against negative symptoms at low doses resulting from blockade of presynaptic dopamine receptors.
In addition, amisulpride is less likely to cause extrapyramidal side effects, which may be due to its predominant limbic activity.

In schizophrenic patients with acute seizures, Solian acts both on secondary negative symptoms and on affective symptoms such as depressed mood and retardation.

Pharmacokinetics

Amisulpride has two absorption peaks: one is reached rapidly, one hour after administration of the dose, and the second between 3 and 4 hours after administration. Plasma concentrations are 39 ± 3 and 54 ± 4 ng/mL, respectively, after administration of 50 mg.
The volume of distribution is 5.8 l/kg. Since the binding to plasma proteins is low (16%), interaction with other drugs is unlikely.

The absolute bioavailability is 48%. Amisulpride is poorly metabolized: (about 4%, two inactive metabolites have been identified. There is no cumulation of amisulpride and its pharmacokinetics remains unchanged after repeated doses.
The half-life (T1/2) of amisulpride is approximately 12 hours after an oral dose.
Amisulpride is excreted unchanged in the urine. Renal clearance is approximately 20 l/hour or 330 ml/min.
Carbohydrate-rich foods (containing 68% liquid) significantly decrease the AUC (area under the concentration/time curve), time to reach maximum concentration and maximum concentration of amisulpride itself, but no changes in pharmacokinetics were noted after eating fatty foods. However, the significance of these observations in routine clinical practice is unknown.

Hepatic impairment. Due to the fact that the drug is poorly metabolized, there is no need to reduce the dose for patients with hepatic impairment.

Hepatic impairment. The T1/2 in patients with renal impairment is not altered, but systemic clearance is reduced by a factor of 2.5 to 3. The AUC of amisulpride is doubled in mild renal insufficiency and almost tenfold in moderate insufficiency (see section Dosage and administration). Practical experience is limited, however, and there are no results for doses greater than 50 mg.

Amisulpride is poorly tolerated by dialysis.

Limited pharmacokinetic data for elderly (older than 65 years) patients indicate that Cmax, T1/2, and AUC are 10-30% higher after a single oral administration of 50 mg than in younger individuals. There are no data on the pharmacokinetics of the drug during long-term treatment.

Indications

Treatment of acute and chronic schizophrenia accompanied by markedly productive (e.g.: delusions, hallucinations, thought disorders) and/or negative (e.g.: affective flatness, lack of emotionality and withdrawal from communication) disorders, including patients with predominantly negative symptomatology.

Active ingredient

Composition

1 tablet contains

the active substance: amisulpride – 200 mg; excipients: sodium carboxymethyl starch (sodium amylopectin glycolate) (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.

How to take, the dosage

In acute psychotic episodes, oral administration in a dose of 400 to 800 mg per day is recommended. In individual cases the daily dose may be increased up to 1200 mg per day.

The doses should be increased taking into account individual tolerance.

The safety of doses greater than 1200 mg daily has not been adequately investigated, so they should not be used.

For patients with mixed negative and productive symptoms, doses should be adjusted to provide optimal control of productive symptoms.

The maintenance treatment should be set individually at the minimum effective dose level.

In patients with predominantly negative symptoms, oral doses of 50 to 300 mg per day are recommended. Dose selection should be individualized.

In doses greater than 400 mg per day, Amisulpride should be administered in 2 doses.

In elderly patients: Amisulpride should be prescribed with special caution because of the possible development of arterial hypotension or excessive sedation.

Renal failure: Excretion of amisulpride is through the kidneys. In renal failure, the dose for patients with a creatinine clearance (CRCL) of 30-60 ml/min should be reduced by half and to 1/3 for patients with a CRCL of 10 to 30 ml/min.

Interaction

Contraindicated combinations

Not recommended combinations
Amisulpride increases the CNS depressant effect of alcohol.

Combinations requiring special caution
Drugs that increase the risk of pirouette-type ventricular arrhythmias:
Drugs that cause bradycardia, such as beta-adrenoblockers, calcium channel blockers that cause bradycardia, (diltiazem and verapamil), clonidine, guanfacine; foxglove drugs.
Drugs that may cause hypokalemia: potassium-releasing diuretics, laxatives, amphotericin B, glucocorticoids, tetracosactides (hypokalemia should be corrected).
Neuroleptics such as pimozide, haloperidol; antidepressants such as imipramine; lithium.

Combinations to consider
Combination with drugs that depress CNS function, including narcotic analgesics, antipsychotics (neuroleptics), antihistamines with sedative effects, barbiturates, benzodiazepines and other anxiolytics, pronounced enhancement of depressant effects. With antihypertensive drugs – increased antihypertensive effect.

Special Instructions

A controlled double-blind study comparing amisulpride and haloperidol in patients with acute schizophrenia (191 patients) reported a significantly greater reduction in secondary negative symptoms with amisulpride. According to clinical studies, there was a significantly lower incidence of extrapyramidal symptoms with amisulpride than with haloperidol.

As with other neuroleptics, malignant neuroleptic syndrome, characterized by hyperthermia, muscle rigidity, autonomic disorders, elevated creatine phosphokinase levels may develop with amisulpride (especially high doses). If hyperthermia develops, especially with high-dose neuroleptics, all antipsychotic medications, including amisulpride, should be discontinued.

A caution should be exercised when prescribing antidopaminergic agents, and amisulpride in particular, for Parkinson’s disease, because its prescription may worsen the course of this disease. Amisulpride should only be used in patients with Parkinson’s disease if it cannot be avoided. If amisulpride treatment is needed in a patient with Parkinson’s disease who is receiving dopaminergic agonists, the dopaminergic agonists should be withdrawn gradually (by gradually reducing the dose until completely withdrawn), as abrupt withdrawal may lead to the development of a malignant neuroleptic syndrome.

Anticholinergic antiparkinsonian medications (not dopaminergic agonists) should be used to correct extrapyramidal symptoms that developed with amisulpride treatment.

Because amisulpride causes a dose-dependent prolongation of the QT interval, its administration increases the risk of paroxysmal tachycardia, including potentially life-threatening polymorphic ventricular tachycardia of the pirouette type (torsade de pointes). Therefore, if the patient’s condition allows, before prescribing amisulpride, it is recommended to take an ECG and examine the electrolyte composition of the blood, identify and, if possible, correct factors that may contribute to dangerous rhythm disturbances (bradycardia less than 55 beats per minute, hypokalemia less than 55 beats per minute, hypothyroidism less than 55 beats per minute)./(bradycardia less than 55 bpm, hypokalemia, hypomagnesemia, congenital or acquired prolonged QT, concomitant use of drugs that can cause significant bradycardia (less than 55 bpm), hypokalemia, delayed intracardiac conduction, prolonged QT interval) (see “Interactions”).

At the time of treatment with amisulpride, alcohol and alcohol-containing drugs should not be taken.

Because of the drug’s ability to lower the seizure threshold, patients with epilepsy who take amisulpride should be closely monitored clinically and, if possible, by EEG.

Some atypical neuroleptics, including amisulpride, may cause elevated blood glucose concentrations. In patients with diabetes mellitus and patients with risk factors for diabetes mellitus, blood glucose concentrations should be monitored regularly when amisulpride is prescribed.

In elderly patients, amisulpride, like other neuroleptics, should be used with extreme caution because of the possible risk of arterial hypotension or excessive sedation.

In randomized clinical trials conducted in a group of elderly patients with dementia treated with certain atypical antipsychotics, a three-fold increase in the risk of cerebrovascular events (acute cerebrovascular events) was observed compared to placebo. The mechanism of this increased risk is unknown. An increase in such risk cannot be excluded with other antipsychotic drugs or in 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, an increased risk of death has been observed with antipsychotic treatment. An analysis of 17 placebo-controlled trials (mean duration greater than 10 weeks) showed that most patients treated with atypical antipsychotics had a 1.6-1.7-fold greater risk of death than patients treated with placebo. Although the causes of death in clinical trials with atypical antipsychotics varied, most causes of death were either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies have confirmed that, like treatment with atypical antipsychotics, treatment with conventional antipsychotics can also increase mortality. The extent to which the increase in mortality may be due to the antipsychotic medication, rather than to some patient characteristics, is unclear.

There have been cases of venous thromboembolism, sometimes fatal, with the use of antipsychotic drugs. Therefore, amisulpride should be used with caution in patients with risk factors for thromboembolism (see side effects).

The excretion of amisulpride is by the kidneys. If renal function is impaired, the dose of the drug should be reduced (see “Dosage and administration”).

Impact on the ability to drive or operate vehicles or other machinery. Patients, especially those who drive vehicles or operate machinery, should be advised of the possibility of drowsiness and decreased psychomotor reactions while taking amisulpride, especially at the beginning of treatment, as this may be dangerous when driving or operating machinery.

Contraindications

With caution – pregnancy, epilepsy, parkinsonism, old age, renal failure.

Side effects

Adverse reactions (HP) are presented according to the following frequency gradations: Very common (≥10%); common ( ≥1%, < 10%); infrequent (≥0.1%,< 1%); rare (≥0.01%, < 0.1%); very rare, including individual reports (< 0.01%) ; frequency unknown (the incidence of HP cannot be determined from available data).

Blood and lymphatic system disorders

Infrequent: leukopenia, neutropenia (see section “Special indications”).

Rarely: agranulocytosis (see section “Special Precautions”).

Immune system disorders

Infrequent: allergic reactions.

Endocrine system disorders

Often: amisulpride causes an increase in plasma concentrations of prolactin, reversible after discontinuation of the drug. This may lead to galactorrhea, amenorrhea, gynecomastia, breast pain, and erectile dysfunction.

Rarely: a benign tumor of the pituitary gland, such as prolactinoma.

Metabolic and nutritional disorders

Often: weight gain.

Infrequent: hyperglycemia (see sections “Caution” and “Special indications”), hypertriglyceridemia, hypercholesterolemia.

Rarely: hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

Mental disorders

Often: insomnia, anxiety, agitation, impaired orgasm (orgasmic dysfunction).

Infrequent: confusion.

Nervous system disorders

Very common: extrapyramidal symptoms (tremor, rigidity, hypokinesia, hypersalivation, akathisia, dyskinesia). These symptoms are usually moderate when taken at optimal doses and partially reversible when anticholinergic antiparkinsonian drugs are added without discontinuing amisulpride treatment. The incidence of extrapyramidal symptoms is dose dependent. Therefore, the incidence of extrapyramidal symptoms is very low in patients with predominantly negative symptoms taking amisulpride at a dose of 50-300 mg daily.

The incidence of extrapyramidal symptoms was significantly lower with amisulpride than with haloperidol, according to clinical studies.

Often: acute dystonia (spastic torticollis, oculogyric crisis, trismus) reversible with addition of anticholinergic antiparkinsonian drugs without stopping amisulpride treatment ; somnolence.

Infrequent: tardive dyskinesia characterized by rhythmic, involuntary movements mainly of the tongue and/or facial muscles, and occurring usually after long-term administration of the drug (anticholinergic antiparkinsonian drugs are ineffective in these cases or may exacerbate the symptoms); seizures.

Rarely: malignant neuroleptic syndrome, which is a potentially fatal complication (see section “Special Precautions”).

Prevalence unknown: restless legs syndrome with or without akathisia.

Visual disturbances

Often: blurred vision.

Heart disorders

Infrequent: bradycardia.

Rarely: prolongation of QT interval; ventricular rhythm disturbances such as pirouette-type polymorphic ventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrest and sudden death (see “Special Instructions”).

Vascular disorders

Often: decreased blood pressure.

Infrequent: increase in blood pressure.

Rarely: venous thromboembolic complications, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section “Special Precautions”).

Respiratory, chest and mediastinal disorders

Infrequent: nasal congestion; aspiration pneumonia (mainly when combined with other antipsychotics and CNS depressants).

Gastrointestinal disorders

Often: constipation, nausea, vomiting, dry mouth.

Liver and biliary tract disorders

Infrequent: hepatocellular lesions.

Skin and subcutaneous tissue disorders

Rarely: angioedema, urticaria.

Prevalence unknown: photosensitization.

Musculoskeletal and connective tissue disorders

Infrequent: osteopenia, osteoporosis.

Renal and urinary tract disorders

Infrequent: urinary retention.

Injuries, complications and complications of manipulation

Frequency unknown: falls (sometimes leading to fractures) as a consequence of the development of adverse reactions associated with possible balance disorders.

Pregnancy, postpartum and perinatal conditions

Prevalence unknown: “withdrawal” syndrome in newborns (see

Pregnancy and Breastfeeding Use

Pregnancy and Breastfeeding Use

Pregnancy and Breastfeeding.)

Laboratory disorders

Infrequent: increased activity of “liver” enzymes in blood, mainly transaminases.

Overdose

Symptoms: Experience with amisulpride overdose is very limited. Significant increases in the known pharmacological effects of the drug have been reported, namely drowsiness, sedation, coma, arterial hypotension and extrapyramidal symptoms.

Please be aware that overdose phenomena may occur if additional doses of the drug are taken by mistake or if other drugs are taken at the same time.

Treatment: There is no specific antidote for amisulpride.

In case of overdose, basic vital body functions should be monitored and maintained until the patient is completely out of overdose. In overdose, ECG monitoring is mandatory because there is a risk of prolongation of the QT interval and development of life-threatening rhythm disturbances (see side effects).

In case of severe extrapyramidal symptoms, anticholinergic agents should be used.

Because excretion of amisulpride by hemodialysis is negligible, hemodialysis is not appropriate for its excretion in overdose.

Pregnancy use

The safety of amisulpride administration during pregnancy has not been established.

Hence, use of the drug in pregnancy is not recommended unless the expected benefit to the mother justifies the potential risk to the fetus.

While there have been no reports of adverse events in neonates, amisulpride when used late in pregnancy and in high doses can theoretically cause adverse events in neonates (atropine-like effects: tachycardia, hyperreflexia, bloating, delayed meconium discharge; extrapyramidal symptoms: hypertonicity, tremor; sedation) and therefore they may need appropriate monitoring.

It is not known whether amisulpride is able to penetrate into breast milk, so breastfeeding is contraindicated during its administration.