Instructions for use Sonapax 25 mg film-coated tablets 25 mg blister No. 60
Composition
active ingredient: thioridazine hydrochloride;
1 film-coated tablet contains: thioridazine hydrochloride 10 mg or 25 mg;
excipients: film-coated tablets, 10 mg: corn starch, colloidal anhydrous silica, sucrose, lactose monohydrate, gelatin, stearic acid, talc, gum arabic (E 414), cochineal red A (E 124);
film-coated tablets, 25 mg: potato starch, sucrose, gelatin, gum arabic (E 414), magnesium stearate, sucrose, talc, quinoline yellow (E 104).
Dosage form
Film-coated tablets.
Main physicochemical properties:
Sonapax ® 10 mg tablets are round, biconvex, film-coated tablets of light pink color, uniform in color. White when broken.
Sonapax ® 25 mg tablets are round, biconvex, film-coated tablets of light yellow color, uniform in color. White on the break.
Pharmacotherapeutic group
Antipsychotics. Piperidine derivatives of phenothiazines. ATX code N05A C02.
Pharmacological properties
Pharmacodynamics
Thioridazine belongs to the group of neuroleptics. It is a piperidine derivative of phenothiazine, which significantly affects the nervous system, both central and peripheral. It has a depressing effect mainly on the brainstem, to a lesser extent - on the cerebral cortex. Peripherally it has α-adrenolytic, antihistamine and cholinolytic effects, which are the most pronounced among all neuroleptics. It does not cause antiemetic effects, causes fewer extrapyramidal disorders than other neuroleptics. It does not suppress intrinsic motor activity.
Thioridazine has all the characteristic neuroleptic properties: it has a weak antipsychotic, antiautistic, and weak antidepressant effect; it does not have an activating effect.
Pharmacokinetics
Thioridazine is absorbed rapidly and completely from the gastrointestinal tract, reaching peak blood concentrations in 2-4 hours. About 95% of the drug is bound to plasma proteins. The elimination half-life is 1 hour.
Thioridazine is metabolized in the liver. 35% is excreted in the urine, the rest in the feces (unchanged and in the form of metabolites). It penetrates the placental barrier and into breast milk.
Indication
Mental and emotional disorders accompanied by fear, anxiety, and excitement.
In psychiatric practice: acute and subacute schizophrenia, organic psychoses, psychomotor agitation, manic-depressive states, neuroses, alcohol withdrawal syndrome, mental behavioral disorders in children, excited state in elderly patients.
Contraindication
Hypersensitivity to phenothiazine derivatives or to any component of the drug.
Thioridazine is contraindicated in patients with the following conditions: clinically significant cardiac disorders (heart failure, angina, cardiomyopathy or left ventricular dysfunction) - long QTc syndrome, family history of long QTc syndrome. Since thioridazine prolongs the QTc interval, it is also contraindicated with concurrent use of drugs that also prolong the QTc interval. Ventricular arrhythmia, including a history, bradycardia, SA or second or third degree atrioventricular block, uncorrected hypokalemia or hypomagnesemia. History of cardiac arrhythmia, severe arterial hypotension, pheochromocytoma, porphyria, blood diseases (hypo- and aplastic processes), simultaneous use with fluoxetine, paroxetine, propranolol, pindolol, fluvoxamine, genetic disorders leading to a decrease in the level of P450 2D6 activity.
Severe photosensitivity, severe depressive states, comatose states of any etiology, dementia, traumatic brain injuries, progressive systemic diseases of the brain and spinal cord.
Interaction with other medicinal products and other types of interactions
When used simultaneously, it exhibits a synergistic effect with general anesthetics, opiates, barbiturates, ethanol, and atropine.
When used simultaneously, it increases the hepatotoxic effect of antidiabetic drugs.
When used simultaneously with amphetamine, it has an antagonistic effect.
When used simultaneously with levodopa, it weakens its anti-Parkinsonian effect.
Concomitant use with adrenaline may lead to a sudden and significant decrease in blood pressure.
When used simultaneously with guanethidine, it reduces the hypotensive effect of the latter, but enhances the effect of other antihypertensive drugs, which increases the risk of orthostatic hypotension.
Antithyroid drugs increase the risk of developing agranulocytosis.
Quinidine potentiates the cardiodepressive effect of the drug.
Ephedrine contributes to an abnormal decrease in blood pressure.
Sympathomimetics – increase the arrhythmogenic effect.
Reduces the effects of appetite suppressants (except fenfluramine).
Reduces the effectiveness of the emetic effect of apomorphine, increases its inhibitory effect on the CNS.
Increases the concentration of prolactin in blood plasma and reduces the effectiveness of bromocriptine.
When used simultaneously with thiazide diuretics, increased hyponatremia is possible;
with lithium preparations - lower absorption in the gastrointestinal tract, accelerated excretion of lithium ions by the kidneys, increased manifestations of extrapyramidal disorders. Early signs of lithium intoxication (nausea and vomiting) may be masked by the antiemetic effect of thioridazine.
When used simultaneously with beta-blockers, it enhances the hypotensive effect.
Pharmacokinetic interactions.
Probucol, astemizole, cisapride, disopyramide, erythromycin, pimozide, procainamide, and quinidine prolong the QTS interval, which increases the risk of ventricular tachycardia.
Cytochrome P450 2D6 metabolism.
Thioridazine is metabolized by cytochrome P450 2D6 and is an inhibitor of the enzyme that metabolizes the drug. The plasma concentration and efficacy of thioridazine may be increased and prolonged by drugs that are substrates and/or inhibitors of the P450 isoform, which may result in severe hypotension, cardiac arrhythmias, or CNS side effects. Examples of drugs that are substrates or inhibitors of cytochrome P450 2D6, including antiarrhythmic drugs, include some antidepressants, including SSRIs and tricyclics, some neuroleptics, β-blockers, protease inhibitors, opiates, and "ecstasy" (MDMA).
Antiepileptic drugs.
Phenytoin serum levels may be increased or decreased by thioridazine, and dosage adjustments may be necessary. No effect on serum levels of thioridazine or carbamazepine has been observed when carbamazepine is coadministered with thioridazine.
Barbiturates
The contaminating effect of phenothiazines reduces the serum levels of both drugs, and also eliminates the possibility of an increase in the serum levels of one of these drugs.
Antihypertensive drugs and β-blockers
In combination with other phenothiazines, thioridazine antagonizes adrenaline and other sympathomimetic agents. Since β-blockers are substrates of cytochrome P450 2D6, they may cause bradycardia. Concomitant use of thioridazine with β-blockers is not recommended. In addition, thioridazine may block the blood pressure-lowering effects of adrenergic blocking agents, including guanethidine and clonidine.
Anticoagulants.
Concomitant treatment with phenothiazines may increase the effect of anticoagulants. Pharmacodynamic interactions.
The effect of thioridazine on the QTc interval may be potentiated by concomitant use of other drugs that also prolong the QTc interval. Therefore, concomitant use of these drugs and thioridazine is contraindicated. Examples include certain antiarrhythmic drugs, particularly those of class IA (e.g. quinidine, disopyramide and procainamide) and class III (e.g. amiodarone and sotalol), tricyclic antidepressants (e.g. amitriptyline), and some of the tetracyclic antidepressants (e.g. meprotiline); certain antipsychotics (e.g. phenothiazines and pimozide) and certain antihistamines (e.g. terfenadine), lithium preparations, quinine, pentamidine and sparfloxacin.
Electrolyte imbalance, particularly hypokalemia, significantly increases the risk of QTc prolongation. Therefore, concomitant use of drugs that cause electrolyte imbalance should be avoided.
CNS depressants
Thioridazine may enhance central nervous system depression caused by other CNS depressants such as narcotics, alcohol, sedatives, and narcotic analgesics.
MAO inhibitors
Concomitant use may increase sedation, constipation, dry mouth, and hypotension.
Lithium
Serious complications, neurotoxic extrapyramidal side effects, and episodes of sleepwalking have been described in patients receiving concomitant lithium and phenothiazines, including thioridazine.
Anticholinergics
Undesirable anticholinergic effects may occur with the concomitant use of anticholinergic drugs and thioridazine. In any case, close supervision and dosage adjustment are required when used concomitantly with agents such as antihistamines, tricyclic antidepressants and atropine-containing compounds.
Antiparkinsonian drugs
The effectiveness of both drugs may be reduced when these drugs are used concomitantly with thioridazine.
Adrenergic vasoconstrictors
Due to its blood pressure-lowering ability, phenothiazines may reduce the vasopressor activity of adrenergic vasoconstrictors (e.g., ephedrine, phenylephrine).
Phenylpropanolamine
There have been reports that ventricular arrhythmias may occur with the simultaneous use of phenylpropanolamine and thioridazine.
Thiazide diuretics
Concomitant use of phenothiazines and thiazide diuretics may result in severe hypotension and diuretic-induced hypokalemia, which may potentiate thioridazine-induced cardiotoxicity.
Antacids, antidiarrheals
These drugs may reduce the gastrointestinal absorption of orally administered phenothiazines. Antacids should not be used within 2 hours of taking phenothiazines.
Antidiabetic drugs
Phenothiazine affects carbohydrate metabolism and therefore interferes with blood sugar control in diabetic patients.
Application features
QT prolongation: Due to the risk of arrhythmias due to QT prolongation, thioridazine should only be used after assessment of the risk factor for QT prolongation in patients who have undergone ECG and have an average acceptable serum potassium concentration. Patients with an average QTc interval (500 ms) should not be prescribed thioridazine. During treatment with Sonapax, serum electrolytes should be monitored periodically and possible electrolyte abnormalities should be corrected. Concomitant treatment should be carefully evaluated in the case of the use of drugs that inhibit CYP 2D6, inhibit the metabolism of thioridazine by other pathways, or lead to QT prolongation. The use of thioridazine is contraindicated with such drugs. Caution should be exercised if the patient is taking drugs that can lead to hypokalemia.
Because thioridazine is metabolized by CYP 2D6, patients who are poor metabolizers of this enzyme are also at increased risk for QT prolongation. Slower metabolism may be expected in some patients based on experience with other agents metabolized by CYP 2D6. Methods for testing for poor metabolizers are not widely available. Patients known to be poor metabolizers should not be given thioridazine.
Anticholinergic properties: Due to its known anticholinergic properties, thioridazine should be used with caution in patients with increased intraocular pressure, glaucoma, urinary retention (e.g., prostatic hypertrophy), and chronic constipation.
Liver disease: Patients with liver disease require regular monitoring of liver function.
Blood dyscrasias: Even though only rare cases of leukopenia or agranulocytosis have been reported, blood tests should be performed regularly during the first 3-4 months of treatment. If clinical signs of dyscrasia appear, blood tests should be performed immediately.
Blood pressure: Orthostatic hypotension is common in patients taking thioridazine. After starting treatment with thioridazine, it is advisable to check blood pressure, especially in elderly patients with orthostatic hypotension or with labile circulation.
Alcohol: Since alcohol may increase the risk of hepatotoxic reactions, heat stroke, akathisia, dystonia or other central nervous system disorders, its use should be avoided during treatment with thioridazine.
Tolerance: Tolerance to the sedative effects of phenothiazines and cross-tolerance to antipsychotics have been reported. Tolerance may also increase the risk of clinical withdrawal symptoms.
Neuroleptic malignant syndrome.
When using neuroleptics, neuroleptic malignant syndrome was observed, the clinical manifestations of which are hyperpyrexia, muscle rigidity, impaired thinking, consciousness, autonomic disorders (arrhythmic pulse, changes in blood pressure, tachycardia, diaphoresis, cardiac arrhythmia). Diagnosis of this syndrome is complicated. When establishing this diagnosis, it is important to consider such serious diseases as pneumonia, systemic infections, inadequate treatment of extrapyramidal disorders, symptoms of toxicity of anticholinergic drugs, heart attacks, drug fever, primary pathology of the central nervous system. Treatment of neuroleptic malignant syndrome includes immediate discontinuation of neuroleptics, intensive care, treatment of concomitant diseases. There is no specific treatment. Neuroleptics should be taken with caution if their further use is necessary.
Central nervous system depression.
The drug should be prescribed with caution in alcoholism (propensity to hepatotoxic reactions), breast cancer (due to phenothiazide-induced prolactin secretion, the potential risk of disease progression and resistance to treatment with endocrine and cytotoxic drugs increases), in hepatic and/or renal failure, gastric and duodenal ulcer during the exacerbation period; in diseases accompanied by an increased risk of thromboembolic complications, Parkinson's disease (extrapyramidal effects are enhanced); in epilepsy; myxedema; in chronic diseases accompanied by respiratory disorders (especially in children); Reye's syndrome (increased risk of hepatotoxicity in children); with cachexia, vomiting (the antiemetic effect of phenothiazine may mask vomiting associated with an overdose of other drugs), the elderly, patients with cardiac arrhythmias, heart disease, myasthenia gravis, epilepsy. In case of liver disease, regular monitoring of its functions is necessary. When treating patients with schizophrenia and a history of seizures, anticonvulsant therapy should be used simultaneously with thioridazine. When using thioridazine in doses higher than recommended, pigmentary retinopathy may occur, characterized by decreased visual acuity and impaired night vision, and changes in color perception. In these cases, the dose should be reduced. Orthostatic hypotension occurs more often in women than in men.
Epinephrine should be avoided for the treatment of drug-induced hypotension because phenothiazines may cause the opposite effect. If vasoconstrictors are necessary, levarterenol and phenylephrine are recommended. Neuroleptics increase prolactin levels in the blood with chronic use. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported. Alcohol should not be consumed during treatment, and sun exposure should be limited.
Patients with a history of symptoms that may be indicative of torsade de pointes (dizziness, palpitations, syncope) should have ECG monitoring, including Holter monitoring.
When prescribing neuroleptics, the occurrence of tardive dyskinesia should be minimized if possible. With long-term use of neuroleptics, the response to treatment should be taken into account, if necessary, alternative, less toxic drugs should be used; neuroleptics should be used in a lower dose or in short courses.
When establishing the diagnosis of "neuroleptic malignant syndrome", it is important to consider such serious diseases as pneumonia, systemic infections, inappropriate treatment of extrapyramidal disorders, symptoms of anticholinergic toxicity, heart attacks, drug fever, primary pathology of the central nervous system. Treatment of neuroleptic malignant syndrome includes immediate discontinuation of neuroleptics, intensive care, treatment of concomitant diseases. There is no specific treatment. Neuroleptics should be taken with caution if their continued use is necessary.
Use during pregnancy or breastfeeding
The effect of thioridazine on the fetus is unknown.
Do not use the drug during pregnancy.
Breastfeeding should be discontinued during treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
Thioridazine impairs coordination of movements and reduces the ability to react, especially at the beginning of treatment. During therapy, patients should not drive vehicles or other mechanisms.
Method of administration and doses
The dose is set individually by the doctor, the lowest therapeutically effective dose should be determined for each patient individually. The daily dose should be divided into 2-4 doses.
Adults and teenagers.
Mental and emotional disorders such as schizophrenia, manic psychosis and similar conditions: 150-600 mg per day. The initial dose may be increased to 200 mg for patients with acute schizophrenia. The daily dose may be increased to 800 mg in resistant patients under medical supervision, but not for more than 4 weeks.
Treatment of psychosis in outpatient settings: daily dose ˗50-300 mg, patients with depression and elderly patients - 25-200 mg, alcohol withdrawal syndrome - 100-200 mg, severe mental disorders of a non-psychotic nature - 25-150 mg. As a sedative and tranquilizer, Sonapax ® is prescribed to adults in a daily dose of 10-75 mg.
Usual doses for use in pediatrics.
Children aged 5-12 years: 0.25-3 mg per 1 kg of body weight per day, divided into 2-4 doses. Severe disorders: 25 mg 2-3 times a day. Maximum daily dose - 300 mg. At a dosage not multiple of 25 mg, thioridazine should be used in appropriate dosage forms and dosages.
Children
Do not use in children under 5 years of age.
Overdose
Symptoms of overdose, including symptoms of phenothiazine overdose:
from the nervous system: mydriasis, miosis, dry skin, dry mouth, hyperemia of the nasal mucosa, nasal congestion, urinary retention, visual impairment, speech impairment, drowsiness, impaired consciousness, orientation, visual acuity, excitation, motor hyperactivity, extrapyramidal symptoms, convulsions, coma, agitation, hypothermia, hyperthermia, insomnia, areflexia;
from the respiratory system: respiratory depression, apnea, pulmonary edema;
from the digestive tract: decreased peristalsis, constipation, ileus, paralytic ileus, nausea, vomiting;
From the urinary system: oliguria, uremia. The toxic dose and blood concentration of phenothiazines have not been accurately estimated.
Treatment: gastric lavage with activated charcoal. Ensuring airway patency, monitoring of the cardiovascular system and ECG for arrhythmia; correction of electrolyte levels, acid-base balance, use of lidocaine, phenytoin, isoproterenol, defibrillation. Avoid the use of disopyramide, procainamide, quinidine, since they, like thioridazine, prolong the QT interval (see sections "Special instructions" and "Contraindications"). Caution should be exercised when using lidocaine, since it increases the risk of seizures.
To treat arterial hypotension, use intravenous administration of solutions and vasoconstrictor drugs (to treat refractory hypotension, use phenylephrine, levarterinol or metaraminol, as well as epinephrine and dopamine).
Treatment is aimed at reducing absorption and accelerating the elimination of the drug.
Vomiting should not be induced, given the risk of dystonia and aspiration of vomit.
For the treatment of acute extrapyramidal symptoms, use diphenhydramine hydrochloride or benztropine mesylate.
Barbiturates should be avoided for the treatment of seizures because they potentiate the respiratory depression caused by phenothiazines.
Forced diuresis, hemoperfusion, and hemodialysis are ineffective because the drug binds to blood proteins.
Adverse reactions
From the nervous system and sensory organs: drowsiness, inhibition, especially when taking high doses at the beginning of treatment, which usually disappears with further treatment or when the dose is reduced; pseudoparkinsonism with other extrapyramidal symptoms, confusion, hyperactivity, lethargy, psychotic reactions, emotional instability, headache, insomnia, emotional disorders, thermoregulation disorders, decreased seizure threshold, fainting, blurred vision, nasal congestion, pallor, miosis, yawning, emotional excitement, visual impairment.
On the part of the endocrine system: galactorrhea, breast enlargement, edema.
From the cardiovascular system:
hypotension, tachycardia, palpitations, QT prolongation, which may lead to the development of torsade de pointes arrhythmia, polymorphic ventricular tachycardia and sudden death (see "Special warnings and precautions for use"), other ECG changes (QT prolongation, depression or inversion of the T wave, bifurcation of the T wave or
U). These changes are reversible, occur as a result of changes in repolarization, and are not related to myocardial damage. QT prolongation has been associated with severe ventricular arrhythmias and sudden death; hypotension has been reported as a result of myocardial infarction.
On the part of the digestive tract: hyposalivation, increased appetite, dyspepsia, weight gain, hypertrophy of the tongue papillae, dry mouth, nausea, vomiting, diarrhea, constipation, anorexia, paralytic ileus.
Skin: skin rashes, erythema, urticaria, exfoliative dermatitis, contact dermatitis, skin melanosis (with prolonged use in high doses), photosensitivity reactions.
From the blood system: agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, anemia, aplastic anemia, pancytopenia, granulocytopenia.
Allergic reactions: fever, laryngeal edema, angioedema, bronchospastic syndrome, nasal congestion, asthma, allergic skin reactions.
From the hepatobiliary system: cholestatic jaundice, bile stasis.
On the part of the psyche: akathisia, agitation, motor excitement, dystonic reactions, trismus, torticollis, opisthotonus, oculogyric crises, tremor, muscle rigidity, akinesia.
Neuroleptic malignant syndrome: long-term use of antipsychotic drugs is associated with the development of neuroleptic malignant syndrome, the clinical manifestations of which are hyperpyrexia, muscle rigidity, impaired thinking, consciousness, autonomic disorders (arrhythmic pulse, changes in blood pressure, tachycardia, diaphoresis, cardiac arrhythmia).
From the reproductive system: menstrual cycle disorders, changes in libido, gynecomastia, lactation, weight gain, edema, false-positive pregnancy tests.
From the genitourinary system: urinary retention, urinary incontinence, decreased libido, ejaculation disorders, dysmenorrhea, hyperprolactinemia, gynecomastia, paradoxical ischuria, dysuria, priapism.
Other: hyperpyrexia, rare attacks of salivary gland edema, priapism. Paradoxical reactions, behavioral disorders including agitation, increased psychosis, impaired consciousness due to toxic effects, progressive pigmentation of the skin or conjunctiva with or without discoloration of the sclera and cornea, opacity of the anterior surface of the lens of the eye, systemic lupus erythematosus have been reported.
The occurrence of adverse reactions observed with phenothiazine derivatives is not excluded. The most common neurological disorders are parkinsonism and akathisia, as well as an increased risk of agranulocytosis and leukopenia in elderly patients.
Expiration date
4 years.
Storage conditions
Store in a dry place at a temperature not exceeding 25 °C.
Packaging
For 10 mg film-coated tablets: 30 tablets in a blister, 2 blisters together with instructions for medical use are placed in a cardboard box;
for 25 mg film-coated tablets: 20 tablets in a blister, 3 blisters together with instructions for medical use are placed in a cardboard box.
Vacation category
According to the recipe.
Producer
Pharmaceutical factory Elfa A.T., Poland.
Location of the manufacturer and its business address
58-500 m. Jelenia Góra, 21 Vincentiego Pola Street, Poland.
58-500 Jelenia Góra, str. Wincentego Pola, 21, Poland
