Sonapaks 10 mg of the tab. of p/o of 10 mg No. 60

Pharmacological properties

Pharmacodynamics. thioridazine belongs to group of neuroleptics and is to piperidinovy derivatives of a fenotiazin. it significantly influences both central, and peripheral nervous system. has the oppressing effect generally on a brainstem, to a lesser extent — on a cerebral cortex. peripheral action is connected with α-adrenolytic, antihistaminic and cholinolytic action which is more significant in comparison with other neuroleptics. has no antiemetic properties, causes development of extrapyramidal disturbances, than other neuroleptics less often. does not oppress internal motor activity.

Thioridazine has all properties, characteristic of neuroleptics: renders weak antipsychotic, antiautichesky and weak antidepressive action; does not show the activating effect.

Pharmacokinetics. Thioridazine is quickly and completely soaked up in a GIT, reaching the C _max in blood through 2–4 h after reception. About 95% of thioridazine contact proteins of blood plasma. The t _½ makes 10 h

Thioridazine is metabolized in a liver. About 35% are removed with urine, other quantity — with a stake (in not changed look and in the form of metabolites). Gets through a placental barrier and into breast milk.

Indication

Mental and emotional disturbances which are followed by fear, alarm, excitement.

In psychiatric practice — acute and subacute schizophrenia, a pathopsyhosis, psychomotor excitement, manic-depressive states, neurosises, a syndrome of alcoholic abstinency, mental disorders of behavior of children, the excited state at elderly people.

Use

Dose is established by the doctor individually, the effective dose minimum therapeutic is defined for each patient separately. the daily dose is distributed on 2–4 receptions.

Adults and teenagers. Mental and emotional disturbances, such as schizophrenia, maniacal psychoses and similar states: 150–600 mg/days. The initial dose can be raised to 200 mg for patients with acute schizophrenia. The daily dose can be raised to 800 mg at resistant patients under control of the doctor, but no more than for 4 weeks

Treatment of psychosis in out-patient conditions: a daily dose — 50–300 mg, to patients with a depression and to patients of advanced age — 25–200 mg, a syndrome of alcoholic abstinency — 100–200 mg, heavy disturbances of mentality of not psychotic character — 25–150 mg. As sedative and Sonapaks tranquilizer are appointed the adult in a daily dose of 10-75 mg.

Usual doses for use in pediatrics. To children at the age of 5–12 years: 0.25-3 mg/kg of body weight the day distributed on 2–4 receptions. Heavy disorders: on 25 mg 2–3 times a day. The maximum daily dose — 300 mg. When dosing, not multiple 25 mg, it is necessary to apply thioridazine in the corresponding dosage forms and dosages.

Contraindication

Hypersensitivity to derivatives of a fenotiazin or to any component of drug.

Thioridazine is contraindicated to patients with such states: clinically important disturbances of heart (heart failure, stenocardia, cardiomyopathy or dysfunction of a left ventricle): a syndrome of the extended Q–Tc interval, the family anamnesis of a syndrome of the extended Q–Tc interval. As thioridazine extends Q–Tc interval, it is also contraindicated at competitive use of the medicaments also capable to extend this interval. Ventricular arrhythmia, including in the anamnesis, bradycardia, sinuatrial or atrioventricular block of II and III degree, not corrected hypopotassemia or a hypomagnesiemia. Cardiac arrhythmia in the anamnesis, heavy arterial hypotension, a pheochromocytoma, a porphyria, a blood disease (hypo - and aplastic processes), simultaneous use with fluoxetine, paroksetiny, propranolol, Pindololum, fluvoksaminy, genetic disorders which lead to decrease in level of activity of P450 2D6.

Heavy photosensitivity. Heavy depressions, comas of any etiology, dementia, craniocereberal injuries, the progressing general diseases of a head and spinal cord. Period of pregnancy and feeding by a breast. Children's age of 5 years.

Side effects

from nervous system and sense bodys: drowsiness, block, especially at reception in high doses in an initiation of treatment, usually disappearing at further treatment or a dose decline; a pseudoparkinsonism with other extrapyramidal symptoms, confusion of consciousness, hyperactivity, a lethargy, psychotic reactions, excitement, a headache, insomnia, emotional disturbances, thermal control disturbance, decrease in a convulsive threshold, unconsciousness, a sight zatumanennost, congestion of a nose, pallor of integuments, a miosis, yawning.

from an endocrine system: galactorrhoea, increase in mammary glands, hypostases.

from a cardiovascular system: arterial hypotension, tachycardia, heart consciousness, lengthening of an interval of Q-Tc that can serve as the reason of development of arrhythmia as torsade de pointes, polymorphic ventricular tachycardia and a sudden lethal outcome (see. Special INSTRUCTIONS), other changes of the ECG (lengthening of an interval of Q-Tc, depression or inversion of a tooth of T, bifurcation of a tooth of T or U). These changes are reversible, arise owing to repolarization change, have no relation to injury of a myocardium. Lengthening of an interval of Q-Tc is connected with heavy ventricular arrhythmia and a sudden lethal outcome; it was reported about arterial hypotension as a result of heart attack.

from a GIT: increase in appetite, dyspepsia, increase in body weight, a hypertrophy of nipples of language, dryness in a mouth, nausea, vomiting, diarrhea, a constipation, anorexia, paralytic intestinal impassability.

from skin: skin rash, an erythema, a small tortoiseshell, exfoliative dermatitis, contact dermatitis, a skin melanosis (at prolonged use in high doses), reactions of photosensitivity.

from the system of blood: agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, anemia, aplastic anemia, pancytopenia.

Allergic reactions: fever, laryngeal edema, Quincke's disease, bronkhospastichesky syndrome, congestion of a nose, OH.

from a gepatobiliarny system: cholestatic jaundice, stagnation of bile.

from mentality: akathisia, agitation, motive excitement, dystonic reactions, lockjaw, wryneck, opisthotonos, okulogirny crises, tremor, muscle tension, akineziya.

Late dyskinesia: long use of antipsychotic means can lead to appearance of dyskinesia of this type. This syndrome is characterized by involuntary chaotic movements, including movements of language, a face, mouth, lips, jaws (protrusion of language, inflation of cheeks, wrinkling of a mouth, chewing movements), the movements of a face, extremities. Weight of a syndrome and a damage rate change. The syndrome can arise during treatment, at change of a dose or the termination of treatment. It is important to diagnose these symptoms as soon as possible. The expressiveness of movements can decrease and even to disappear if to stop intake of antipsychotic medicines. The reversibility of reactions is more significant at a short course of treatment, than at long reception. It is important to diagnose this syndrome quickly. It is necessary to watch a condition of the patient, at an opportunity it is necessary to reduce a dose of antipsychotic drugs. It is necessary to consider that antipsychotic medicines mask symptoms of this syndrome.

Malignant antipsychotic syndrome: long use of antipsychotic medicaments is connected with development of a malignant antipsychotic syndrome which clinical manifestations are the hyper pyrexia, muscle tension, disturbance of thinking, consciousness, vegetative disorders (arrhythmic pulse, change of the ABP, tachycardia, diaforez, heart arrhythmia).

from a reproductive system: disturbance of a menstrual cycle, change libido, gynecomastia, lactation, increase in body weight, hypostases, false positive tests for pregnancy.

from an urinogenital system: urination delay, urine incontinence, decrease in a libido, disturbance of an ejaculation, dysmenorrhea, giperprolaktinemiya, gynecomastia, inconscience with overflow, dysuria, priapism.

Others: a hyper pyrexia, it is very rare — cases of hypostasis of sialadens, a priapism. It was reported about the paradoxical reaction, behavioural disorders including excitement, strengthening of psychosis, unusual dreams, disturbance of consciousness owing to toxic influence, the progressing xanthopathy or conjunctivas with or without discoloration of a sclera and a cornea, opacity of a front surface of a lens, a system lupus erythematosus.

did not exclude emergence of side reactions which note at reception of derivatives of a fenotiazin. The most frequent neurologic disorders are parkinsonism and an akathisia and also the increased risk of appearance of an agranulocytosis and a leukopenia at elderly people.

Special instructions

Lengthening of an interval of q-tc: in connection with risk of developing arrhythmias owing to lengthening of an interval of q-tc thioridazine should be applied only after risk assessment of lengthening of an interval of q-tc at those patients to whom the ECG is carried out and the average acceptable level of potassium concentration in blood serum is determined. to patients with the average level of an interval of q-tc of 500 ms thioridazine is not appointed. abnormal level of content of potassium in blood serum should be determined before prescribing of thioridazine.

Accompanying therapy needs to be estimated carefully in case of use of medicaments which brake CYP 2D6, thioridazine metabolism in other ways or lead to lengthening of an interval of Q-Tc. Simultaneous use of thioridazine is contraindicated with medicaments of this action. It is necessary to be careful if the patient takes the medicament which can lead to a hypopotassemia.

As thioridazine is metabolized by CYP 2D6, patients at whom metabolism process by this enzyme takes place slowly, are also exposed to the increased risk of lengthening of an interval of Q-Tc. It is possible to expect delay of process of metabolism at some patients on the basis of experience of use of other agents who are metabolized by CYP 2D6. The algorithm of check of a possibility of slow metabolism did not become widespread. To patients for whom the fact of slow metabolism is already known thioridazine is not appointed.

Anticholinergic properties: in connection with the known anticholinergic properties thioridazine is appointed with care to patients with the increased intraocular pressure, glaucoma, an ischuria (for example a prostatauxe) and a chronic constipation.

liver Disease: regular control of functions of a liver is necessary for patients with diseases of a liver.

blood Dyscrasia: even if the rare occurences of a leukopenia or an agranulocytosis were registered, blood test needs to be carried out regularly for the first 3–4 months of treatment. If clinical signs of a dyscrasia are noted, then blood test needs to be carried out immediately.

ABP: often note orthostatic hypotension at patients who accept thioridazine. After an initiation of treatment thioridazine it is reasonable to check the ABP, especially at elderly people with orthostatic arterial hypotension or labile blood circulation.

Alcohol: alcohol can exponentiate risk of hepatotoxic reaction, heatstroke, an akathisia, dystonia or other disorders of central nervous system, its use throughout treatment by thioridazine it is necessary to avoid.

Tolerance: tolerance cases to sedative action of a fenotiazin and cross tolerance to antipsychotic means were revealed. The tolerance can also cause increase in risk of emergence of the clinical phenomenon of abstinency.

Malignant antipsychotic syndrome. At use of neuroleptics noted a malignant antipsychotic syndrome which clinical manifestations are the hyper pyrexia, muscle tension, disturbance of thinking, consciousness, vegetative disorders (arrhythmic pulse, change of the ABP, tachycardia, diaforez, heart arrhythmia). Diagnostic assessment of this syndrome is complicated. At establishment of this diagnosis it is important to consider such serious diseases as pneumonia, system infections, inappropriate treatment of extrapyramidal disorders, symptoms of toxicity of anticholinergics, heart attacks, medicamentous fever, primary pathology of central nervous system. Treatment of a malignant antipsychotic syndrome includes immediate phase-out of neuroleptics, intensive treatment, therapy of associated diseases. Specific treatment is absent. If there is a need for reception of neuroleptics, it is necessary to apply them with care.

Oppression of central nervous system. As well as other fenotiazina, thioridazine it is capable to strengthen effect of the medicines suppressing central nervous system (alcohol, anesthetics, barbiturates, drugs, opiates, other psychoactive substances) and also atropine, phosphorus drugs. At simultaneous use of barbiturates in high doses there can be respiratory depression.

With care appoint medicament in alcoholism (tendency to hepatotoxic reactions), a breast cancer (owing to the secretion of prolactin induced fenotiaziny the potential risk of progressing of a disease and resistance to treatment by endocrine and cytotoxic medicaments increases), a liver and/or renal failure, a peptic ulcer of a stomach and a duodenum during aggravation; the diseases which are followed by the increased risk of tromboembolic episodes, Parkinson's disease (extrapyramidal effects amplify); epilepsies; to a myxedema; the chronic diseases which are followed by breath disturbance (especially at children); a syndrome to Reja (increase in risk of development of hepatotoxicity at children); to a cachexia, vomiting (antiemetic action of a fenotiazin can mask the vomiting connected with overdose of other drugs), at elderly people, patients with disturbances of a warm rhythm, heart diseases, a myasthenia, epilepsy. In a disease of a liver the regular control of its functions is necessary. At treatment of patients with schizophrenia or spasms in the anamnesis along with thioridazine apply anticonvulsants. At use of thioridazine in doses above recommended there can be a pigmentarny retinopathy which is characterized by decrease in visual acuity, a disorder of vision at night, change of color perception. In these cases the dose is reduced. Orthostatic hypotension arises more often at women, than at men.

Should avoid use of epinephrine for treatment of medicamentous hypotension, considering that fenotiazina can provoke retroaction development. In need of use of vasoconstrictors it is recommended to apply levarterenol and Phenylephrinum. Neuroleptics at chronic use increase prolactin level in blood plasma. It was reported about development of a galactorrhoea, amenorrhea, gynecomastia and impotence. During treatment not to take alcohol, to limit stay in the sun.

At patients in whose anamnesis there were symptoms of manifestation of torsade de pointes (dizziness, heart consciousness, a syncope) ECG monitoring including holterovsky monitoring.

Appointing neuroleptics, it is necessary to minimize risk of developing of late dyskinesia. At long use of neuroleptics it is necessary to consider the response to treatment, if necessary — to perform alternative therapy, to apply less toxic drugs, neuroleptics in the lowest dose or short courses.

At establishment of the diagnosis of a malignant antipsychotic syndrome it is important to p to consider such serious diseases as pneumonia, system infections, inappropriate treatment of extrapyramidal disorders, symptoms of toxicity of anticholinergic medicines, heart attacks, medicamentous fever, primary pathology of central nervous system. Treatment of a malignant antipsychotic syndrome includes immediate phase-out of neuroleptics, intensive treatment, treatment of associated diseases. There is no specific therapy. It is necessary to apply with care neuroleptics in case of need of their further reception.

Use during pregnancy and feeding by a breast. During pregnancy medicament is not used. During treatment it is necessary to stop feeding by a breast.

Children. Do not apply at children at the age of 5 years.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Thioridazine worsens coordination and reduces a possibility of quick response, especially in an initiation of treatment. Throughout treatment the patients cannot run vehicles or to work with other mechanisms.

Interaction

Pharmacokinetic interactions

Metabolism of P450 2D6 cytochrome. Thioridazine is metabolized by P450 2D6 cytochrome and at the same time is inhibitor of metabolizing enzyme of drug. Concentration in blood plasma and efficiency of thioridazine can be raised and prolonged by medicaments which are substrates and/or inhibitors of P450 isoform that can lead to heavy hypotension, disturbance of a warm rhythm or side effects from central nervous system. The medicaments which are substrates or inhibitors of P450 2D6 cytochrome including antiarrhytmic drugs, some antidepressants, including inhibitors of the return serotonin reuptake and tricyclic connections, some neuroleptics, blockers of β-adrenoceptors, inhibitors of proteases, opiates and ecstasy (MDMA).

Anti-epileptic drugs. Under the influence of thioridazine Phenytoinum level in blood serum can be there is raised or reduced and can be a need for dose adjustment. It was not established influences on the level of thioridazine or carbamazepine in blood serum in interaction with carbamazepine.

Barbiturates. Kontaminiruyushchy action of finotiazin reduces the level of both medicaments in blood serum and excludes a possibility of increase in level of one of them in blood serum.

Antihypertensive medicaments and blockers of β-adrenoceptors. Together with other fenotiazina, thioridazine shows antagonism to adrenaline and other sympathomimetic agents. As blockers of β-adrenoceptors are substrates of P450 2D6 cytochrome, they can cause bradycardia. Simultaneous use of thioridazine with blockers of β-adrenoceptors is not recommended. Besides, thioridazine can block action of adrenergic blockers which lower the arterial blood pressure and which treat guanetidin and a clonidine.

Anticoagulants. Simultaneous treatment from fenotiazina can cause increase in expressiveness of effect of anticoagulants probably in connection with competitive inhibition (exact control of an indicator of INR is necessary).

Influence of thioridazine on an interval of Q-Tc can be increased by

at simultaneous use of other medicaments which also extend Q–Tc interval. Thus, simultaneous use of these medicaments and thioridazine is contraindicated. For example, antiarrhytmic medicaments IA of a class, such as quinidine, Disopyramidum and procaineamide, and the III class (Amiodaronum and sotalol), tricyclic antidepressants (for example amitriptyline) and also some tetracyclic antidepressants, such as Maprotilinum; some antipsychotic drugs, for example fenotiazina and Pimozidum; some antihistaminic drugs, for example terfenadin; lithium drugs, quinine, pentamidine and sparfloksatsin.

Electrolytic imbalance, in particular a hypopotassemia, considerably increases risk of lengthening of an interval of Q-Tc. Thus, it is necessary to avoid simultaneous use of the medicaments causing an electrolytic imbalance.

central nervous system Depressants. Thioridazine can strengthen the oppression of central nervous system caused by other depressants of central nervous system, such as drugs, alcohol, sedative and narcotic analgetics.

MAO Inhibitors. Simultaneous use can increase the sedation depth, a constipation, dryness in a mouth and hypotonia.

Lities. Serious complications, neurotoxic extrapyramidal side effects and episodes of sleepwalking were described at patients at simultaneous use of lithium and fenotiazin including thioridazine.

Anticholinergic medicines. Undesirable anticholinergic effects develop at simultaneous use of anticholinergic medicaments and thioridazine. Stringent control and dose adjustment at simultaneous use with such medicines as antihistaminic, tricyclic antidepressants and atropinsoderzhashchy connections are necessary.

Antiparkinsonichesky medicines. The efficiency of medicines can be reduced at their simultaneous use with thioridazine.

Adrenergic vasoconstrictors. Due to the ability to lower the arterial blood pressure fenotiazin can reduce angiotonic activity of adrenergic vasoconstrictors (for example ephedrine, Phenylephrinum).

Fenilpropanolamin. There is information on developing of ventricular arrhythmia at simultaneous use of a fenilpropanolamin and thioridazine.

Thiazide diuretics. Simultaneous use of a fenotiazin and thiazide diuretics can lead to heavy hypotension and diuretic - the induced hypopotassemia, it can exponentiate thioridazine - the induced cardiotoxicity.

Antacids, anti-diarrheal medicines. These medicaments can reduce gastrointestinal absorption of fenotiazin which are applied orally. Antacids should not be used for 2 h after reception of fenotiazin.

Anti-diabetic medicines. Fenotiazin influences carbohydrate metabolism and level of glucose in blood at patients with diabetes.

Overdose

overdose Symptoms, including symptoms of overdose of fenotiazin:

from a cardiovascular system: cardiac arrhythmia, arterial hypotension, shock, changes of the ECG, increase in an interval of Q-T and P-R, change of ST and T, bradycardia, sinus tachycardia, AV blockade, ventricular tachycardia, fibrillation of ventricles, disturbance of a rhythm as torsade de pointes, myocardial changes;

from nervous system: a mydriasis, a miosis, xeroderma, dryness in a mouth, hyperaemia of a mucous membrane of a nose, congestion of a nose, an urination delay, a disorder of vision, disturbance of the speech, drowsiness, disturbance of consciousness, orientation, visual acuity, excitement, motive hyperactivity, extrapyramidal symptoms, spasms, a coma, agitation, a hypothermia, a hyperthermia, insomnia, an areflexia;

from a respiratory system: respiratory depression, apnoea, fluid lungs;

from a GIT: reduction of a vermicular movement, constipation, Ilheus, paralytic impassability of intestines, nausea, vomiting;

from an urinary system: oliguria, uraemia. The toxic dose and concentration is definitely not estimated at blood of fenotiazin.

Treatment: to wash out a stomach, to accept activated carbon. To provide passability of airways, to carry out monitoring of a cardiovascular system and the ECG for detection of arrhythmia; to correct the level of electrolytes, acid-base balance, to apply lidocaine, Phenytoinum, Isoproterenolum, a defibrillation. It is necessary to avoid use of Disopyramidum, procaineamide, quinidine as they, as well as thioridazine, extend Q–Tc interval (see. Special INSTRUCTIONS and CONTRAINDICATIONS). It is necessary to be careful at lidocaine use as it increases risk of developing of spasms.

To treatment of arterial hypotension is applied in/in administration of solutions, vasoconstrictive medicines (apply Phenylephrinum to treatment of refractory hypotension, levarterenol or metaraminol and also epinephrine, a dopamine).

to decrease in absorption and acceleration of removal of drug.

should not cause vomiting, considering risk of appearance of dystonia and inhalation of emetic masses.

apply a difengidramin To treatment of acute extrapyramidal symptoms a hydrochloride or benztropine mezilat.

For treatment of spasms should avoid use of barbiturates as they strengthen the respiratory depression caused by action of fenotiazin.

as medicament contacts proteins of blood plasma.

Storage conditions

In the dry place at a temperature not above 25 °C.