Solian, 400 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.

Unlike classical and atypical neuroleptics, amisulpride has no affinity for serotonin, 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 remain 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

Acute and chronic schizophrenia accompanied by pronounced productive (including delusions, hallucinations, thought disorders) and/or negative (including affective flatness, lack of emotionality and withdrawal from communication) disorders, including in patients with predominantly negative symptomatology.

Active ingredient

Composition

1 tablet contains

the active substance: amisulpride – 400 mg;

excipients: sodium carboxymethyl starch (sodium amylopectin glycolate) (type A), lactose monohydrate, microcrystalline cellulose, hypromellose, magnesium stearate.

The composition of the shell. hypromellose, microcrystalline cellulose, macrogoal stearate, titanium dioxide (E 171).

How to take, the dosage

In acute psychotic episodes, the recommended dose is 400 to 800 mg/day. In individual cases, if necessary, the dose may be increased to 1200 mg/day. Doses are increased taking into account individual tolerability of the drug. The maximum daily dose should not exceed 1200 mg.

In mixed negative and productive symptoms, doses should be tailored to provide optimal control of productive symptoms: average of 400 mg to 800 mg/day Maintenance treatment should be set individually at the minimum effective doses.

The recommended daily dose ranges from 50 to 300 mg. Dose selection should be individualized.

In elderly patients, Solian should be prescribed with extreme caution because of the possible development of arterial hypotension or excessive sedation.

In doses greater than 400 mg/day, Solian should be prescribed in 2 doses.

For ease of dosing, Solian Table.o.400 mg disp. 30 Sanofi-Aventis.

Interaction

Combinations that are contraindicated: With dopaminergic agonists (including amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, pyribedil, pramipexole, quinagolide, ropinirole, selegiline), except in patients with Parkinson’s disease. Dopaminergic agonists and neuroleptics show mutual antagonism.

In extrapyramidal syndrome caused by neuroleptics, anticholinergic drugs should be used instead of dopaminergic agonists. Concomitant use of Solian with sultopride increases the risk of ventricular arrhythmias, particularly atrial fibrillation.

Combinations not recommended: With drugs that may cause pirouette-type arrhythmias: Class Ia antiarrhythmic drugs (including quinidine, hydroquinidine, disopyramide ) and Class III drugs (including amiodarone, sotalol, dofetilide, ibutilide), some neuroleptics (including Thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, thiapride, pimozide, haloperidol, droperidol ) and other drugs (incl. Bepridil, cisapride, difemanil, IV erythromycin, misolastin, IV vincamine, halofantrine, sparfloxacin, gatifloxacin, moxifloxacin, pentamidine, IV spiramycin).

The risk of ventricular arrhythmias, particularly the development of pirouette-type arrhythmias, increases. If the combination of drugs cannot be avoided, perform QT interval control and initiate ECG monitoring before prescribing. Ethanol enhances the sedative effects of neuroleptics. Alcohol consumption and use of drugs containing alcohol should be avoided. Mutual antagonism between levodopa and neuroleptics should be considered when prescribing these drugs. In patients with Parkinson’s disease, the use of minimal effective doses of both drugs is recommended.

Combinations requiring special caution: With drugs that cause bradycardia (including Beta-adrenoblockers /except sotalol/calcium channel blockers that cause bradycardia – diltiazem and verapamil ), clonidine, guanfacine, foxglove drugs, cholinesterase inhibitors (including donepezil, rivastigmine, tacrine, ambenonium, galantamine, pyridostigmine, neostigmine).

With drugs that may cause hypokalemia (including potassium withdrawing diuretics, laxatives, IV amphotericin B, glucocorticoids, tetracosactides). With the above drug combinations, the risk of ventricular arrhythmias, especially the development of pirouette-type arrhythmias, remains.

Combinations to be taken into account: With antihypertensive agents and beta-blockers in heart failure (including bisoprolol, carvedilol, metoprolol) has a vasodilator effect, increasing the risk of orthostatic hypotension (additive effect).

With morphine derivatives (including analgesics, anti-cough drugs), barbiturates, benzodiazepines and other anxiolytics, hypnotics, sedative antidepressants (including Amitriptyline, doxepin, mianserine, mirtazapine, trimipramine ), sedative antihistamines, central antihypertensive agents, neuroleptics and other drugs (including baclofen, thalidomide, pizotifen ) lead to markedly increased CNS depression (reduced attention span and danger to drivers and machine operators).

Special Instructions

The development of malignant neuroleptic syndrome characterized by hyperthermia, muscle rigidity, peripheral nervous system dysfunction, elevated CPK levels is possible. If hyperthermia develops, especially with high-dose use, all antipsychotic drugs (including Solian) should be discontinued.

As amisulpride is excreted by the kidneys, the drug dose and therapy regimen should be adjusted if renal function is seriously impaired. There is no experience of this medicine use in patients with severe renal dysfunction (CKG less than 10 ml/min).

As the drug is poorly metabolized, no dose reduction is required in patients with impaired hepatic function.

Due to the possible lowering of the seizure threshold when using amisulpride, patients with a history of epilepsy require continuous monitoring during therapy with Solian.

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

In Parkinson’s disease, caution should be exercised when prescribing antidopaminergic drugs and amisulpride because of the possible worsening of the condition. Amisulpride should be used only if neuroleptic therapy cannot be avoided.

Amisulpride causes dose-dependent prolongation of the QT interval, thereby increasing the risk of serious ventricular arrhythmias (pirouette type). Before prescribing the drug, and, if possible, depending on the clinical condition of the patient, it is recommended to control the factors contributing to arrhythmias: bradycardia (heart rate less than 55 bpm), hypokalemia, congenital prolongation of the QT interval.

In patients who require long-term treatment with neuroleptics, an ECG should be performed during the initial status evaluation.

Due to the lactose content of the tablets, the drug is contraindicated in congenital galactosemia, glucose or galactose malabsorption syndrome or lactase deficiency.

Application in hepatic impairment: No dose reduction is required when prescribing the drug in patients with hepatic impairment.

Application in renal dysfunction: The drug is contraindicated in severe renal failure (CKR less than 10 ml/min).

Impact on ability to drive and operate machinery: Amisulpride affects reaction speed, and as a result the ability to engage in potentially dangerous activities may be impaired.

Contraindications

– Concomitant prolactin-dependent tumors (including prolactinoma of the pituitary gland, breast cancer).
– Pheochromocytoma.
– Severe renal insufficiency (CK less than 10 ml/min).
– Combined use with sultopride.
– Combined use with dopaminergic agonists (including amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, pyribedil, pramipexole, quinagolide, ropinirole, selegiline ) except in patients with Parkinson’s disease.
– Children under 14 years old.
– Lactation period (breast-feeding).
– Hypersensitivity to amisulpride and other components of the preparation.

The drug should be used with caution in:
– Pregnancy.
– Epilepsy.
– Parkinsonism.
– Renal failure.
– In elderly patients.

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.

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: benign pituitary tumor, such as prolactinoma. Metabolic and nutritional disorders

Often: weight gain.

Infrequent: hyperglycemia (see sections “Caution” and “Cautionary Note”), 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 per day. According to data from clinical studies, there was a significantly lower incidence of extrapyramidal symptoms with amisulpride than with haloperidol.

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 increase the symptomatology); seizures.

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

Frequency unknown: restless legs syndrome with or without akathisia.

Visual disturbances

Often: blurred vision.

Heart disorders

Infrequent: bradycardia.

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

Vascular disorders

Chasmo: decrease of blood pressure.

Infrequent: increase of blood pressure.

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

Respiratory, chest and mediastinal disorders

Infrequently: Nasal congestion; aspiration pneumonia (mainly when used concomitantly with other antipsychotics and CNS depressants).

Gastrointestinal disorders

Often: constipation, nausea, vomiting, dry mouth. .

Disorders of the liver and biliary tract

Infrequent: hepatocellular lesions.

Skin and subcutaneous tissue disorders

Rarely: angioedema, urticaria.

Prevalence unknown: photosensitization.

Muscle and connective tissue disorders

Infrequent: osteopenia, osteoporosis.

Renal and urinary tract disorders

Infrequent: urinary retention.

Injuries, complications and complications due to manipulation

Frequency unknown: Falls (sometimes resulting in fractures) as a consequence of developing adverse reactions related to possible balance problems.

Pregnancy, postpartum and perinatal conditions

Frequency unknown: “withdrawal” syndrome in newborns (see “Use in pregnancy and during breastfeeding”).

Laboratory disorders

Infrequent: increase of 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 use in pregnancy has not been established.

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

The use of amisulpride during lactation is contraindicated.