(Levomepromazine)

Trade names

Tizercin.
Group affiliation

Antipsychotic drug

Description of the active substance (INN)

Levomepromazine
Dosage form

solution for intravenous and intramuscular administration, film-coated tablets
pharmachologic effect

Indications

Contraindications

Side effects

From the outside nervous system: extrapyramidal disorders with a predominance of akineto-hypotonic syndrome, drowsiness, dizziness, increased fatigue. From the cardiovascular system: decreased blood pressure, orthostatic hypotension, tachycardia. From the outside digestive system: dry mouth, nausea, constipation, liver dysfunction. From the hematopoietic system: inhibition of bone marrow hematopoiesis (agranulocytosis). Other: allergic reactions, dysmenorrhea, mastalgia, atropine-like effects (in newborns). Overdose. Symptoms: epileptic syndrome, coma. Treatment: resuscitation measures, symptomatic therapy in a specialized department of the hospital.
Dosage and administration

special instructions

Interaction

Catad_pgroup Anxiolytics (tranquilizers)

Tizercin solution - official* instructions for use

*registered by the Ministry of Health of the Russian Federation (according to grls.rosminzdrav.ru)

Registration number:

P N012432/01-20.09.2011

Tradename:

TIZERTSIN ®

International nonproprietary name:

levomepromazine

Dosage form:

solution for infusion and intramuscular administration

Compound:

active substance: levomepromazine 25 mg,
Excipients: anhydrous citric acid 9 mg, monothioglycerol 7.5 mg, sodium chloride 6 mg, water for injection up to 1 ml.

Description:

A colorless or slightly colored transparent solution with a characteristic odor.

Pharmacotherapeutic group:

antipsychotic (neuroleptic)

ATX code: N05A A02

Pharmacological properties

Pharmacodynamics:

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderately blocks H1-histamine and M-cholinergic receptors. Causes a decrease in blood pressure (BP).
The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems.
The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.
Extrapyramidal side effects of levomepromazine are less pronounced than those of “typical” antipsychotics. Levomepromazine increases pain threshold. Thanks to the ability to enhance the effects non-narcotic analgesics, this drug can be used for adjuvant therapy in acute and chronic pain syndrome.
The maximum analgesic effect develops within 20-40 minutes after intramuscular administration and lasts approximately 4 hours.

Pharmacokinetics:

After intramuscular administration, the maximum concentration in the blood plasma is reached after 30-90 minutes. Passes through histohematic barriers, including the blood-brain barrier, and is distributed in organs and tissues.
Levomepromazine is rapidly metabolized in the liver by demethylation to form conjugates with sulfuric or glucuronic acid, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylmonomethotrimeprazine) has pharmacological activity, the remaining metabolites are inactive. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours.

Indications for use:

Psychomotor agitation of various etiologies:

• for bipolar disorders
• for oligophrenia
• for epilepsy

as well as others mental disorders, occurring with:

• agitation
• anxiety
• panic
• phobias
• persistent insomnia

Strengthening the effect of analgesics, general anesthesia, H1-histamine receptor blockers.

Pain syndrome (trigeminal neuralgia, neuritis facial nerve, herpes zoster).

Contraindications:

• hypersensitivity to the components of the drug and phenothiazine derivatives,
• overdose of drugs that cause inhibition of the central nervous system (alcohol, general anesthesia, sleeping pills),
• angle-closure glaucoma,
• urinary retention,
• Parkinson's disease,
• multiple sclerosis,
• myasthenia gravis, hemiplegia,
• severe arterial hypotension, inhibition of bone marrow hematopoiesis (granulocytopenia),
• porphyria,
• lactation,
• childhood up to 12 years old.

CAREFULLY
Epilepsy, patients with a history of cardiovascular diseases, especially in old age (cardiac muscle conduction disorders, arrhythmias, congenital long QT syndrome). Pregnancy and lactation

Pregnancy and breastfeeding

The drug should not be used during pregnancy unless the risk to the fetus has been carefully weighed against the benefit to the mother. Levomepromazine passes into breast milk. In this regard, and in the absence of controlled studies, its use in breastfeeding contraindicated.
If it is necessary to take the drug during lactation, the issue of stopping breastfeeding should be decided.

Directions for use and dosage:

Parenteral administration is used when it is impossible to take the drug orally. The usual daily dose is 75-100 mg (for 2-3 injections) in bed rest under the control of blood pressure and pulse. If necessary daily dose increase to 200-250 mg.
When administered intramuscularly, the drug should be injected deep into the muscle.
Intravenous drip infusions are also used, for which the drug Tizercin ® should be dilute(50 - 100 mg of the drug in 250 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution) and administer slowly through an IV.
There is insufficient clinical experience with the parenteral use of levomepromazine in children under 12 years of age.
If there are strict indications for children over 12 years of age, doses ranging from 0.35 mg/kg/day to 3.0 mg/kg/day are recommended.

Side effect

From the cardiovascular system:
decreased blood pressure, orthostatic hypotension (with accompanying weakness, dizziness and loss of consciousness), Adams-Stokes syndrome, tachycardia, prolongation of the QT interval (arrhythmogenic effect, pirouette-type arrhythmia) (see section "Special instructions"). Cases of sudden death (possibly caused by cardiac causes) have been reported when taking phenothiazine antipsychotics.

From the circulatory system and lymphatic system:
pancytopenia, agranulocytosis, leukopenia, thrombocytopenia, eosinophilia.

From the central nervous system:
drowsiness, dizziness, increased fatigue, confusion, slurred speech, visual hallucinations, catatonia, disorientation, extrapyramidal symptoms with a predominance of akineto-hypotonic syndrome (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), epileptic seizures, increased intracranial pressure, malignant neuroleptic syndrome (NMS) (see also section “Special instructions”).

From the side of metabolism:
weight loss, galactorrhea, menstrual irregularities, mastalgia. Pituitary adenomas have been reported in some patients receiving phenothiazine derivatives, but establishing a causal relationship between the use of these drugs and tumor development is necessary. additional research.

From the reproductive and urinary system:
difficulty urinating, discoloration of urine, impaired contractions of the uterine muscles.

From the gastrointestinal tract:
vomiting, nausea, constipation, discomfort in the abdominal area, dry mouth, liver damage (jaundice, cholestasis).

From the skin:
exfoliative dermatitis, urticaria, erythema, photosensitivity, hyperpigmentation.

From the organs of vision:
pigmentary retinopathy, deposits in the lens and cornea.

Allergic reactions:
laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.

Other: hyperthermia (may be the first sign of NMS), pain and swelling at the injection sites.

Overdose

Symptoms: decreased blood pressure, hyperthermia, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the “pirouette” type, atrioventricular block), depression of consciousness varying degrees severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures, neuroleptic malignant syndrome.

Treatment: It is recommended to monitor the following indicators: acid-base balance, fluid and electrolyte balance, kidney function, urine volume, liver enzyme activity, ECG readings, and in patients with neuroleptic malignant syndrome - additionally serum CPK levels and body temperature. Symptomatic treatment should be carried out based on the results of the assessment of the above parameters. In case of decreased blood pressure, intravenous fluid replacement, Trendelenburg position, and the use of dopamine and/or norepinephrine are indicated. (Due to the pro-arrhythmogenic effect of levomepromazine, it is necessary to provide conditions for resuscitation, and when administering dopamine and/or norepinephrine, an ECG must be performed). In case of an overdose of antipsychotics, it is not recommended to use epinephrine (adrenaline).
The use of lidocaine (lignocaine) and, if possible, long-acting arrhythmic drugs should also be avoided.
To eliminate seizures, use diazepam or, for recurrent seizures, phenytoin or phenobarbitone. If rhabdomyolysis occurs, mannitol is prescribed.
There is no specific antidote.
Forced urination, hemodialysis and hemoperfusion are ineffective.
convulsions, dystonic reactions of the muscles of the head and neck can lead to the entry of vomit into Airways. Gastric lavage, along with monitoring vital signs, is indicated even 12 hours after taking the drug, since its natural emptying is slow due to the m-anticholinergic effect of levomepromazine. An additional reduction in drug absorption is achieved by using activated carbon and laxatives.

Interaction with other drugs

The simultaneous use of levomepromazine and the following drugs should be avoided:

• Antihypertensive drugs due to the risk of a pronounced decrease in blood pressure.
• Monoamine oxidase inhibitors (MAO), because it is possible to increase the duration of action of levomepromazine and increase the severity of its side effects.

Caution should be exercised when used simultaneously with the following drugs:

• Drugs with m-anticholinergic activity (tricyclic antidepressants; H1-histamine receptor blockers; some antiparkinsonian drugs; atropine, scopolamine, suxamethonium) enhance the m-anticholinergic effect of levmepromazine (paralytic intestinal obstruction, urinary retention, glaucoma). When used concomitantly with scopolamine, extrapyramidal side effects were observed.
• CNS depressants (narcotic analgesics, general anesthesia, anxiolytics, sedatives and sleeping pills, tranquilizers, tricyclic antidepressants), enhance the inhibitory effect of levomepromazine on the central nervous system.
• CNS stimulants (eg, amphetamine derivatives): levomepromazine reduces their psychostimulant effect.
• Levodopa: Levomepromazine reduces the effect of levodopa.
• Oral hypoglycemic agents: when used simultaneously with levomepromazine, their effectiveness decreases, which requires dose adjustment.
• Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and diuretics that lower blood potassium concentrations) increase the risk of QT prolongation and therefore increase the risk of arrhythmia.
• Drugs that cause photosensitivity, when used simultaneously with levomepromazine, increase the likelihood of photosensitivity.
• Alcohol increases central nervous system inhibition and increases the likelihood of extrapyramidal side effects when used simultaneously with levomepromazine.
• Antacids reduce absorption of gastrointestinal tract(levomepromazine should be prescribed 1 hour before or 4 hours after taking antacids).
• Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.
• Dilevalol, like levomepromazine, inhibits metabolism, which leads to a mutual enhancement of the effect of both drugs. If they are used simultaneously, it may be necessary to reduce the dosage of one or both drugs. A similar interaction with other beta-blockers is possible.
• Levomepromazine and its non-hydroxylated metabolites are potent inhibitors of cytochrome P450 2D6. Concomitant use of levomepromazine with medicines metabolized primarily by cytochrome P450 2D6 may result in increased concentrations of these drugs, which may increase the undesirable effects of these drugs.

special instructions

The use of the drug should be discontinued if allergic reactions.
Concomitant use with central nervous system depressants, MAO inhibitors and anticholinergic blockers requires special caution (see section "Interaction with other drugs").
The drug should be prescribed with extreme caution to patients with impaired liver and/or kidney function.
Elderly patients are predisposed to orthostatic hypotension, as well as the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, treatment of these patients should begin with low doses with their gradual increase.
In older people with dementia treated with antipsychotics, slight increase mortality risk. There is insufficient data to determine the exact magnitude of the risk, and the reason for this is unknown increased risk. Tizercin ® is not approved for use in the treatment of behavioral disorders associated with dementia.
To avoid the development of orthostatic hypotension, the patient should lie down for half an hour after the first dose. If dizziness occurs after administration of the drug, you should remain in bed after each dose until the dizziness disappears.
In cases of parenteral administration of the drug Tisercin®, the injection sites should, if necessary, be alternated, since the drug can cause local irritation and tissue damage.
It is also necessary to be careful when prescribing the drug to patients (especially the elderly) with a history of cardiovascular diseases, patients with congestive heart failure, conduction disorders, arrhythmia, and congenital long QT interval syndrome. Before starting treatment with Tizercin®, an ECG must be performed to exclude any cardiovascular disorder that may contraindicate the use of the drug.
There are reports of QT prolongation, arrhythmias and, very rarely, torsade de pointes (TdP) with phenothiazines (see section " Side effect»).
If hyperthermia occurs during antipsychotic therapy, the possibility of neuroleptic malignant syndrome (NMS) should be excluded. This potentially life-threatening syndrome is characterized by the following symptoms: muscle rigidity, hyperthermia, confusion, dysfunction of the autonomic nervous system (unstable arterial pressure, tachycardia, arrhythmia, increased sweating), catatonia, increased activity of creatine phosphokinase (CPK), myoglobinuria (rhabdomyolysis) and acute renal failure. If they occur, as well as if during treatment hyperthermia of unknown etiology occurs without other clinical symptoms ZNS, use of the drug Tizercin ® should be stopped immediately.
After sudden withdrawal of a drug used in high doses or for a long time, the following may occur: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety, as well as the development of tolerance to the sedative effect of phenothiazine derivatives and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually.
Many antipsychotics, including levomepromazine, can lower the seizure threshold and cause epileptiform seizures. ECG changes. For this reason, when titrating the dose of the drug Tizercin ®, all patients with epilepsy must ensure careful clinical observation and ECG monitoring.
The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the use of the drug. Therefore, during long-term treatment, regular monitoring of liver function is required.
Agranulocytosis and leukopenia have been reported in some patients receiving phenothiazines.
Despite the rarity of such cases, during long-term therapy with levomepromazine it is necessary to regularly monitor the leukocyte count.
During treatment and until the drug stops working (within 4-5 days after discontinuation of the drug), alcohol consumption is prohibited.
Before and during treatment, it is recommended to regularly monitor the following indicators: blood pressure, liver function (especially in patients with liver disease), leukocyte formula blood, ECG (for cardiovascular diseases and in elderly patients), potassium concentration in blood serum. Periodic monitoring of the level of electrolytes in the blood and its correction is necessary (especially when planning long-term therapy).

Impact on the ability to drive vehicles and operate machinery

At the beginning of treatment (for a period the duration of which depends on the patient’s response), driving a car and performing work associated with an increased risk of accidents is prohibited. Subsequently, the severity of the ban is determined individually for each patient.

Release form:

Solution for infusion and intramuscular administration 25 mg/ml.
1 ml in ampoules made of colorless hydrolytic glass type I, with red and blue code rings and with a break point.
5 ampoules per blister pack, sealed with PVC/PET/PE film.
2 blister packs in a cardboard box along with instructions for use.

Best before date:

2 years. Do not use the drug after the expiration date indicated on the package.

Storage conditions:

In a place protected from light at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Conditions for dispensing from pharmacies:

On prescription.

Manufacturer
JSC Pharmaceutical Plant EGIS,
1106 Budapest, st. Keresturi, 30-38 HUNGARY

Representative office of JSC "EGIS Pharmaceutical Plant" (Hungary), Moscow
121108, Moscow, st. Ivan Franko, d. 8.

Levomepromazine INN

International name: Levomepromazine

Dosage form: solution for intravenous and intramuscular administration, film-coated tablets

Chemical name:

(R) - 2 - methoxy - N, N, - trimethyl - 10H - phenothiazine - 10 - propanamine (as maleate (1:1) or hydrochloride)

Pharmachologic effect:

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has a sedative, hypnotic, hypotensive, analgesic, moderate antiemetic, hypothermic, muscle relaxant, moderate antihistamine and moderate anticholinergic effect. The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems. The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus. Reduces the productive symptoms of psychosis - delusions, hallucinations, psychomotor agitation.

Pharmacokinetics:

Quickly and completely absorbed by any route of administration. TCmax when taken orally - 1-3 hours, when administered intramuscularly - 0.5-1.5 hours. Passes through histohematic barriers, including the BBB, and is distributed in organs and tissues. Metabolized in the liver by demethylation to form the active metabolite N-desmethylomono-methotrimeprazine (further converted to monosulfoxide). T1/2 - 15-78 hours. Excreted (including metabolites) - by the kidneys and with bile.

Indications:

Psychomotor agitation (accompanied by fear, anxiety, anger), psychosis, paranoid-hallucinatory syndromes (schizophrenia, delirious psychosis), epilepsy, mental retardation, agitated depression (as an adjuvant), neuroses, insomnia, premedication (increasing the effect of analgesics, antihistamines and means for general anesthesia); pain syndrome (trigeminal neuralgia, neuritis of the facial nerve, herpes zoster, etc.), itchy dermatoses.

Contraindications:

Hypersensitivity, renal/liver failure, jaundice, inhibition of bone marrow hematopoiesis (granulocytopenia), arterial hypotension, decompensated CHF, pregnancy, lactation; angle-closure glaucoma; parkinsonism, acute infectious diseases viral, fungal or bacterial nature (incl. chicken pox, herpes zoster); coma caused by intoxication with ethanol, drugs and sleeping pills. With caution. Epilepsy.

Dosing regimen:

Orally, intramuscularly, intravenously in a stream, intravenously by drip (per 250 ml of 0.9% NaCl solution or 5% dextrose solution). For psychosis and severe agitation, start with parenteral administration of 25-75 mg, increasing, if necessary, to 200-250 mg with intramuscular administration and up to 75-100 mg with intravenous administration. Then patients are transferred to taking the drug orally, 50-100 mg/day (if necessary, up to 400 mg). For moderately severe psychopathy - orally, in 2-4 doses, starting from 25-50 mg, gradually increasing the dose to 200-300 mg/day, after achieving the effect, gradually reduce it to maintenance doses - 25-100 mg. To relieve acute alcoholic psychosis - 50-75 mg intravenously. According to indications - intramuscularly, 100-150 mg for 5-7 days. The maximum daily dose is 400 mg. To prevent the development of orthostatic collapse during treatment, bed rest is required. For neuroses - orally, 12.5-50 mg.

Side effects:

From the nervous system: extrapyramidal disorders with a predominance of akineto-hypotonic syndrome, drowsiness, dizziness, increased fatigue. From the cardiovascular system: decreased blood pressure, orthostatic hypotension, tachycardia. From the digestive system: dry mouth, nausea, constipation, impaired liver function. From the hematopoietic system: inhibition of bone marrow hematopoiesis (agranulocytosis). Other: allergic reactions, dysmenorrhea, mastalgia, atropine-like effects (in newborns). When taking phenothiazine antipsychotics, cases of sudden death (including those possibly caused by cardiac causes) have been reported; may prolong the QT interval - the risk of developing ventricular arrhythmias (especially against the background of initial bradycardia, hypokalemia, prolonged QT). Overdose. Symptoms: epileptic syndrome, coma. Treatment: resuscitation measures, symptomatic therapy in a specialized department of the hospital.

Special instructions:

Elderly patients can be prescribed only with systematic monitoring of blood pressure. When administered parenterally, it is recommended to change the injection site due to the possibility of a local tissue reaction to the injection. To prevent collapse within 30 minutes after injection, be sure to horizontal position. Systematic implementation is recommended general analysis blood and liver function tests; during the period of taking the drug, ethanol consumption is not permissible. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.

Interaction:

Incompatible with MAO inhibitors (increased central nervous system excitation), antihypertensive drugs (orthostatic hypotension). Strengthens the sedative and m-anticholinergic effects of benzodiazepines, hypnotics, analgesics, general anesthetics and tricyclic antidepressants. Reduces the effectiveness of levodopa. Antacid drugs reduce absorption in the gastrointestinal tract (levomepromazine should be prescribed 1 hour before or 4 hours after taking antacid drugs). Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.

Levomepromazine price and availability in city pharmacies

Attention! The above is a reference table and information may have changed. Data on prices and availability changes in real time, to view them - you can use the search (the search always contains up-to-date information), and also if you need to place an order for a medicine, select city areas to search, or search only for those that are currently open pharmacies.

The above list is updated at least once every 6 hours (it was updated on 04/24/2019 at 01:08 - Moscow time). Check the prices and availability of drugs through the search (the search bar is located at the top), as well as by calling pharmacies before visiting the pharmacy. The information contained on the site cannot be used as recommendations for self-medication. Before using medications, be sure to consult your doctor.

Formula: C19H24N2OS, chemical name: (R)-2-methoxy-N,N,beta-trimethyl-10H-phenothiazine-10-propanamine (as maleate (1:1) or hydrochloride).
Pharmacological group: neurotropic drugs/neuroleptics.
Pharmachologic effect: neuroleptic, analgesic, antipsychotic, antiemetic.

Pharmacological properties

Levomepromazine is a phenothiazine derivative. Levomepromazine has a blocking effect on dopamine receptors of various brain structures (including mesocortical, mesolimbic), thereby causing an antipsychotic effect. Blockade of dopamine receptors increases the secretion of prolactin by the pituitary gland. Levomepromazine reduces the productive symptoms (hallucinations, delusions, psychomotor agitation) of psychosis. Levomepromazine has a pronounced adrenergic blocking, moderate antihistamine and anticholinergic effect; has an analgesic, sedative and hypotensive effect. It has a moderate or weak extrapyramidal effect, which is less pronounced than that of "typical" antipsychotics. The antiemetic effect is associated with blockade or inhibition of dopamine D2 receptors in the chemoreceptor trigger zone of the cerebellum, as well as with blockade of the vagus nerve in the gastrointestinal tract. The antiemetic effect of levomepromazine is less pronounced than that of chlorpromazine. The sedative effect of levomepromazine is due to the blockade of adrenoreceptors of the reticular formation of the brain stem. Hypothermic action is possible due to the blockade of dopamine receptors in the hypothalamus. Levomepromazine does not increase depression and has some antidepressant activity, unlike chlorpromazine. Levomepromazine increases the pain threshold, therefore, enhances the effects of non-narcotic analgesics and can be used for auxiliary treatment in acute and chronic pain syndrome. The maximum analgesic effect develops within 20-40 minutes after intramuscular injection and lasts approximately 4 hours.
Levomepromazine is absorbed quite completely and quickly via any route of administration. The maximum concentration is reached after 0.5 - 1.5 hours with intramuscular injection and 1 - 3 hours after ingestion. Levomepromazine passes through histohematogenous barriers (including the blood-brain barrier) and is distributed in tissues and organs. Levomepromazine is intensively biotransformed. The main active metabolite of levomepromazine is N-desmethylmonomethotrimeprazine, which is formed by demethylation and then converted to monosulfoxide. The remaining metabolites are inactive. The half-life of levomepromazine is 16–78 hours. Levomepromazine is excreted in the bile and urine mainly as metabolites (conjugates with glucuronic or sulfuric acid), approximately 1% is excreted unchanged.

Indications

Psychomotor agitation of various origins (in chronic and acute schizophrenia, psychoses, including intoxication and senile, bipolar disorder, epilepsy, mental retardation); other mental disorders that occur with anxiety, agitation, panic, persistent insomnia, phobias; to enhance the effect of drugs for general anesthesia, analgesics, antihistamines; pain syndrome with neuritis of the facial nerve, trigeminal neuralgia, herpes zoster; itchy dermatoses.

Method of administration of levomepromazine and dose

Levomepromazine is taken orally, administered intramuscularly, intravenously. Relief of agitation begins with parenteral administration of 25 - 75 mg, if necessary - up to 75 - 100 mg intravenously or 200 - 250 mg intramuscularly. Gradually switch to oral administration at 50–100 mg per day (if necessary, up to 400 mg). In outpatient practice, 12.5–50.0 mg per day is prescribed orally.
Intramuscular injections are painful; Due to possible local tissue reactions, injection sites should be changed.
The combined use of levomepromazine with drugs that depress the central nervous system, m-anticholinergics, requires special caution.
The use of levomepromazine should be discontinued if allergic reactions occur.
Patients with impaired renal and/or liver function should prescribe the drug with extreme caution.
Elderly patients are predisposed to the sedative and m-anticholinergic effects of phenothiazines, as well as to orthostatic hypotension. They also often develop extrapyramidal adverse reactions. Therefore, therapy in elderly patients should be started with low doses and gradually increased.
Older people with dementia who took antipsychotic drugs had a small increase in the risk of mortality. There is insufficient data to accurately determine the magnitude of the risk, and the reason for this increased risk is also unknown. Levomepromazine should not be used to treat behavioral disorders that are associated with dementia.
A systematic assessment of the functional state of the liver and a general blood test is recommended; in weakened and elderly patients it is necessary to control blood pressure. After using levomepromazine (especially for the first time and the first few days), regardless of its route of administration and dose, the patient should lie down for 0.5 - 1 hour to prevent orthostatic collapse. If dizziness persists after using levomepromazine, bed rest should be observed after each use of the drug until the dizziness disappears. With rapid increases in doses, especially in patients with vascular insufficiency or in elderly patients, drug-induced delirium may develop.
Caution is required when prescribing levomepromazine to patients (especially the elderly) who have a history of cardiovascular pathology, patients with conduction disorders, congestive heart failure, arrhythmia, and congenital long QT interval syndrome. Before starting therapy, it is necessary to perform electrocardiography to exclude any cardiovascular diseases that may serve as a contraindication to the use of the drug. There is information about the occurrence of arrhythmia, prolongation of the QT interval, and pirouette-type arrhythmia during treatment with phenothiazines.
If hyperthermia develops during treatment with levomepromazine, it is necessary to exclude neuroleptic malignant syndrome, which poses a potential threat to life and is characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, catatonia, dysfunction of the autonomic nervous system (increased sweating, tachycardia, unstable blood pressure, arrhythmia) , myoglobinuria (rhabdomyolysis), increased activity of creatine phosphokinase, acute renal failure. If they develop, as well as if hyperthermia of unknown origin appears during therapy without other clinical symptoms of neuroleptic malignant syndrome, the use of levomepromazine should be stopped immediately.
If levomepromazine is suddenly discontinued, especially when used long-term or in high doses, headache, nausea, tremor, vomiting, increased sweating, insomnia, tachycardia, anxiety, cross-tolerance to various antipsychotic drugs and the development of tolerance to the sedative effects of phenothiazines may occur. Therefore, withdrawal of levomepromazine should always be done gradually.
Levomepromazine, like many antipsychotics, can lower the seizure threshold and cause epileptiform changes in the electroencephalogram. In this regard, when selecting a dose in patients with epilepsy, constant monitoring of clinical parameters and electroencephalogram is necessary.
The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the use of levomepromazine. Therefore, during long-term therapy it is necessary to regularly monitor the functional state of the liver.
During therapy and for 4 - 5 days after its completion, it is imperative to refuse alcoholic drinks.
During long-term treatment with levomepromazine, regular monitoring of the leukocyte count is necessary, since agranulocytosis and leukopenia have been observed in some patients receiving phenothiazines.
Before and during therapy, regular monitoring of blood pressure, liver function (especially in patients with liver pathology), leukocyte count, electrocardiography (especially in elderly patients and patients with cardiovascular diseases), potassium levels in the blood plasma is recommended . It is also necessary to periodically monitor the level of electrolytes in the blood and adjust it (especially when planning long-term treatment).
During treatment with levomepromazine, it is necessary to refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions (including driving a car and other vehicles).

Contraindications for use

Hypersensitivity (including hypersensitivity to other phenothiazine derivatives), angle-closure glaucoma, combined use of antihypertensive drugs, monoamine oxidase inhibitors; Parkinson's disease, urinary retention, multiple sclerosis, hemiplegia, myasthenia gravis, porphyria, chronic heart failure in the stage of decompensation, severe arterial hypotension, severe renal and/or liver failure, liver disease, suppression of bone marrow hematopoiesis, diseases of the hematopoietic organs, breastfeeding, pregnancy, children under 12 years of age, overdose of drugs that cause inhibition of the central nervous system (general anesthetics, alcohol, sleeping pills and others).

Restrictions on use

Epilepsy, patients with a history of cardiovascular diseases (arrhythmia, cardiac muscle conduction disorders, congenital long QT syndrome and others), pathological changes blood pictures, liver dysfunction, Reye's syndrome, breast cancer, predisposition to the development of glaucoma, chronic diseases respiratory organs, epileptic seizures, peptic ulcer stomach and duodenum, exhausted and weakened patients, old age.

Use during pregnancy and breastfeeding

Levomepromazine should not be used during pregnancy unless the expected benefit to the mother is greater possible risk for the fetus. The use of levomepromazine is contraindicated during breastfeeding, as the drug is excreted in breast milk. During therapy with levomepromazine, breastfeeding should be stopped.

Side effects of levomepromazine

Cardiovascular system and blood (hemostasis, hematopoiesis): decreased blood pressure, tachycardia, orthostatic hypotension (with accompanying dizziness, weakness, loss of consciousness), arrhythmogenic effect, QT interval prolongation, torsade de pointes tachycardia, Morgagni-Adams-Stokes syndrome, cases of sudden death (possibly caused by cardiac causes), agranulocytosis , pancytopenia, eosinophilia, leukopenia, thrombocytopenia.
Nervous system and sensory organs: drowsiness, increased fatigue, dizziness, slurred speech, confusion, extrapyramidal symptoms with a predominance of akinetic-hypotonic syndrome (dyskinesia, opisthotonus, parkinsonism, dystonia, hyperreflexia), disorientation, increased intracranial pressure, epileptic seizures, hallucinations, catatonia, neuroleptic malignant syndrome , akathisia, parkinsonian syndrome, tardive dyskinesia, thermoregulation disorders, pigmentary retinopathy, deposits in the lens and cornea, blurred vision.
Genitourinary system: impaired urination, difficulty urinating, discoloration of urine, impaired contractions of the uterine muscles, menstrual irregularities, gynecomastia, galactorrhea, mastalgia.
Digestive system: constipation, dry mouth, nausea, abdominal discomfort, vomiting, dyspeptic symptoms, cholestatic jaundice, jaundice, liver damage, cholestasis.
Allergic reactions: peripheral edema, laryngeal edema, anaphylactoid reactions, urticaria, bronchospasm, erythema multiforme, exfoliative dermatitis.
Others: weight loss, weight gain, hyperpigmentation, increased photosensitivity, pigmentation, erythema, photosensitivity, hyperthermia (may be the first sign of neuroleptic malignant syndrome), pain and swelling at the injection site, pituitary adenoma.

Interaction of levomepromazine with other substances

Levomepromazine is incompatible with antihypertensive drugs (due to the risk of developing orthostatic hypotension) and monoamine oxidase inhibitors (due to decreased inactivation of the drug in the liver, the risk of developing extrapyramidal disorders is increased); the combined use of these drugs is contraindicated.
Due to increased anticholinergic effects (urinary retention, paralytic ileus, glaucoma and others), caution is required when using levomepromazine together with anticholinergic drugs (including histamine H1 receptor blockers, tricyclic antidepressants, some antiparkinsonian drugs, scopolamine, atropine, succinylcholine). When levomepromazine was used concomitantly with scopolamine, extrapyramidal adverse reactions were observed.
Drugs that depress the central nervous system (general anesthesia, narcotic analgesics, non-narcotic analgesics, anxiolytics, hypnotics and sedatives, tricyclic antidepressants, benzodiazepines) enhance the inhibitory effect of levomepromazine on the central nervous system.
Levomepromazine reduces the effect of drugs that stimulate the central nervous system (for example, amphetamine derivatives).
Levomepromazine reduces the effectiveness of oral antidiabetic agents (requires dose adjustment) and the antiparkinsonian activity of levodopa.
Drugs that prolong the QT interval (macrolides, antiarrhythmic drugs, antifungal azoles, antidepressants, cisapride, antihistamines, potassium-lowering diuretics), when used together with levomepromazine, increase the risk of prolonging the QT interval and increase the risk of developing arrhythmias.
Antacids that contain magnesium, calcium or aluminum reduce the absorption of levomepromazine in the gastrointestinal tract (levomepromazine must be taken 1 hour before or 4 hours after the use of antacids).
Levomepromazine, when combined with alcohol, increases the inhibition of the central nervous system and increases the risk of developing extrapyramidal side reactions.
The combined use of 4-nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl] benzamide hydrochloride (Refralon®) with levomepromazine is contraindicated due to the risk of developing polymorphic ventricular tachycardia of the “pirouette” type.
Caution is required when co-administering rilmenidine with levomepromazine.
Due to the risk of developing polymorphic ventricular tachycardia of the "pirouette" type and other ventricular arrhythmias, the combined use of amisulpride with levomepromazine is not recommended.
Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression when used together with levomepromazine.
Drugs that cause photosensitivity, when used together with levomepromazine, increase the risk of developing photosensitivity.
Dilevalol, like levomepromazine, inhibits metabolism, which, when used together, leads to a mutually enhanced effect. If they are used together, it may be necessary to reduce the dosage of one or both drugs. The same interaction of levomepromazine with other beta-blockers is not excluded.
Levomepromazine and its metabolites are potent inhibitors of cytochrome P450 2D6. The simultaneous use of levomepromazine with drugs that are metabolized mainly with the participation of cytochrome P450 2D6 may lead to an increase in the concentration of these drugs, as a result of which their undesirable effects may appear or intensify.

Overdose

In case of an overdose of levomepromazine, conduction disturbances in the myocardium develop (prolongation of the QT interval, atrioventricular block, ventricular tachycardia of the “pirouette” type), arterial hypotension, sedation, extrapyramidal symptoms, depression of consciousness of varying severity (including coma), hyperthermia, epileptic seizures , neuroleptic malignant syndrome.
Treatment: gastric lavage (indicated even 12 hours after taking levomepromazine orally, since natural excretion is slow due to the m-anticholinergic effect of the drug), using activated charcoal and laxatives (to further reduce the absorption of levomepromazine); It is not recommended to induce vomiting, since dystonic reactions of the head and neck muscles, epileptic convulsions can lead to aspiration of vomit into the respiratory tract; control of vital functions (including electrolyte and fluid balance, acid-base balance, liver enzyme activity, kidney function, urine volume, electrocardiography readings, in patients with neuroleptic malignant syndrome - additionally body temperature and serum creatinine phosphokinase level); symptomatic treatment(carried out based on the results of assessing the above indicators): when blood pressure decreases, the Trendelenburg position, intravenous fluid replacement, administration of norepinephrine and/or dopamine are indicated (due to the pro-arrhythmogenic effect of levomepromazine, it is necessary to provide conditions for resuscitation, and when administering norepinephrine or dopamine, conduct electrocardiography); with the development of rhabdomyolysis, mannitol is prescribed; for seizures, use diazepam or, for recurrent seizures, phenobarbitone or phenytoin. In case of an overdose of antipsychotics, it is not recommended to use adrenaline (epinephrine). The use of lidocaine (lignocaine) and long-acting arrhythmic drugs should also be avoided. Forced diuresis, hemoperfusion, hemodialysis are not effective. A specific antidote is unknown.

NEUROLEPTICS

Tizercin

Latin name of the drug:

Tizercin Tisercin®

Tradename drug:

Tizercin

Active ingredient INN:

Levomepromazine*

Dosage form:

Film-coated tablets

Compound:

Active substance: 25 mg levomepromazine, excipients: magnesium stearate, sodium starch glycolate, povidone, microcrystalline cellulose, potato starch, lactose, titanium dioxide, hypromellose, dimethicone, magnesium stearate

Description:

Round, slightly biconvex, film-coated tablets, white, odorless

Pharmacodynamics:

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderate antihistamine and M-anticholinergic effects. Causes a decrease in blood pressure (BP).

The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems. The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.

Extrapyramidal side effects in levomepromazine are less pronounced than in "classical" antipsychotics. Levomepromazine increases the pain threshold. Due to the ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy in acute and chronic pain syndrome.

Pharmacokinetics:

The maximum concentration of the drug in the blood plasma is reached 1-3 hours after ingestion. Passes through histohematic barriers, including the blood-brain barrier, and is distributed in organs and tissues.

Levomepromazine is rapidly metabolized in the liver by demethylation to sulfate and glucuronide conjugates, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylomono-methotrimeprazine) has pharmacological activity, the remaining metabolites are inactive. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours.

Indications:

Psychomotor agitation of various etiologies:

• for schizophrenia (acute and chronic)
• for bipolar disorders
• for senile, intoxication and other psychoses
• for oligophrenia
• for epilepsy

as well as other mental disorders occurring with:

• agitation
• anxiety
• panic
• phobias
• persistent insomnia

Strengthening the action of analgesics, general anesthesia, antihistamines. Pain syndrome (trigeminal neuralgia, neuritis of the facial nerve, herpes zoster).

Contraindications:

• simultaneous use of antihypertensive drugs,
• hypersensitivity to phenothiazines,
• overdose of drugs that cause CNS inhibition (alcohol, general anesthetics, sleeping pills),
• angle-closure glaucoma,
• urinary retention,
• Parkinson's disease,
• multiple sclerosis,
• myasthenia gravis, hemiplegia,
• chronic heart failure in the stage of decompensation,
• severe renal/liver failure,
• severe arterial hypotension,
• inhibition of bone marrow hematopoiesis (granulocytopenia),
• porphyria,
• lactation,
• children up to 12 years of age.

Carefully: epilepsy, patients with a history of cardiovascular diseases, especially in old age (cardiac muscle conduction disorders, arrhythmias, congenital long QT interval syndrome).

Pregnancy and lactation:

Pregnancy
The drug should not be used during pregnancy unless the risk to the fetus has been carefully weighed against the benefit to the mother.

Lactation
Levomepromazine passes into breast milk. In this regard, and in the absence of controlled studies, its use during breastfeeding is contraindicated. If it is necessary to take the drug during lactation, the issue of stopping breastfeeding should be decided.

Directions for use and dosage:

Orally, starting with a daily dose of 25-50 mg in several doses (the maximum part of the daily dose should be administered before bedtime), increasing it daily by 25-50 mg until the patient’s condition improves. In patients resistant to other antipsychotics, the daily dose can be increased more quickly by adding 50-75 mg per day. Average daily doses are 200-300 mg.

After the patient’s condition improves, the dose should be reduced to a maintenance dose, the amount of which is determined individually.

In outpatient practice, patients with neurotic disorders are prescribed a daily dose of 12.5-50 mg (1/2-2 tablets).

For patients with psychosis, with severe psychomotor agitation, it is advisable to begin therapy with levomepromazine with parenteral administration

To prevent the development of orthostatic collapse during treatment, bed rest is required. .

Side effect:

Cardiovascular system: the most common side effect is decreased blood pressure and orthostatic hypotension. Tachycardia, Morgagni-Adams-Stokes syndrome, prolongation of the QT interval (arrhythmogenic effect, tachycardia of the "pirouette" type) are also possible (see also section "Contraindications").

Hematopoietic system: pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.

Central nervous system: confusion, slurred speech, extrapyramidal symptoms with a predominance of akineto-hypotonic syndrome, epileptic seizures, increased intracranial pressure, neuroleptic malignant syndrome (NMS).

Endocrine system and metabolism: galactorrhea, menstrual irregularities, weight loss. The development of pituitary adenoma has been described in some patients receiving long-term phenothiazines, but further research is needed to establish a causal relationship with these drugs.

Genitourinary system: discoloration of urine, urination disorders.

Gastrointestinal tract: dry mouth, abdominal discomfort, nausea, vomiting, constipation, liver damage (jaundice, cholestasis).

Skin reactions: photosensitivity, erythema, pigmentation.

Vision: with long-term use, deposits in the lens and cornea, pigmentary retinopathy.

Allergic reactions: laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.

Others: hyperthermia (may be the first sign of NMS), pain and swelling at injection sites.

Overdose:

Symptoms: Arterial hypotension, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the "pirouette" type, atrioventricular block), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures.

Treatment: resuscitation measures, symptomatic therapy. A specific antidote is not known. Forced diuresis, hemodialysis and hemoperfusion are not effective.

Interaction with other drugs:

The simultaneous use of the following drugs should be avoided:

• Antihypertensive due to the risk of a pronounced decrease in blood pressure.
• Monoamine oxidase inhibitors MAO, because it is possible to increase the duration of the effect of the drug Tizercin and the severity of its side effects.

Caution should be exercised when combined with the following:

Anticholinergic drugs (tricyclic antidepressants; H1-histamine blockers; some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma). When combined with scopolamine, extrapyramidal side effects were observed.

CNS depressants (narcotic analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the inhibitory effect of the drug on the central nervous system.

CNS stimulants (for example, amphetamine derivatives) - decreased psychostimulant effect.

Levodopa: The effect of this drug is weakened.

Oral antidiabetic drugs: Their effectiveness is reduced, requiring dose adjustment.

Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and potassium-lowering diuretics) increase the risk of QT prolongation and therefore increase the risk of arrhythmia.

Drugs that cause photosensitivity: this effect may be enhanced. Alcohol: increases central nervous system inhibition and increases the likelihood of extrapyramidal side effects.

Antacids: reduce absorption in the gastrointestinal tract (levomepromazine should be prescribed 1 hour before or 4 hours after taking antacids).

Special instructions:

The use of the drug should be discontinued if an allergic reaction occurs.

During pregnancy, the drug should be prescribed after carefully weighing the risks and benefits (see section "Pregnancy and lactation").

Concomitant use with CNS depressants, MAO inhibitors and anticholinergics requires special caution (see Interactions section).

Particular caution is needed when prescribing drugs to patients with renal and/or liver failure due to the risk of drug accumulation.

Elderly patients are predisposed to orthostatic hypotension and the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, low initial doses and their gradual increase are especially important in this category of patients.

To avoid the development of orthostatic hypotension, the patient should lie down for half an hour after the first dose. If dizziness occurs after administration of the drug, you should remain in bed after each dose.

If hyperthermia occurs during antipsychotic therapy, neuroleptic malignant syndrome (NMS) should be excluded. NZS - deadly dangerous disease, characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), increased concentrations of creatine phosphokinase (CPK), myoglobinuria (rhabdomyolysis) and acute renal failure.

If they occur, as well as if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, the administration of Tizercin® should be stopped immediately.

After sudden withdrawal of a drug used in high doses or for a long time, the following may occur: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety, as well as the development of tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics.

For this reason, drug withdrawal should always be done gradually.

Many antipsychotics, including levomepromazine, can lower the seizure threshold and cause epileptiform EEG changes. Therefore, when selecting the dose of Tizercin in patients with epilepsy, clinical parameters and EEG should be constantly monitored.

The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function is required.

The consumption of alcoholic beverages should be prohibited during treatment and until the effects of the drug disappear (within 4-5 days after stopping the administration of Tizercin®.

• arterial pressure,
• liver function (especially in patients with liver disease),
• blood formula,
• ECG (for cardiovascular diseases and elderly patients).

Driving cars and working with machinery:

During the treatment period, you should refrain from driving a car and performing work associated with an increased risk of accidents.

Release form:

50 tablets in a brown glass bottle with a PE cap. 1 bottle along with instructions for use in a cardboard box.

Shelf life:

5 years. The shelf life is indicated on the box. Do not use after the expiry date stated on the packaging.

Storage conditions:

The drug belongs to the list No. 1 of potent substances of the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation.

Store at a temperature of 15-25° C, out of the reach of children.

Conditions for dispensing from pharmacies:

Manufacturer:

Pharmaceutical plant EGIS A.O.
1106 Budapest, st. Keresturi, 30-38 Hungary
Tel: (36-1) 265-5555 Fax: (36-1) 265-5529

Representative office of JSC "EGIS Pharmaceutical Plant" (Hungary):
Moscow, st. Ivana Franko, 8

The drug belongs to the list No. 1 of potent substances of the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation.
The drug in the form of film-coated tablets should be stored out of the reach of children at a temperature of 15° to 25°C.

Expiration date from date of manufacture

Product description

White film-coated tablets, round, slightly biconvex, odorless.

pharmachologic effect

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderate antihistamine and m-anticholinergic effects. Causes a decrease in blood pressure.
The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical systems.
The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.
Extrapyramidal side effects of levomepromazine are less pronounced than those of “classical” antipsychotics. Levomepromazine increases the pain threshold. Due to its ability to enhance the effects of analgesics, general anesthesia and antihistamines, this drug can be used for adjuvant therapy for acute and chronic pain syndrome.

Pharmacokinetics

Suction
After oral administration, Cmax in blood plasma is achieved within 1-3 hours.
After intramuscular administration, Cmax in blood plasma is reached within 30-90 minutes.
Distribution
Penetrates through histohematic barriers, including the BBB, and is distributed in organs and tissues.
Metabolism
Levomepromazine is rapidly metabolized in the liver by demethylation to form sulfate and glucuronide conjugates, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylomono-methotrimeprazine) has pharmacological activity, the remaining metabolites are inactive.
breeding
T1/2 is 15-30 hours.

Indications for use

Psychomotor agitation of various etiologies: in schizophrenia (acute and chronic), in bipolar disorders, in psychoses (including senile and intoxication), in oligophrenia, in epilepsy;
- other mental disorders occurring with agitation, anxiety, panic, phobias, persistent insomnia;
- enhancing the effect of analgesics, general anesthesia, histamine H1 receptor blockers;
- pain syndrome (trigeminal neuralgia, facial neuritis, herpes zoster).

Use during pregnancy and lactation

The drug should not be used during pregnancy, unless the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

special instructions

The use of the drug should be discontinued if allergic reactions occur.
Concomitant use with CNS depressants, MAO inhibitors and m-anticholinergics requires special caution.
The drug should be prescribed with extreme caution to patients with impaired liver and/or kidney function.
Elderly patients are predisposed to orthostatic hypotension, as well as the m-anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, treatment of these patients should be started with low doses and gradually increased.
In older people with dementia who were treated with antipsychotics, there was a small increase in the risk of mortality. There are insufficient data to determine the exact magnitude of the risk, and the reason for this increased risk is unknown. Do not use Tizercin® for the treatment of behavioral disorders associated with dementia. To avoid the development of orthostatic hypotension, the patient should lie down for half an hour after the first dose. If dizziness occurs after administration of the drug, you should remain in bed after each dose until the dizziness disappears.
In cases of parenteral administration of the drug Tisercin®, the injection sites should, if necessary, be alternated, since the drug can cause local irritation and tissue damage.
It is also necessary to be careful when prescribing the drug to patients (especially the elderly) with a history of cardiovascular diseases, patients with congestive heart failure, conduction disorders, arrhythmia, and congenital long QT interval syndrome. Before starting treatment with Tizercin®, an ECG must be performed to exclude any cardiovascular disorder that may contraindicate the use of the drug.
There are reports of prolongation of the QT interval, the occurrence of arrhythmias and, very rarely, torsades de pointes arrhythmias with phenothiazines.
If hyperthermia occurs during antipsychotic therapy, the possibility of NMS should be excluded. This potentially life-threatening syndrome is characterized by the following symptoms: muscle rigidity, hyperthermia, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), catatonia, increased CPK activity, myoglobinuria (rhabdomyolysis), and acute renal failure. If they occur, and if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, the use of the drug Tizercin® should be stopped immediately.
After sudden withdrawal of a drug used in high doses or for a long time, the following may occur: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety, as well as the development of tolerance to the sedative effect of phenothiazine derivatives and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually.
Many antipsychotics, incl. Levomepromazine may lower the seizure threshold and cause epileptiform EEG changes. For this reason, when titrating the dose of the drug Tizercin® in all patients with epilepsy, it is necessary to ensure careful clinical observation and monitoring of the EEG.
The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the use of the drug. Therefore, during long-term treatment, regular monitoring of liver function is required.
Agranulocytosis and leukopenia have been reported in some patients receiving phenothiazines. Despite the rarity of such cases, during long-term therapy with levomepromazine it is necessary to regularly monitor the leukocyte count. During treatment and until the drug stops working (within 4-5 days after discontinuation of the drug), alcohol consumption is prohibited.
Before and during treatment, it is recommended to regularly monitor the following indicators: blood pressure, liver function (especially in patients with liver diseases), leukocyte blood count, ECG (for cardiovascular diseases and in elderly patients), serum potassium concentration. Periodic monitoring of the level of electrolytes in the blood and its correction is necessary (especially when planning long-term therapy).

At the beginning of treatment (for a period the duration of which depends on the patient’s response), driving a car and performing work associated with an increased risk of accidents is prohibited. Subsequently, the severity of the ban is determined individually for each patient.

With caution (Precautions)

With extreme caution, the drug should be prescribed to patients with hepatic insufficiency due to the risk of cumulation of the drug.
The drug is contraindicated in severe liver failure.
With extreme caution, the drug should be prescribed to patients with renal insufficiency due to the risk of cumulation of the drug.
The drug is contraindicated in severe renal failure.
Contraindication: children under 12 years of age.
Use with caution in patients with a history of cardiovascular disease, especially in the elderly (conduction disorders of the heart muscle).

Contraindications

Concomitant use of antihypertensive drugs;
- an overdose of drugs that have a depressant effect on the central nervous system (alcohol, general anesthetics, sleeping pills);
- angle-closure glaucoma;
- urinary retention;
- Parkinson's disease;
- multiple sclerosis;
- myasthenia;
- hemiplegia;
- chronic heart failure in the stage of decompensation;
- severe renal failure;
- severe liver failure;
- severe arterial hypotension;
- inhibition of bone marrow hematopoiesis (granulocytopenia);
- porphyria;
- lactation;
- children under 12 years of age;
- hypersensitivity to levomepromazine and other phenothiazines.
Use with caution in epilepsy, in patients with a history of cardiovascular disease, especially in old age (disorders in the conduction of the heart muscle, arrhythmias, congenital prolongation of the QT interval).

Dosage and administration

Inside is prescribed, starting with a dose of 25-50 mg / day in divided doses (the maximum part of the daily dose should be given at bedtime), increasing it daily by 25-50 mg until the patient's condition improves. In patients resistant to other neuroleptics, the daily dose can be increased more rapidly, increasing it by 50-75 mg / day. Average daily doses are 200-300 mg.
After the patient's condition improves, the dose should be reduced to a maintenance dose, the value of which is determined individually.
In outpatient practice, patients with neurotic disorders are prescribed the drug in a daily dose of 12.5-50 mg (1/2-2 tab.).
The drug is administered parenterally when it is not possible to take it orally. The daily dose is 75-100 mg, divided into 2-3 injections, under bed rest under the control of blood pressure and pulse. If necessary, the daily dose is increased to 200-250 mg.
Injected intramuscularly (deeply) or intravenously.
For administration as an intravenous drip infusion, Tizercin® (50-100 mg) should be diluted in 250 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution and administered slowly through a dropper.
Clinical experience with the parenteral use of the drug in children under the age of 12 years is not enough. In the presence of strict indications for children over 12 years of age, doses of 0.35-3 mg / kg body weight / day are recommended.

Overdose

Symptoms: decrease in blood pressure, hyperthermia, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the "pirouette" type, AV blockade), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures, NMS .
Treatment: it is recommended to monitor acid-base balance, fluid and electrolyte balance, kidney function, urine volume, liver enzyme activity, ECG readings, and in patients with NMS, additional serum CPK levels and body temperature. Symptomatic treatment should be carried out based on the results of the assessment of the above parameters. In the case of a decrease in blood pressure, intravenous fluid administration, the Trendelenburg position, the use of dopamine and / or norepinephrine are indicated. In view of the proarrhythmic effect of levomepromazine, it is necessary to provide conditions for resuscitation, and with the introduction of dopamine and / or noradrenaline, an ECG should be performed. In case of an overdose of antipsychotics, the use of adrenaline is not recommended. The use of lidocaine and, if possible, long-acting arrhythmic drugs should also be avoided. To eliminate seizures, use diazepam or, with recurrence of convulsive attacks, phenytoin. If rhabdomyolysis occurs, mannitol is prescribed. There is no specific antidote. Forced urination, hemodialysis and hemoperfusion are ineffective.
It is not recommended to induce vomiting, since intermittent epileptic convulsions, dystonic reactions of the muscles of the head and neck can lead to the entry of vomit into the respiratory tract. Gastric lavage, along with the control of vital signs, is indicated even 12 hours after taking the drug, since its natural excretion is slow due to the m-anticholinergic action of levomepromazine. An additional reduction in drug absorption is achieved by using activated carbon and laxatives.

Side effect

From the outside of cardio-vascular system: decreased blood pressure, orthostatic hypotension (with accompanying weakness, dizziness and loss of consciousness), Adams-Stokes syndrome, tachycardia, prolongation of the QT interval (arrhythmogenic effect, pirouette-type arrhythmia). Cases of sudden death (possibly caused by cardiac causes) have been reported when taking phenothiazine antipsychotics.
From the hematopoietic system: pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.
From the central nervous system: drowsiness, dizziness, increased fatigue, confusion, slurred speech, visual hallucinations, catatonia, disorientation, extrapyramidal symptoms with a predominance of akinetic-hypotonic syndrome (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), epileptic seizures, increased intracranial pressure, ZNS.
Metabolism: weight loss, galactorrhea, menstrual irregularities, mastalgia. Pituitary adenomas have been reported in some patients receiving phenothiazine derivatives, but further research is needed to establish a causal relationship between the use of these drugs and tumor development.
From the reproductive and urinary system: difficulty urinating, discoloration of urine, impaired contractions of the uterine muscles.
From the digestive system: dry mouth, discomfort in the abdomen, nausea, vomiting, constipation, liver damage (jaundice, cholestasis).
From the skin: photosensitivity, erythema, hyperpigmentation.
From the organ of vision: deposits in the lens and cornea, pigmentary retinopathy.
Allergic reactions: laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.
Other: hyperthermia (may be the first sign of NMS), pain and swelling at the injection sites.

Compound

1 tab.

Interaction with other drugs

Concomitant use of levomepromazine and the following drugs should be avoided:
- antihypertensive drugs due to the risk of a pronounced decrease in blood pressure;
- MAO inhibitors, tk. it is possible to increase the duration of action of levomepromazine and increase the severity of its side effects.
Caution should be exercised when used concomitantly with the following drugs
Drugs with m-anticholinergic activity (tricyclic antidepressants; histamine H1 receptor blockers; some antiparkinsonian drugs; atropine, scopolamine, suxamethonium) enhance the m-anticholinergic effect of levmepromazine (paralytic intestinal obstruction, urinary retention, glaucoma). When used concomitantly with scopolamine, extrapyramidal side effects were observed.
CNS depressants (opioid analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the inhibitory effect of levomepromazine on the central nervous system.
CNS stimulants (eg, amphetamine derivatives): levomepromazine reduces their psychostimulant effect.
Levodopa: Levomepromazine reduces the effect of levodopa.
Oral hypoglycemic agents: when used simultaneously with levomepromazine, their effectiveness decreases, which requires dose adjustment.
Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and potassium-lowering diuretics) increase the risk of QT prolongation and therefore increase risk of arrhythmia.
Drugs that cause photosensitivity, when used simultaneously with levomepromazine, increase the likelihood of photosensitivity.
Ethanol enhances central nervous system inhibition and increases the likelihood of extrapyramidal side effects when used simultaneously with levomepromazine.
Antacids reduce absorption in the gastrointestinal tract (levomepromazine should be prescribed 1 hour before or 4 hours after taking antacids).
Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.
Dilevalol, like levomepromazine, inhibits metabolism, which leads to a mutual enhancement of the effect of both drugs. If they are used simultaneously, it may be necessary to reduce the dosage of one or both drugs. A similar interaction with other beta-blockers is possible.
Levomepromazine and its non-hydroxylated metabolites are potent inhibitors of CYP2D6. Concomitant use of levomepromazine with drugs primarily metabolized by CYP2D6 may result in increased concentrations of these drugs, which may increase the adverse effects of these drugs.

Release form

White film-coated tablets, round, slightly biconvex, odorless.
1 tab.
levomepromazine hydromaleate 33.8 mg,
which corresponds to the content of levomepromazine 25 mg
Excipients: magnesium stearate - 1 mg, sodium starch glycolate - 2 mg, povidone - 8 mg, microcrystalline cellulose - 10 mg, potato starch - 15.2 mg, lactose - 40 mg.
Shell composition: titanium dioxide - 0.758 mg, hypromellose - 2.632 mg, dimethicone - 0.355 mg, magnesium stearate - 0.255 mg.
50 pcs. - brown glass bottles with a PE cap, with first opening control and an accordion shock absorber (1) - cardboard packs.

Release form, composition and packaging

Film-coated tablets white, round, slightly biconvex, odorless.

Excipients: sodium starch glycolate, potato starch, lactose, magnesium stearate, povidone, microcrystalline cellulose.

Shell composition: hypromellose, dimethicone, magnesium stearate, titanium dioxide.

50 pcs. - dark glass bottles (1) - packs of cardboard.

Solution for infusions and intramuscular injections colorless or pale green, transparent, odorless.

Excipients: sodium disulfite, ascorbic acid, water d/i.

1 ml - colorless glass ampoules (5) - contour cell packaging (2) - cardboard packs.

Clinical and pharmacological group

Antipsychotic drug (neuroleptic)

pharmachologic effect

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderate antihistamine and m-anticholinergic effects. Causes a decrease in blood pressure.

The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical systems.

The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D 2 receptors of the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.

Extrapyramidal side effects in levomepromazine are less pronounced than in "classical" antipsychotics. Levomepromazine increases the pain threshold. Due to its ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy for acute and chronic pain syndrome.

The maximum analgesic effect develops within 20-40 minutes after intramuscular administration and lasts approximately 4 hours.

Pharmacokinetics

Suction

After oral administration, Cmax in blood plasma is reached after 1-3 hours.

After i / m administration, C max in blood plasma is reached in 30-90 minutes.

Distribution

Penetrates through histohematic barriers, including the BBB, and is distributed in organs and tissues.

Metabolism

Levomepromazine is rapidly metabolized in the liver by demethylation to sulfate and glucuronide conjugates, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylomono-methotrimeprazine) has pharmacological activity, the remaining metabolites are inactive.

breeding

T 1/2 is 15-30 hours.

A small part of the administered dose (1%) is excreted unchanged in urine and feces.

Indications for use of the drug

- psychomotor agitation of various etiologies: with schizophrenia (acute and chronic), with bipolar disorders, with psychoses (including senile and intoxication), with oligophrenia, with epilepsy;

- other mental disorders occurring with agitation, anxiety, panic, phobias, persistent insomnia;

- enhancing the effect of analgesics, general anesthesia, antihistamines;

- pain syndrome (trigeminal neuralgia, facial neuritis, herpes zoster).

Dosage regimen

Inside prescribed starting with a dose of 25-50 mg/day in several doses (the maximum part of the daily dose should be prescribed before bedtime), increasing it daily by 25-50 mg until the patient’s condition improves. In patients resistant to other neuroleptics, the daily dose can be increased more rapidly, increasing it by 50-75 mg / day. Average daily doses are 200-300 mg.

After the patient’s condition improves, the dose should be reduced to a maintenance dose, the amount of which is determined individually.

IN outpatient practice for patients with neurotic disorders the drug is prescribed in a daily dose of 12.5-50 mg (1/2-2 tab.).

Parenterally the drug is administered in the absence of the possibility of its intake. The daily dose is 75-100 mg, divided into 2-3 injections, under bed rest under the control of blood pressure and pulse. If necessary, the daily dose is increased to 200-250 mg.

Injected intramuscularly (deeply) or intravenously.

For administration as an intravenous drip infusion, Tizercin ® (50-100 mg) should be diluted in 250 ml of saline or isotonic glucose solution (dextrose) and administered slowly through a dropper.

Patients with psychosis, with severe psychomotor agitation it is advisable to start therapy with levomepromazine with parenteral administration.

To prevent the development of orthostatic collapse during treatment, bed rest is required.

Side effect

From the cardiovascular system: most often - a decrease in blood pressure, orthostatic hypotension; possible - tachycardia, Morgagni-Adams-Stokes syndrome, prolongation of the QT interval (arrhythmogenic effect, tachycardia of the "pirouette" type). Cases of sudden death (possibly caused by cardiac causes) have been reported when taking phenothiazine antipsychotics.

From the hematopoietic system: pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.

From the side of the central nervous system: drowsiness, dizziness, increased fatigue, confusion, slurred speech, extrapyramidal symptoms with a predominance of akinetic-hypotonic syndrome, epileptic seizures, increased intracranial pressure, neuroleptic malignant syndrome (NMS).

From the endocrine system: galactorrhea, menstrual disorders, mastalgia, weight loss. With long-term use, cases of the development of pituitary adenoma have been described, however, additional research is needed to establish the causal relationship of its development with phenothiazine derivatives.

From the urinary system: discoloration of urine, urination disorders.

From the digestive system: dry mouth, abdominal discomfort, nausea, vomiting, constipation, liver damage (jaundice, cholestasis).

Dermatological reactions: photosensitivity, erythema, pigmentation.

From the side of the organ of vision: with long-term use, deposits in the lens and cornea and pigmentary retinopathy are possible.

Allergic reactions: laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.

Others: hyperthermia (may be the first sign of NMS), pain and swelling at the injection sites.

Contraindications to the use of the drug

- concomitant use of antihypertensive drugs;

- overdose of drugs that have a depressant effect on the central nervous system (alcohol, general anesthetics, sleeping pills);

- angle-closure glaucoma;

- urinary retention;

- Parkinson's disease;

- multiple sclerosis;

- myasthenia;

- hemiplegia;

- chronic heart failure in the stage of decompensation;

- severe renal failure;

- severe liver failure;

- severe arterial hypotension;

- inhibition of bone marrow hematopoiesis (granulocytopenia);

- porphyria;

- lactation;

- children under 12 years of age;

- hypersensitivity to levomepromazine and other phenothiazines.

WITH caution used for epilepsy, in patients with a history of cardiovascular diseases, especially in old age (cardiac muscle conduction disorders, arrhythmias, congenital long QT interval syndrome).

Use of the drug during pregnancy and lactation

The drug should not be used during pregnancy, unless the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Adequate and strictly controlled clinical studies on the safety of Tizercin during lactation have not been conducted. Levomepromazine is excreted in breast milk. Given these facts, the use of the drug during breastfeeding is contraindicated. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Use for liver dysfunction

With extreme caution, the drug should be prescribed to patients with hepatic insufficiency due to the risk of cumulation of the drug.

The drug is contraindicated in severe liver failure.

Use for renal impairment

With extreme caution, the drug should be prescribed to patients with renal insufficiency due to the risk of cumulation of the drug.

The drug is contraindicated in severe renal failure.

special instructions

The use of the drug should be discontinued if allergic reactions develop.

Particular caution is required when used concomitantly with CNS depressants, MAO inhibitors and drugs with anticholinergic activity.

The drug should be prescribed with extreme caution to patients with renal and/or liver failure due to the risk of drug accumulation.

Elderly patients are predisposed to orthostatic hypotension, as well as to the development of anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, in this category of patients, it is especially important to use the drug in low initial doses and gradually increase them.

To avoid the development of orthostatic hypotension after the first dose, the patient should lie down for 30 minutes. If dizziness occurs after administration of the drug, you should remain in bed after each dose.

When administered parenterally, injection sites should be changed whenever possible, since the drug may have a local irritant effect and damage tissue.

If hyperthermia occurs during antipsychotic therapy, the development of NMS must be excluded. NMS is a deadly disease characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), increased concentrations of CPK, myoglobinuria (rhabdomyolysis) and acute renal failure. If these symptoms occur, as well as if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, the administration of Tizercin should be stopped immediately.

After sudden discontinuation of a drug used in high doses or for a long time, nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety may occur, as well as the development of tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually.

Many antipsychotics, incl. Levomepromazine may lower the seizure threshold and cause epileptiform EEG changes. Therefore, when selecting the dose of Tizercin ® in patients with epilepsy, clinical parameters and EEG should be constantly monitored.

The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function is required.

During the treatment period, avoid drinking alcohol until the effects of the drug disappear (within 4-5 days after stopping the use of Tizercin).

Control of laboratory parameters

Before and during treatment, it is recommended to regularly monitor blood pressure, liver function indicators (especially in patients with liver disease), perform peripheral blood tests, and ECG (for cardiovascular diseases and elderly patients).

Impact on the ability to drive vehicles and operate machinery

During the treatment period, you should refrain from driving a car and performing work associated with an increased risk of accidents.

Overdose

Symptoms: arterial hypotension, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the "pirouette" type, AV block), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures.

Treatment: resuscitation measures, symptomatic therapy. A specific antidote is not known. Forced diuresis, hemodialysis and hemoperfusion are not effective.

Drug interactions

The simultaneous use of Tizercin with antihypertensive drugs should be avoided due to the risk of a pronounced decrease in blood pressure; with MAO inhibitors, tk. it is possible to increase the duration of the effect of Tizercin and the severity of its side effects.

Tizercin ® should be used with caution in combination with drugs that have anticholinergic activity (tricyclic antidepressants; histamine H1 receptor blockers, some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma ), when combined with scopolamine, extrapyramidal side effects were observed; with drugs that depress the central nervous system (opioid analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tricyclic antidepressants), because the inhibitory effect of Tizercin on the central nervous system is enhanced; with drugs that have a stimulating effect on the central nervous system (including amphetamine derivatives), because there is a decrease in the psychostimulating effect; with levodopa, because there is a weakening of the effect of levodopa; with oral hypoglycemic agents, because their effectiveness decreases and dose adjustment is required; with drugs that prolong the QT interval (some antiarrhythmics, macrolide antibiotics, azole derivative antifungals, cisapride, some antidepressants, some antihistamines, as well as diuretics that reduce potassium levels), because the risk of prolongation of the QT interval and, consequently, the development of arrhythmia increases; with drugs that cause photosensitivity, due to the risk of its intensification; with ethanol, because the depressant effect on the central nervous system increases and the likelihood of developing extrapyramidal side effects increases.

Tizercin ® should be administered orally 1 hour before or 4 hours after taking antacids, because when used simultaneously, antacids reduce the absorption of levomepromazine from the gastrointestinal tract.

When used simultaneously with Tizercin, drugs that inhibit bone marrow hematopoiesis, the risk of developing myelosuppression increases.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug belongs to the list No. 1 of potent substances of the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation.

The drug in the form of film-coated tablets should be stored out of the reach of children, at a temperature of 15° to 25°C. Shelf life - 5 years.

The drug in the form of an injection solution should be stored out of the reach of children, protected from light, at a temperature of 15° to 25°C. Shelf life - 2 years.

Dispensing the drug

On prescription

Manufacturer's country of origin

Basic shelf life (in months)

Method of drug administration

Oral

Nosological classification ICD-10 (name)

Shingles with other complications of the nervous system; Schizophrenia; Schizotypal disorder; Chronic delusional disorders; Acute and transient mental disorders; Schizoaffective disorders; Non-organic psychosis, unspecified; Bipolar affective disorder; Phobic anxiety disorders (including agoraphobia, social phobias) ;Panic disorder [episodic paroxysmal anxiety];Mixed anxiety and depressive disorder;Unspecified mental retardation;Epilepsy;Trigeminal neuralgia;Facial nerve lesions

• Manufacturer
• Country of origin
• Product group
• Description
• Release forms
• Description of the dosage form
• pharmachologic effect
• Pharmacokinetics
• Special conditions
• Compound
• Tizercin indications for use
• Contraindications
• Dosage
• Side effects
• Drug interactions
• Overdose
• Storage conditions

Egis JSC pharmaceutical plant Egis Pharmaceutical plant JSC Egis Pharmaceutical plant JSC

Country of origin

Product group

Nervous system

Antipsychotic drug (neuroleptic)

Release forms

• 1 ml - colorless glass ampoules (5) - contour cell packaging (2) - cardboard packs. 50 - dark glass bottles (1) - cardboard packs.

Description of the dosage form

• The solution for infusion and intramuscular administration is colorless or pale green, transparent, odorless. Film-coated tablets

pharmachologic effect

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderate antihistamine and m-anticholinergic effects. Causes a decrease in blood pressure. The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical systems. The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus. Extrapyramidal side effects of levomepromazine are less pronounced than those of “classical” antipsychotics. Levomepromazine increases the pain threshold. Due to its ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy for acute and chronic pain syndrome. The maximum analgesic effect develops within 20-40 minutes after intramuscular administration and lasts approximately 4 hours.

Pharmacokinetics

Absorption After oral administration, Cmax in blood plasma is achieved within 1-3 hours. After intramuscular administration, Cmax in blood plasma is achieved within 30-90 minutes. Distribution Penetrates through histohematic barriers, including the blood-brain barrier, and is distributed in organs and tissues. Metabolism Levomepromazine is rapidly metabolized in the liver by demethylation to form sulfate and glucuronide conjugates, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylomono-methotrimeprazine) has pharmacological activity, the remaining metabolites are inactive. Elimination T1/2 is 15-30 hours. A small part of the administered dose (1%) is excreted unchanged in urine and feces.

Special conditions

The use of the drug should be discontinued if allergic reactions develop. Particular caution is required when used concomitantly with CNS depressants, MAO inhibitors and drugs with anticholinergic activity. The drug should be prescribed with extreme caution to patients with renal and/or liver failure due to the risk of drug accumulation. Elderly patients are predisposed to orthostatic hypotension, as well as to the development of anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, in this category of patients, it is especially important to use the drug in low initial doses and gradually increase them. To avoid the development of orthostatic hypotension after the first dose, the patient should lie down for 30 minutes. If dizziness occurs after administration of the drug, you should remain in bed after each dose. When administered parenterally, injection sites should be changed whenever possible, since the drug may have a local irritant effect and damage tissue. If hyperthermia occurs during antipsychotic therapy, the development of NMS must be excluded. NMS is a deadly disease characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), increased concentrations of CPK, myoglobinuria (rhabdomyolysis) and acute renal failure. If these symptoms occur, as well as if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, the administration of Tizercin should be stopped immediately. After sudden discontinuation of a drug used in high doses or for a long time, nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety may occur, as well as the development of tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually. Many antipsychotics, incl. Levomepromazine may lower the seizure threshold and cause epileptiform EEG changes. Therefore, when selecting the dose of Tizercin® in patients with epilepsy, clinical parameters and EEG should be constantly monitored. The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function is required. During long-term therapy, regular monitoring of peripheral blood patterns is recommended. During the treatment period, avoid drinking alcohol until the effects of the drug disappear (within 4-5 days after stopping the use of Tizercin).

• 1 ml Levomepromazine 25 mg Excipients: sodium disulfite, ascorbic acid, water for injection. Levomepromazine hydromaleate 33.8 mg, which corresponds to the content of levomepromazine 25 mg Excipients: sodium starch glycolate, potato starch, lactose, magnesium stearate, povidone, microcrystalline cellulose. Shell composition: hypromellose, dimethicone, magnesium stearate, titanium dioxide.

Tizercin indications for use

• - psychomotor agitation of various etiologies: with schizophrenia (acute and chronic), with bipolar disorders, with psychoses (including senile and intoxicating), with oligophrenia, with epilepsy; - other mental disorders occurring with agitation, anxiety, panic, phobias, persistent insomnia; - enhancing the effect of analgesics, general anesthesia, antihistamines; - pain syndrome (trigeminal neuralgia, facial neuritis, herpes zoster).

Tizercin contraindications

• - simultaneous use of antihypertensive drugs; - an overdose of drugs that have a depressant effect on the central nervous system (alcohol, general anesthetics, sleeping pills); - angle-closure glaucoma; - urinary retention; - Parkinson's disease; - multiple sclerosis; - myasthenia; - hemiplegia; - chronic heart failure in the stage of decompensation; - severe renal failure; - severe liver failure; - severe arterial hypotension; - inhibition of bone marrow hematopoiesis (granulocytopenia); - porphyria; - lactation; - children under 12 years of age; - hypersensitivity to levomepromazine and other phenothiazines. Use with caution in epilepsy, in patients with a history of cardiovascular disease, especially in old age (disorders in the conduction of the heart muscle, arrhythmias, congenital prolongation of the QT interval).

Tizercin dosage

• 25 mg 25 mg/ml 25 mg 25 mg/ml

Tizercin side effects

• From the cardiovascular system: most often - decreased blood pressure, orthostatic hypotension; possible - tachycardia, Morgagni-Adams-Stokes syndrome, prolongation of the QT interval (arrhythmogenic effect, tachycardia of the “pirouette” type). Cases of sudden death (possibly caused by cardiac causes) have been reported when taking phenothiazine antipsychotics. From the hematopoietic system: pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia. From the central nervous system: drowsiness, dizziness, increased fatigue, confusion, slurred speech, extrapyramidal symptoms with a predominance of akineto-hypotonic syndrome, epileptic seizures, increased intracranial pressure, neuroleptic malignant syndrome (NMS). From the endocrine system: galactorrhea, menstrual irregularities, mastalgia, weight loss. With long-term use, cases of the development of pituitary adenoma have been described, however, additional research is needed to establish the causal relationship of its development with phenothiazine derivatives. From the urinary system: discoloration of urine, urination disorders. From the digestive system: dry mouth, discomfort in the abdomen, nausea, vomiting, constipation, liver damage (jaundice, cholestasis). Dermatological reactions: photosensitivity, erythema, pigmentation. On the part of the organ of vision: with long-term use, deposits in the lens and cornea and pigmentary retinopathy are possible.

Drug interactions

The simultaneous use of Tizercin with antihypertensive drugs should be avoided due to the risk of a pronounced decrease in blood pressure; with MAO inhibitors, tk. it is possible to increase the duration of the effect of Tizercin and the severity of its side effects. Tizercin® should be used with caution in combination with drugs that have anticholinergic activity (tricyclic antidepressants; histamine H1 receptor blockers, some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma) , when combined with scopolamine, extrapyramidal side effects were observed; with drugs that depress the central nervous system (opioid analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tricyclic antidepressants), because the inhibitory effect of Tizercin on the central nervous system is enhanced; with agents that have a stimulating effect on the central nervous system. Symptoms: arterial hypotension, conduction disturbances in the heart muscle, depression of consciousness of varying severity, extrapyramidal symptoms, sedation, epileptic seizures. Treatment: resuscitation measures, symptomatic therapy.

Storage conditions

• keep away from children
• store in a place protected from light

Information provided by the State Register of Medicines.

Description of the active substance Levomepromazine/Levomepromazinum.

Formula: C19H24N2OS, chemical name: (R)-2-methoxy-N,N,beta-trimethyl-10H-phenothiazine-10-propanamine (as maleate (1:1) or hydrochloride).
Pharmacological group: neurotropic drugs/neuroleptics.
Pharmacological action: neuroleptic, analgesic, antipsychotic, antiemetic.

Pharmacological properties

Levomepromazine is a phenothiazine derivative. Levomepromazine has a blocking effect on dopamine receptors of various brain structures (including mesocortical, mesolimbic), thereby causing an antipsychotic effect. Blockade of dopamine receptors increases the secretion of prolactin by the pituitary gland. Levomepromazine reduces the productive symptoms (hallucinations, delusions, psychomotor agitation) of psychosis. Levomepromazine has a pronounced adrenergic blocking, moderate antihistamine and anticholinergic effect; has an analgesic, sedative and hypotensive effect. It has a moderate or weak extrapyramidal effect, which is less pronounced than that of "typical" antipsychotics. The antiemetic effect is associated with blockade or inhibition of dopamine D2 receptors in the chemoreceptor trigger zone of the cerebellum, as well as with blockade of the vagus nerve in the gastrointestinal tract. The antiemetic effect of levomepromazine is less pronounced than that of chlorpromazine. The sedative effect of levomepromazine is due to the blockade of adrenoreceptors of the reticular formation of the brain stem. Hypothermic action is possible due to the blockade of dopamine receptors in the hypothalamus. Levomepromazine does not increase depression and has some antidepressant activity, unlike chlorpromazine. Levomepromazine increases the pain threshold, therefore, enhances the effects of non-narcotic analgesics and can be used for auxiliary treatment in acute and chronic pain syndrome. The maximum analgesic effect develops within 20-40 minutes after intramuscular injection and lasts approximately 4 hours.
Levomepromazine is absorbed quite completely and quickly via any route of administration. The maximum concentration is reached after 0.5 - 1.5 hours with intramuscular injection and 1 - 3 hours after ingestion. Levomepromazine passes through histohematogenous barriers (including the blood-brain barrier) and is distributed in tissues and organs. Levomepromazine is intensively biotransformed. The main active metabolite of levomepromazine is N-desmethylmonomethotrimeprazine, which is formed by demethylation and then converted to monosulfoxide. The remaining metabolites are inactive. The half-life of levomepromazine is 16–78 hours. Levomepromazine is excreted in the bile and urine mainly as metabolites (conjugates with glucuronic or sulfuric acid), approximately 1% is excreted unchanged.

Indications

Psychomotor agitation of various origins (in chronic and acute schizophrenia, psychoses, including intoxication and senile, bipolar disorder, epilepsy, mental retardation); other mental disorders that occur with anxiety, agitation, panic, persistent insomnia, phobias; to enhance the effect of drugs for general anesthesia, analgesics, antihistamines; pain syndrome with neuritis of the facial nerve, trigeminal neuralgia, herpes zoster; itchy dermatoses.

Method of administration of levomepromazine and dose

Levomepromazine is taken orally, administered intramuscularly, intravenously. Relief of agitation begins with parenteral administration of 25 - 75 mg, if necessary - up to 75 - 100 mg intravenously or 200 - 250 mg intramuscularly. Gradually switch to oral administration at 50–100 mg per day (if necessary, up to 400 mg). In outpatient practice, 12.5–50.0 mg per day is prescribed orally.
Intramuscular injections are painful; Due to possible local tissue reactions, injection sites should be changed.
The combined use of levomepromazine with drugs that depress the central nervous system, m-anticholinergics, requires special caution.
The use of levomepromazine should be discontinued if allergic reactions occur.
Patients with impaired renal and/or liver function should prescribe the drug with extreme caution.
Elderly patients are predisposed to the sedative and m-anticholinergic effects of phenothiazines, as well as to orthostatic hypotension. They also often develop extrapyramidal adverse reactions. Therefore, therapy in elderly patients should be started with low doses and gradually increased.
Older people with dementia who took antipsychotic drugs had a small increase in the risk of mortality. There is insufficient data to accurately determine the magnitude of the risk, and the reason for this increased risk is also unknown. Levomepromazine should not be used to treat behavioral disorders that are associated with dementia.
A systematic assessment of the functional state of the liver and a general blood test is recommended; in weakened and elderly patients it is necessary to control blood pressure. After using levomepromazine (especially for the first time and the first few days), regardless of its route of administration and dose, the patient should lie down for 0.5 - 1 hour to prevent orthostatic collapse. If dizziness persists after using levomepromazine, bed rest should be observed after each use of the drug until the dizziness disappears. With rapid increases in doses, especially in patients with vascular insufficiency or in elderly patients, drug-induced delirium may develop.
Caution is required when prescribing levomepromazine to patients (especially the elderly) who have a history of cardiovascular pathology, patients with conduction disorders, congestive heart failure, arrhythmia, and congenital long QT interval syndrome. Before starting therapy, it is necessary to perform electrocardiography to exclude any cardiovascular diseases that may serve as a contraindication to the use of the drug. There is information about the occurrence of arrhythmia, prolongation of the QT interval, and pirouette-type arrhythmia during treatment with phenothiazines.
If hyperthermia develops during treatment with levomepromazine, it is necessary to exclude neuroleptic malignant syndrome, which poses a potential threat to life and is characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, catatonia, dysfunction of the autonomic nervous system (increased sweating, tachycardia, unstable blood pressure, arrhythmia) , myoglobinuria (rhabdomyolysis), increased activity of creatine phosphokinase, acute renal failure. If they develop, as well as if hyperthermia of unknown origin appears during therapy without other clinical symptoms of neuroleptic malignant syndrome, the use of levomepromazine should be stopped immediately.
If levomepromazine is suddenly discontinued, especially when used long-term or in high doses, headache, nausea, tremor, vomiting, increased sweating, insomnia, tachycardia, anxiety, cross-tolerance to various antipsychotic drugs and the development of tolerance to the sedative effects of phenothiazines may occur. Therefore, withdrawal of levomepromazine should always be done gradually.
Levomepromazine, like many antipsychotics, can lower the seizure threshold and cause epileptiform changes in the electroencephalogram. In this regard, when selecting a dose in patients with epilepsy, constant monitoring of clinical parameters and electroencephalogram is necessary.
The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the use of levomepromazine. Therefore, during long-term therapy it is necessary to regularly monitor the functional state of the liver.
During therapy and for 4 to 5 days after its completion, it is imperative to abstain from alcoholic beverages.
During long-term treatment with levomepromazine, regular monitoring of the leukocyte count is necessary, since agranulocytosis and leukopenia have been observed in some patients receiving phenothiazines.
Before and during therapy, regular monitoring of blood pressure, liver function (especially in patients with liver pathology), leukocyte count, electrocardiography (especially in elderly patients and patients with cardiovascular diseases), potassium levels in the blood plasma is recommended . It is also necessary to periodically monitor the level of electrolytes in the blood and adjust it (especially when planning long-term treatment).
During treatment with levomepromazine, it is necessary to refrain from engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions (including driving a car and other vehicles).

Contraindications for use

Hypersensitivity (including hypersensitivity to other phenothiazine derivatives), angle-closure glaucoma, combined use of antihypertensive drugs, monoamine oxidase inhibitors; Parkinson's disease, urinary retention, multiple sclerosis, hemiplegia, myasthenia gravis, porphyria, chronic heart failure in the stage of decompensation, severe arterial hypotension, severe renal and/or liver failure, liver disease, suppression of bone marrow hematopoiesis, diseases of the hematopoietic organs, breastfeeding, pregnancy, children under 12 years of age, overdose of drugs that cause inhibition of the central nervous system (general anesthetics, alcohol, sleeping pills and others).

Restrictions on use

Epilepsy, patients with a history of cardiovascular diseases (arrhythmia, conduction disorders of the heart muscle, congenital long QT syndrome and others), pathological changes in the blood picture, liver dysfunction, Reye's syndrome, breast cancer, predisposition to the development of glaucoma, chronic diseases respiratory organs, epileptic seizures, peptic ulcer of the stomach and duodenum, exhausted and weakened patients, old age.

Use during pregnancy and breastfeeding

Levomepromazine should not be used during pregnancy unless the expected benefit to the mother outweighs the possible risk to the fetus. The use of levomepromazine is contraindicated during breastfeeding, as the drug is excreted in breast milk. During therapy with levomepromazine, breastfeeding should be stopped.

Side effects of levomepromazine

Cardiovascular system and blood (hemostasis, hematopoiesis): decreased blood pressure, tachycardia, orthostatic hypotension (with accompanying dizziness, weakness, loss of consciousness), arrhythmogenic effect, prolongation of the QT interval, tachycardia of the “pirouette” type, Morgagni-Adams-Stokes syndrome , cases of sudden death (possibly caused by cardiac causes), agranulocytosis, pancytopenia, eosinophilia, leukopenia, thrombocytopenia.
Nervous system and sensory organs: drowsiness, increased fatigue, dizziness, slurred speech, confusion, extrapyramidal symptoms with a predominance of akinetic-hypotonic syndrome (dyskinesia, opisthotonus, parkinsonism, dystonia, hyperreflexia), disorientation, increased intracranial pressure, epileptic seizures, hallucinations , catatonia, neuroleptic malignant syndrome, akathisia, parkinsonian syndrome, tardive dyskinesia, thermoregulation disorders, pigmentary retinopathy, deposits in the lens and cornea, blurred vision.
Genitourinary system: impaired urination, difficulty urinating, discoloration of urine, impaired contraction of the uterine muscles, menstrual irregularities, gynecomastia, galactorrhea, mastalgia.
Digestive system: constipation, dry mouth, nausea, abdominal discomfort, vomiting, dyspeptic symptoms, cholestatic jaundice, jaundice, liver damage, cholestasis.
Allergic reactions: peripheral edema, laryngeal edema, anaphylactoid reactions, urticaria, bronchospasm, erythema multiforme, exfoliative dermatitis.
Other: weight loss, weight gain, hyperpigmentation, increased photosensitivity, pigmentation, erythema, photosensitivity, hyperthermia (may be the first sign of neuroleptic malignant syndrome), pain and swelling at the injection site, pituitary adenoma.

Interaction of levomepromazine with other substances

Levomepromazine is incompatible with antihypertensive drugs (due to the risk of developing orthostatic hypotension) and monoamine oxidase inhibitors (due to decreased inactivation of the drug in the liver, the risk of developing extrapyramidal disorders is increased); the combined use of these drugs is contraindicated.
Due to increased anticholinergic effects (urinary retention, paralytic ileus, glaucoma and others), caution is required when using levomepromazine together with anticholinergic drugs (including histamine H1 receptor blockers, tricyclic antidepressants, some antiparkinsonian drugs, scopolamine, atropine, succinylcholine). When levomepromazine was used concomitantly with scopolamine, extrapyramidal adverse reactions were observed.
Drugs that depress the central nervous system (general anesthesia, narcotic analgesics, non-narcotic analgesics, anxiolytics, hypnotics and sedatives, tricyclic antidepressants, benzodiazepines) enhance the inhibitory effect of levomepromazine on the central nervous system.
Levomepromazine reduces the effect of drugs that stimulate the central nervous system (for example, amphetamine derivatives).
Levomepromazine reduces the effectiveness of oral antidiabetic agents (requires dose adjustment) and the antiparkinsonian activity of levodopa.
Drugs that prolong the QT interval (macrolides, antiarrhythmic drugs, antifungal azoles, antidepressants, cisapride, antihistamines, potassium-lowering diuretics), when used together with levomepromazine, increase the risk of prolonging the QT interval and increase the risk of developing arrhythmias.
Antacids that contain magnesium, calcium or aluminum reduce the absorption of levomepromazine in the gastrointestinal tract (levomepromazine must be taken 1 hour before or 4 hours after the use of antacids).
Levomepromazine, when combined with alcohol, increases the inhibition of the central nervous system and increases the risk of developing extrapyramidal side reactions.
The combined use of 4-nitro-N-benzamide hydrochloride (Refralon®) with levomepromazine is contraindicated due to the risk of developing polymorphic ventricular tachycardia of the “pirouette” type.
Caution is required when co-administering rilmenidine with levomepromazine.
Due to the risk of developing polymorphic ventricular tachycardia of the "pirouette" type and other ventricular arrhythmias, the combined use of amisulpride with levomepromazine is not recommended.
Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression when used together with levomepromazine.
Drugs that cause photosensitivity, when used together with levomepromazine, increase the risk of developing photosensitivity.
Dilevalol, like levomepromazine, inhibits metabolism, which, when used together, leads to a mutually enhanced effect. If they are used together, it may be necessary to reduce the dosage of one or both drugs. The same interaction of levomepromazine with other beta-blockers is not excluded.
Levomepromazine and its metabolites are potent inhibitors of cytochrome P450 2D6. The simultaneous use of levomepromazine with drugs that are metabolized mainly with the participation of cytochrome P450 2D6 may lead to an increase in the concentration of these drugs, as a result of which their undesirable effects may appear or intensify.

Overdose

In case of an overdose of levomepromazine, conduction disturbances in the myocardium develop (prolongation of the QT interval, atrioventricular block, ventricular tachycardia of the “pirouette” type), arterial hypotension, sedation, extrapyramidal symptoms, depression of consciousness of varying severity (including coma), hyperthermia, epileptic seizures , neuroleptic malignant syndrome.
Treatment: gastric lavage (indicated even 12 hours after taking levomepromazine orally, since natural excretion is slow due to the m-anticholinergic effect of the drug), using activated charcoal and laxatives (to further reduce the absorption of levomepromazine); It is not recommended to induce vomiting, since dystonic reactions of the head and neck muscles, epileptic convulsions can lead to aspiration of vomit into the respiratory tract; control of vital functions (including electrolyte and fluid balance, acid-base balance, liver enzyme activity, kidney function, urine volume, electrocardiography readings, in patients with neuroleptic malignant syndrome - additionally body temperature and serum creatinine phosphokinase level); symptomatic treatment (carried out based on the results of assessing the above indicators): when blood pressure decreases, the Trendelenburg position, intravenous fluid replacement, administration of norepinephrine and/or dopamine are indicated (due to the pro-arrhythmogenic effect of levomepromazine, it is necessary to provide conditions for resuscitation, and when administering norepinephrine or dopamine – conducting electrocardiography); with the development of rhabdomyolysis, mannitol is prescribed; for seizures, use diazepam or, for recurrent seizures, phenobarbitone or phenytoin. In case of an overdose of antipsychotics, it is not recommended to use adrenaline (epinephrine). The use of lidocaine (lignocaine) and long-acting arrhythmic drugs should also be avoided. Forced diuresis, hemoperfusion, hemodialysis are not effective. A specific antidote is unknown.

Trade names of drugs with the active substance levomepromazine

Tizercin®

Tisercin is a fast-acting antipsychotic, effective against psychomotor agitation, acute psychoses of various etiologies, and depressive-paranoid schizophrenia. The manufacturer of Tisercin is EGIS JSC, Budapest, Hungary.

Basic properties

The active ingredient in Tizercin tablets is levomepromazine. The medicine belongs to the group of phenothiazine antipsychotic drugs, whose pharmacological properties are similar to Aminazine.

Levomepromazine blocks dopamine receptors in the brain and adrenergic receptors in the reticular formation. Due to this ability, Tizercin has the following effects:

Levomepromazine, in addition to a pronounced sedative effect that is superior to other antipsychotics, has hypnotic effect. The sleep that occurs after taking the medicine is close to physiological. Due to its ability to reduce agitation, the antipsychotic exhibits antidepressant activity.

Due to its ability to block H1-histamine receptors, the medicine is prescribed as an antihistamine.

The antipsychotic reaches therapeutic concentrations 1-3 hours after use.

The substance is destroyed in the liver and excreted from the body in the urine.

The half-life is 15-30 hours. The medicine is produced in tablets, in ampoules for intravenous and intramuscular injections. Tizercin tablets are white, odorless, coated. The drug is packaged in 50 pieces. The polyethylene lid is tamper evident. The tablet contains 25 mg of levomepromazine.

When is Tizercin prescribed?

Indications for prescribing an antipsychotic are the elimination of pain, the reduction of psychomotor agitation of various nature, and the treatment of mental disorders. Tizercin is also used to enhance the effect of analgesics.

Levomepromazine is prescribed for the treatment of pain in:

• herpes zoster;
• inflammation of the trigeminal nerve;
• damage to the facial nerve.

The drug is prescribed primarily in a neurological clinic. A doctor can prescribe levomepromazine tablets on an outpatient basis to treat insomnia, neurotic disorders, increased anxiety, and pain caused by neuritis.

Tizercin is used in the composition complex therapy diseases associated with psychomotor agitation, mental disorders:

There is a positive analgesic effect in the treatment of itchy dermatoses - skin diseases accompanied by itching.

Instructions for use

The medicine is used only as prescribed by a doctor. In the first days of use, a minimum dosage of 25-50 mg is prescribed. Take the medicine during the day, distributing Tizercin so that most of it falls in the evening.

In subsequent days, the daily dosage is gradually increased, increasing by 50-75 mg, until the dose reaches the average daily norm of 200-300 mg.

When the patient's condition improves, the daily dosage is reduced, selecting a maintenance dose for each patient individually. Tablets are not used to treat acute mental disorders. With exacerbation of psychoses, anxiety disorders, panic attacks Levomepromazine solution is prescribed intravenously or intramuscularly.

In a small dosage, the tablet preparation is used to treat outpatients with neurotic disorders, insomnia. The daily dose is 12.5-50 mg. For pain due to neuritis, levomepromazine is prescribed in a dosage of 50-200 mg.

Signs of a pill overdose

Overdose is possible with long-term use of the medicine in large doses. The first signs of an overdose of Tizercin are a decrease in blood pressure, confusion, fever. If you do not provide first aid to the victim, then epileptic seizures develop, extrapyramidal symptoms appear.

Do not try to induce vomiting in the patient because of the risk of an epileptic seizure. Gastric lavage is recommended if the victim is conscious.

It is necessary to call the doctors, and while waiting for the doctors, the patient can be given enterosorbents to slow down the absorption of levomepromazine if the tablet was taken less than 1 hour ago.

If more than 1-2 hours have passed after taking Tizercin, then the patient can be given a laxative to speed up the evacuation of the intestinal contents.

Contraindications and side effects

Although levomepromazine is most often well tolerated by patients, this psychoactive compound can cause side effects. Among side effects provoked by taking pills, extrapyramidal disorders of the nervous system are most common.

Extrapyramidal disorders are manifested by movement disorders:

• chorea - erratic movements and gestures;
• parkinsonism - increased muscle tone;
• tics - involuntary twitching muscles;
• tremor - small amplitude oscillatory movements of body parts;
• dystonia - spasm of antagonist muscles;
• amymia - lack of facial expressions due to damage to the facial nerve;
• akathisia - an irresistible need to move, change position;
• athetosis - slow, pretentious movements of the limbs, grimacing.

Side effects include confusion and slurred speech. The most dangerous brain disorder is neuroleptic malignant syndrome. This rare condition is characterized by an acute disturbance of consciousness, which can lead to coma.

Side effects of the tablets are also observed in the following organs:

1. Digestive tract. Dry mouth, constipation appear, and liver function is disrupted.
2. Heart and blood vessels. The patient's heart rate increases and orthostatic hypotension develops.
3. Hematopoietic organs. The number of platelets and neutrophils in the blood decreases, and susceptibility to bacterial and fungal infections increases.
4. Urinary system. Urine becomes discolored and urination is impaired.
5. Endocrine system. The menstrual cycle is disrupted, galactorrhea occurs, and there is evidence that the risk of pituitary adenoma increases.
6. Leather. The appearance of erythema and photosensitivity is noted.

Taking it can provoke allergic reactions in the form of urticaria, Quincke's edema, and anaphylactic shock. A side effect of the tablets can be an increase in temperature, pigmentary retinopathy - a disease that causes deterioration of blood supply to the retina of the eye, which can lead to blindness.

Who are the tablets contraindicated for?

Contraindications for Tizercin include organ diseases that cause side effects. If the patient suffers from heart disease accompanied by arrhythmia, then levomepromazine is contraindicated. You should not take an antipsychotic if you have retinal pathologies or Parkinson's disease.

Tablets are not prescribed to patients suffering from:

• heart failure;
• hypotension;
• angle-closure glaucoma;
• multiple sclerosis;
• renal, hepatic pathology;
• porphyria;
• granulocytopenia.

Older people should not take pills without medical supervision. The drug is prohibited for children under 12 years of age, pregnant women and women during lactation. If it is necessary to take levomepromazine, on the recommendation of a doctor, stop breastfeeding for the duration of treatment.

Drug interactions

The medicine should not be used in combination with drugs that lower blood pressure. Concomitant use increases the risk of severe side effects. Antipsychotics should be prescribed with caution in combination with the following drugs:

1. Inhibiting the activity of the nervous system. Tranquilizers, sleeping pills, and narcotic analgesics enhance inhibition processes.
2. Increases brain activity. The effectiveness of amphetamine and methamphetamine is reduced.
3. Levodopa. The effect of the medicine is weakened.
4. Anticholinergic drugs. The side effects of atropine and scopalamine intensify, causing glaucoma and intestinal obstruction.
5. Medicines that change ECG length QT. Macrolides, antiarrhythmics, a number of antimycotics, antidepressants, diuretics, antihistamines, when taken simultaneously with levomepromazine, prolong the QT, provoking arrhythmia.

Under medical supervision, Tizercin is taken with antacids, which are prescribed for stomach diseases. These drugs slow down the absorption of levomepromazine, which reduces its effectiveness. Alcohol and drugs that increase photosensitivity should not be taken with Tizercin tablets.

Predisposition to sunburn increases with the simultaneous use of tetracyclines, fluoroquinolones, oral contraceptives, some cardiac medications, sleeping pills, antidepressants, and vitamins.

While taking the drug, you must observe bed rest for 1.5 hours after taking the medication, since the use of an antipsychotic can cause orthostatic collapse. This phenomenon is that with a sudden change in body position, a decrease in blood pressure is possible, causing blood to flow away from the head and fainting.

Stop taking the medication immediately if signs of allergy or neuroleptic malignant syndrome appear. It is also necessary to stop treatment in cases of nausea, insomnia, and trembling of the limbs.

If negative changes occur as a result of long-term treatment, then the drug is discontinued, gradually reducing the dosage.

After stopping taking the pills, patients may experience “early activation” syndrome.

The syndrome is manifested by a sudden feeling of a surge of energy and the appearance of insomnia. The drug causes drowsiness during the day, which must be taken into account when working with moving mechanisms. It is unacceptable to drink alcohol within 5 days after treatment with levomepromazine.

During treatment you need to monitor your blood pressure, blood count, heart and liver condition.

Analogues and substitutes of the drug

Analogues of Tizercin based on the active substance levomepromazine include the powder-substance Levomepromazine maleate. This medicine is packaged in plastic bags of 1 kg, 10 kg, and is intended for hospitals. Analogs in terms of effect include drugs with the names Aminazine, Propazine, Chlorpromazine hydrochloride.

All Tizercin analogues are prescribed by a psychotherapist; they can only be ordered by prescription. Medicines can cause side effects and have a number of contraindications for diseases of the heart, blood vessels, and kidneys. The closest analogue of Tizercin is Aminazine.

Pros and cons of Tizercin

For outpatient patients, Tizercin is most often prescribed for the treatment of depression and persistent insomnia. Improvement is observed in most patients after 2 weeks. In the hospital, the medicine is used in the complex treatment of psychomotor agitation and mental disorders.

The antipsychotic drug causes side effects, and an overdose can be fatal. An exceptional danger is posed by simultaneous use of the drug with alcohol, sleeping pills and antihypertensive drugs. Tablets are prohibited for children under 12 years of age; they are prescribed with caution in the elderly.

Analogue of Tizercin tablets

Tizercin (tablets) 29

Manufacturer: Egis (Hungary)
Release forms:

• Tab. p/obol. 25 mg, 50 pcs.; Price from 181 rubles

Prices for Tizercin in online pharmacies
Instructions for use
Valenta Pharmaceutics (Russia) Aminazine is another domestically produced antipsychotic. Also sold in tablet form, but contains other active substance(chlorpromazine) in a dosage of 25 to 100 mg. Aminazine package is much cheaper, but it contains only 10 tablets, while Propazine contains 50 of them. The average cost of both drugs is approximately the same, so Aminazine will be beneficial only for short-term use, when you need less than 50 tablets per course of treatment.

Analogs of the drug Tizercin

Aminazine (dragée) 20

Analogue is cheaper from 59 rubles.

Manufacturer: Valenta Pharmaceuticals (Russia)
Release forms:

• Dragee 25 mg, 10 pcs.; Price from 122 rubles

Prices for Aminazine in online pharmacies
Instructions for use
Aminazine is another domestically produced antipsychotic. Also sold in tablet form, but contains another active ingredient (chlorpromazine) at a dosage of 25 to 100 mg. Aminazine package is much cheaper, but it contains only 10 tablets, while Propazine contains 50 of them. The average cost of both drugs is approximately the same, so Aminazine will be beneficial only for short-term use, when you need less than 50 tablets per course of treatment.

Propazine (tablets) 18

The analogue is more expensive from 497 rubles.

Manufacturer: Tatkhimpharmpreparaty (Russia)
Release forms:

• Tab. 25 mg, 50 pcs.; Price from 678 rubles

Prices for Propazine in online pharmacies
Instructions for use
Propazine is a domestically produced neuroleptic, produced in the form of tablets containing promazine in a dosage of 25 or 50 mg. It can be prescribed for acute and chronic psychoses, manic states, neurosis, fear, insomnia and other diseases of the nervous system. Propazine contains enough big list contraindications and restrictions, therefore, before starting to take the medicine, we strongly recommend that you consult with a specialist.

DiscussionAdd a review / ask a question

More medicines from this manufacturer:

Analogs of Albarel tablets
Solution analogs Betadine
Analogues of tablets Velaksin
Analogues of tablets Galidor
Analog candles Zalain
Analogs of Cordaflex RD tablets
Analogs of Cardilopin tablets
Analogues of Melipramine tablets
Analogues of Noflux tablets
Analogues of tablets Rileptid
Analogues of Setegis tablets
Analogs of Suprastin tablets
Analogues of tablets Sorbifer Durules
Analogs of Suprastinex tablets
Analogues of tablets Hartil
Analogs of tablets Ereksezil
Analogues of tablets Egithromb
Analogues of tablets Egilok
Analog tablets Alzepil
Analogue of tablets Lucetam
Analog tablets Parlazin
Egolanza tablets analogue
Analog tablets Stimuloton
Analogue of Halixol tablets
Analogue Betadine
Analogue of Rozulip tablets
Analogue of Ketilept tablets
Analogue of Visken tablets
Analog of Betadine ointment
Analogue of Zalain cream
Analogue of Tulosin capsules
Analogue of Pipolfen dragee
Analogue of Suprastin solution
>Tizercin

• One tablet of Tizercin contains 25 mg of levomepromazine. Additional substances: sodium starch glycolate, magnesium stearate, potato starch, microcrystalline cellulose, povidone, lactose. Shell composition: magnesium stearate, titanium dioxide, dimethicone, hypromellose.
• One milliliter of Tizercin solution contains 25 mg of levomepromazine. Additional substances: sodium chloride, monothioglycerol, anhydrous citric acid, water.

Release form

• White, biconvex, round, odorless tablets. 50 tablets in a brown glass bottle with an accordion shock absorber and initial opening control - one such bottle in a cardboard pack.
• Colorless transparent solution with a specific odor. 1 ml of solution in a glass ampoule with a break point - five ampoules in a contour package - two packages in a cardboard box.

>Pharmacological action

Antipsychotic, antihistamine, antiemetic, sedative, hypothermic, analgesic, m-anticholinergic effect.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Phenothiazine-type neuroleptic. It has antipsychotic, antiemetic, sedative, hypothermic, antihistamine, analgesic, and anticholinergic effects. Reduces blood pressure.

The antipsychotic effect is caused by blockade of D2-dopamine receptors in the mesocortical and mesolimbic systems of the brain.

The sedative effect is caused by the blockade of adrenaline receptors in the reticular formation of the brain; hypothermic – blockade of hypothalamic dopamine receptors; antiemetic - blockade of D2-dopamine receptors of the vomiting center. Extrapyramidal side effects are less pronounced with levomepromazine than with “classical” antipsychotics.

Increases the pain threshold. Due to its ability to enhance the effect of analgesics, anesthesia drugs and antihistamines, Tizercin can be used for complementary therapy with pain syndrome. The greatest analgesic effect is achieved within 40 minutes after intramuscular administration and lasts four hours.

Pharmacokinetics

After oral administration, the highest concentration is recorded in the blood after an average of 2 hours, and after intramuscular administration - after 60 minutes.

Actively penetrates through any histohematic barriers, distributed in various organs and fabrics. It is rapidly transformed in the liver, undergoing demethylation with the formation of final glucuronide and sulfate conjugates, which are evacuated in the urine. N-desmethylomono-methotrimeprazine is the only metabolite with pharmacological activity; other metabolites are inactive.

The half-life is approximately 20-25 hours. A small part of the dose taken (up to 1%) is excreted in its original form in urine and feces.

Indications for use

• Psychomotor agitation in psychosis, bipolar disorders, mental retardation, schizophrenia, epilepsy.
• Other mental disorders complicated by anxiety, agitation, phobias, panic, persistent insomnia.
• The need to enhance the effects of analgesics, drugs for general anesthesia, H1-histamine receptor inhibitors.
• Pain syndrome (inflammation of the facial nerve, trigeminal neuralgia, herpes zoster).

• overdose of drugs that have a suppressive effect on the nervous system (general anesthetics, alcohol, sleeping pills);
• concomitant use of antihypertensive drugs;
• angle-closure glaucoma;
• Parkinson's disease;
• multiple sclerosis;
• hemiplegia;
• myasthenia gravis;
• urinary retention;
• chronic cardiac failure in the stage of decompensation;
• severe liver or kidney failure;
• suppression of bone marrow hematopoiesis;
• severe arterial hypotension;
• lactation;
• porphyria;
• hypersensitivity to the components of the drug or other phenothiazines;
• age less than 12 years.

The drug is used with caution in epilepsy, in old age, and in people with a history of cardiac diseases.

Side effects

• Circulatory phenomena: orthostatic hypotension, decreased blood pressure, Adams-Stokes syndrome, increased QT interval, tachycardia. When using phenothiazine antipsychotics, cases of sudden death are known.
• Hematopoietic phenomena: agranulocytosis, pancytopenia, leukopenia, thrombocytopenia, eosinophilia.
• Nervous effects: dizziness, drowsiness, fatigue, visual hallucinations, confusion, increased intracranial pressure, catatonia, slurred speech, extrapyramidal symptoms, disorientation, epileptic seizures.
• Metabolic phenomena: changes in the menstrual cycle, galactorrhea, weight loss, mastalgia. The development of pituitary adenomas has been reported in a number of patients using phenothiazine derivatives, but more research is needed to prove a cause-and-effect relationship.
• Phenomena from the genitourinary system: discoloration of urine, difficulty urinating, impaired uterine contractions.
• Digestive symptoms: abdominal discomfort, dry mouth, vomiting, nausea, constipation, liver damage.
• Skin phenomena: hyperpigmentation, erythema, photosensitivity.
• Visual effects: pigmentary retinopathy.
• Allergic reactions: peripheral edema, laryngeal edema, bronchospasm, urticaria, anaphylactoid reactions, exfoliative dermatitis.
• Other phenomena: hyperthermia, pain and swelling in the injection area.

Instructions for use of Tizercin (Method and dosage)

The instructions for use of Tizercin allow the drug to be administered orally, starting from 25-50 mg per day, divided into several doses. The dose is increased by 25-50 mg daily until the condition improves. In patients who are insensitive to other antipsychotics, the daily dose is allowed to be increased by 50-75 mg per day. Average doses are 200-300 mg per day. After improvement and stabilization of the condition, the dose should be reduced to maintenance (determined individually).

For patients with neurotic disorders in outpatient practice, the drug is prescribed at a dose of 12.5-50 mg per day.

Parenteral use

This delivery route is used when it is not possible to take the drug orally. The daily dose is usually 75-100 mg and is divided into 2-3 injections, which are carried out in bed rest and under the control of blood pressure and pulse. If necessary, the daily dose is increased to 200-250 mg.

The solution can be administered deeply intramuscularly or intravenously. For intravenous drip infusion, 50-100 mg of the drug must be diluted in 250 ml of saline or 5% glucose solution and slowly administered through a dropper.

Signs of overdose: decreased blood pressure, conduction disturbances, hyperthermia, depression of consciousness up to coma, sedation, extrapyramidal symptoms, epileptic seizures.

Treatment of overdose: monitoring and correction of fluid balance, electrolytes and acid-base balance, kidney function, diuresis, liver enzyme concentrations, ECG. Symptomatic treatment is carried out based on an assessment of the results of the above indicators. When pressure decreases, intravenous fluid administration, Trendelenburg position, and administration of Dopamine or Norepinephrine are indicated. It is recommended to provide conditions for resuscitation due to the proarrhythmogenic effect of levomepromazine.

In case of overdose of antipsychotics, it is not recommended to use Adrenaline, Lidocaine and long-acting arrhythmic drugs. To treat seizures, Diazepam or Phenytoin is prescribed (for recurrent seizures). When rhabdomyolysis develops, Mannitol is administered. There is no selective antidote.

It is not recommended to induce artificial vomiting, since epileptic convulsions and dystonic movements of the muscles of the head or neck can lead to the penetration of vomit into the respiratory tract.

Gastric lavage is performed with monitoring of vital signs. Additional suppression of drug absorption is achieved by using enterosorbents and laxatives.

Interaction

Antihypertensive drugs and MAO inhibitors should not be used simultaneously with Levomepromazine.

• m-anticholinergic drugs (H1-histamine receptor inhibitors, tricyclic antidepressants);
• a number of antiparkinsonian drugs;
• Scopolamine, Atropine, Suxamethonium;
• drugs that suppress the nervous system (general anesthesia, opioid analgesics, sedatives and hypnotics, anxiolytics, tricyclic antidepressants, tranquilizers);
• drugs that stimulate the nervous system (amphetamine derivatives and other drugs);
• Levodopa;
• hypoglycemic oral agents;
• drugs that increase the QT interval;
• drugs that cause photosensitivity;
• ethanol;
• antacids;
• drugs that suppress bone marrow hematopoiesis;
• Dilevalol (dosage reduction of both drugs may be required).

Levomepromazine and its non-hydroxylated derivatives are potent CYP2D6 blockers. Concomitant use with drugs metabolized by CYP2D6 leads to increased concentrations and increased undesirable effects.

>Terms of sale

On prescription.

>Storage conditions

Keep away from children. Store at room temperature in a dark place.

>Expiration date

special instructions

Combined use with MAO inhibitors, drugs that depress the nervous system, and m-anticholinergics requires extreme caution.

Tizercin should be prescribed with caution to patients with liver or kidney damage.

Elderly people are predisposed to the development of orthostatic hypotension, as well as to the sedative and anticholinergic effects of phenothiazines. They are more likely to experience extrapyramidal side effects.

In cases of parenteral use of the drug, the injection sites should be alternated, since local irritation and tissue changes may occur.

Caution must be exercised when using the drug in patients (especially the elderly) suffering from cardiac diseases, patients with congestive heart failure, arrhythmia, conduction disorders, and long QT syndrome.

If hyperthermia occurs during treatment with antipsychotics, it is necessary to exclude the possibility of neuroleptic malignant syndrome, which is life-threatening and is characterized by the following symptoms: confusion, hyperthermia, muscle rigidity, disruption of the autonomic system, increased activity of creatine phosphokinase, catatonia, myoglobinuria and acute renal failure. If such symptoms or hyperthermia of unknown origin occur, use of the drug should be stopped immediately.

After abrupt withdrawal of a drug used for a long time or in large doses, vomiting, nausea, tremor, headache, increased sweating, insomnia, tachycardia, anxiety, tolerance to sedative effect phenothiazine derivatives and cross-tolerance to other antipsychotics. For these reasons, Tizercin should always be discontinued gradually.

The development of cholestatic jaundice depends on the individual characteristics of the patient. This symptom completely disappears after stopping use of the drug, so long-term treatment requires constant monitoring of liver parameters.

Before and during treatment, it is necessary to regularly monitor the following indicators: liver function, leukocyte count, blood pressure, ECG (if cardiac diseases and in elderly patients), potassium content in the blood. It is also necessary to periodically monitor the ratio of plasma electrolytes and correct it.

During the initial period of treatment, operating mobile mechanisms is strictly prohibited. The duration of the ban is determined in each case individually.

>AnalogsMatches by level 4 ATX code:

Tizercin analogues: Aminazine, Chlorpromazine hydrochloride.

Not for use in children under 12 years of age. For children over 12 years of age, if indicated, dosages of 0.35-3 mg per kilogram of body weight per day are recommended.

>With alcohol

It is prohibited to combine the drug with alcohol-containing drinks.

>During pregnancy and lactation

During these periods, you should refrain from taking the drug.

Reviews of Tizercin

Reviews indicate that the drug has a powerful sedative effect in case of sleep disorders and severe agitation against the background of autism, schizophrenia and other mental pathologies.

There are frequent cases of individual insensitivity to the product. ABOUT side effects Rarely reported by patients. In outpatient practice, the use of Tizercin is limited due to the difficulty of selecting doses and monitoring the patient.

Tizercin price, where to buy

The price of a package of the drug in tablets in Russia starts from 245 rubles, and in Ukraine the price of tablets approaches 114 hryvnia.

• Online pharmacies in UkraineUkraine

Pharmacy24

• Tizercin 25 mg 1 ml No. 10 injection solution ZAT FZ EGIS/VAT Pharmaceutical plant EGIS, Ugorshchina/Ugorshchina 109 UAH.order
• Tizercin 25 mg No. 50 tablets ZAT FZ EGIS/VAT Pharmaceutical plant EGIS, Ugorshchina/Ugorshchina 95 UAH.order

PaniPharmacy

• Tizercin tablets Tizercin tablets. p/o 25 mg No. 50 Hungary, Egis 95 UAH. order
• Tizercin ampoule Tizercin solution d/in. 25mg amp. 1ml No. 10 Hungary, Egis 117 UAH. order

show more

Tizercin tablets - official* instructions for use

*registered by the Ministry of Health of the Russian Federation (according to grls.rosminzdrav.ru)
See where the instructions from MEDI RU were received Analogues, articles Comments

Registration number:

ПN011307/01-25.02.2010

Trade name of the drug:

Tizercin

INN:

levomepromazine

Dosage form:

film-coated tablets

Compound:

active substance: 25 mg levomepromazine (equivalent to 33.8 mg levomepromazine hydromaleate),
excipients: magnesium stearate 1 mg, sodium starch glycolate 2 mg, povidone 8 mg, microcrystalline cellulose 10 mg, potato starch 15.2 mg, lactose 40 mg, tablet shell: titanium dioxide 0.758 mg, hypromellose 2.632 mg, dimethicone 0.355 mg, magnesium stearate 0.255 mg.

Description:
Round, slightly biconvex, film-coated tablets, white, odorless

Pharmacotherapeutic group:

antipsychotic (neuroleptic)

ATX code: N05AA02

Pharmacodynamics:

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderate antihistamine and M-anticholinergic effects. Causes a decrease in blood pressure (BP).
The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems.
The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.
Extrapyramidal side effects of levomepromazine are less pronounced than those of “classical” antipsychotics. Levomepromazine increases the pain threshold. Due to the ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy in acute and chronic pain syndrome.

Pharmacokinetics:

The maximum concentration of the drug in the blood plasma is reached 1-3 hours after ingestion. Passes through histohematic barriers, including the blood-brain barrier, and is distributed in organs and tissues.
Levomepromazine is rapidly metabolized in the liver by demethylation to sulfate and glucuronide conjugates, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylomono-methotrimeprazine) has pharmacological activity, the remaining metabolites are inactive. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours.

Indications for use:

Psychomotor agitation of various etiologies:

• for schizophrenia (acute and chronic)
• for bipolar disorders
• for senile, intoxication and other psychoses
• for oligophrenia
• for epilepsy

as well as other mental disorders occurring with:

• agitation
• anxiety
• panic
• phobias
• persistent insomnia

Strengthening the action of analgesics, general anesthesia, antihistamines.

Pain syndrome (trigeminal neuralgia, neuritis of the facial nerve, herpes zoster).

Contraindications:

• simultaneous use of antihypertensive drugs,
• hypersensitivity to phenothiazines,
• overdose of drugs that cause CNS inhibition (alcohol, general anesthetics, sleeping pills),
• angle-closure glaucoma,
• urinary retention,
• Parkinson's disease,
• multiple sclerosis,
• myasthenia gravis, hemiplegia,
• chronic heart failure in the stage of decompensation,
• severe renal/liver failure,
• severe arterial hypotension,
• inhibition of bone marrow hematopoiesis (granulocytopenia),
• porphyria,
• lactation,
• children up to 12 years of age.

With caution: epilepsy, patients with a history of cardiovascular diseases, especially in old age (cardiac muscle conduction disorders, arrhythmias, congenital long QT interval syndrome).

Pregnancy and lactation

Pregnancy
The drug should not be used during pregnancy unless the risk to the fetus has been carefully weighed against the benefit to the mother.
Lactation
Levomepromazine passes into breast milk. In this regard, and in the absence of controlled studies, its use during breastfeeding is contraindicated. If it is necessary to take the drug during lactation, the issue of stopping breastfeeding should be decided.

Directions for use and dosage:

Orally, starting with a daily dose of 25-50 mg in several doses (the maximum part of the daily dose should be administered before bedtime), increasing it daily by 25-50 mg until the patient’s condition improves. In patients resistant to other antipsychotics, the daily dose can be increased more quickly by adding 50-75 mg per day. Average daily doses are 200-300 mg.
After the patient’s condition improves, the dose should be reduced to a maintenance dose, the amount of which is determined individually.
In outpatient practice, patients with neurotic disorders are prescribed a daily dose of 12.5-50 mg (1/2-2 tablets).
For patients with psychosis, with severe psychomotor agitation, it is advisable to begin therapy with levomepromazine with parenteral administration.
To prevent the development of orthostatic collapse during treatment, bed rest is required.

Side effect

The cardiovascular system:
the most common side effect is decreased blood pressure and orthostatic hypotension. Tachycardia, Morgagni-Adams-Stokes syndrome, prolongation of the QT interval (arrhythmogenic effect, tachycardia of the “pirouette” type) are also possible (see also section “Contraindications”).
Hematopoietic system:
pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.
Central nervous system:
confusion, slurred speech, extrapyramidal symptoms with a predominance of akineto-hypotonic syndrome, epileptic seizures, increased intracranial pressure, neuroleptic malignant syndrome (NMS).
Endocrine system and metabolism:
galactorrhea, menstrual disorders, weight loss. The development of pituitary adenoma has been described in some patients receiving long-term phenothiazines, but further research is needed to establish a causal relationship with these drugs.
Genitourinary system:
discoloration of urine, urination disorders.
Gastrointestinal tract:
dry mouth, abdominal discomfort, nausea, vomiting, constipation, liver damage (jaundice, cholestasis).
Skin reactions: photosensitivity, erythema, pigmentation.
Vision: with long-term use, deposits in the lens and cornea, pigmentary retinopathy.
Allergic reactions:
laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.
Others: hyperthermia (may be the first sign of NMS), pain and swelling at injection sites.

Overdose:

Symptoms:
Arterial hypotension, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the “pirouette” type, atrioventricular block), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures.
Treatment:
resuscitation measures, symptomatic therapy. A specific antidote is not known. Forced diuresis, hemodialysis and hemoperfusion are not effective.

Interaction with other drugs

The simultaneous use of the following drugs should be avoided:

• Antihypertensive due to the risk of a pronounced decrease in blood pressure.
• Monoamine oxidase inhibitors MAO, because it is possible to increase the duration of the effect of the drug Tizercin and the severity of its side effects.

Caution should be exercised when combined with the following:

• Anticholinergic drugs (tricyclic antidepressants; H1-histamine receptor blockers; some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma). When combined with scopolamine, extrapyramidal side effects were observed.
• CNS depressants (narcotic analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the inhibitory effect of the drug on the central nervous system.
• CNS stimulants (for example, amphetamine derivatives) - decreased psychostimulant effect.
• Levodopa: The effect of this drug is weakened.
• Oral antidiabetic drugs: Their effectiveness is reduced, requiring dose adjustment.
• Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and potassium-lowering diuretics) increase the risk of QT prolongation and therefore increase the risk of arrhythmia.
• Drugs that cause photosensitivity: this effect may be enhanced.
• Alcohol: increases central nervous system inhibition and increases the likelihood of extrapyramidal side effects.
• Antacids: reduce absorption in the gastrointestinal tract (levomepromazine should be prescribed 1 hour before or 4 hours after taking antacids).

special instructions

The use of the drug should be discontinued if an allergic reaction occurs.

During pregnancy, the drug should be prescribed after careful comparison of risks and benefits (see section "Pregnancy and lactation").

Concomitant use with CNS depressants, MAO inhibitors and anticholinergics requires special caution (see Interactions section).

Particular caution is needed when prescribing drugs to patients with renal and/or liver failure due to the risk of drug accumulation.

Elderly patients are predisposed to orthostatic hypotension and the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, low initial doses and their gradual increase are especially important in this category of patients.

To avoid the development of orthostatic hypotension, the patient should lie down for half an hour after the first dose. If dizziness occurs after administration of the drug, you should remain in bed after each dose.

If hyperthermia occurs during antipsychotic therapy, neuroleptic malignant syndrome (NMS) should be excluded. NMS is a deadly disease characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), increased concentrations of creatine phosphokinase (CPK), myoglobinuria (rhabdomyolysis) and acute renal failure . If they occur, as well as if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, administration of the drug Tizercin ® should be stopped immediately.

After sudden withdrawal of a drug used in high doses or for a long time, the following may occur: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety, as well as the development of tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually.

Many antipsychotics, including levomepromazine, can lower the seizure threshold and cause epileptiform EEG changes. Therefore, when selecting the dose of Tizercin in patients with epilepsy, clinical parameters and EEG should be constantly monitored.

The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function is required.

The consumption of alcoholic beverages should be prohibited during treatment and until the effects of the drug disappear (within 4-5 days after stopping the administration of Tizercin ®.

• arterial pressure,
• liver function (especially in patients with liver disease),
• blood formula,
• ECG (for cardiovascular diseases and elderly patients).

Driving cars and working with mechanisms

During the treatment period, you should refrain from driving a car and performing work associated with an increased risk of accidents.

Release form

Film-coated tablets 25 mg.
50 tablets in a brown glass bottle with a PE cap, with first opening control and accordion shock absorber.
1 bottle along with instructions for use in a cardboard box.

Shelf life

5 years.
Do not use after the expiry date stated on the packaging.

Storage conditions

The drug belongs to the list No. 1 of potent substances of the Standing Committee for Drug Control of the Ministry of Health of the Russian Federation.
Store at a temperature of 15-25° C, out of the reach of children.

Conditions for dispensing from pharmacies

With a doctor's prescription!

Manufacturer

JSC Pharmaceutical Plant EGIS,
1106 Budapest, st. Keresturi, 30-38 HUNGARY

Representative Office of CJSC "Pharmaceutical Plant EGIS" (Hungary)
Moscow 121108, Moscow, st. Ivan Franko, d. 8.

• Russian
• Kazakh

Tradename

Tizercin®

International non-proprietary name

Levomepromazine

Dosage form

Film-coated tablets, 25 mg

One tablet contains

active substance - levomepromazine 25 mg (equivalent to 33.8 mg levomepromazine maleate),

excipients: lactose monohydrate, potato starch, microcrystalline cellulose, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate,

shell composition: hypromellose, titanium dioxide (E 171), dimethicone (E-1049)

Description

Round, slightly biconvex, white, odorless, film-coated tablets

Pharmacotherapeutic group

Psychotropic drugs. Neuroleptics. Phenothiazines with a dimethylaminopropyl group. Levomepromazine.

ATX code N05AA02

Pharmacokinetics

After oral administration, maximum plasma concentration is achieved within 1-3 hours. The apparent volume of distribution of levomepromazine is 23-42 l/kg. Levomepromazine is rapidly metabolized to form sulfate and glucuronide conjugates, which are excreted in the urine. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours. Levomepromazine has linear kinetics in the range of 10-300 ng/ml.

Pharmacodynamics

Tizercin is an antipsychotic from the group of phenothiazine derivatives. Acting on dopamine receptors of the thalamus, hypothalamus, reticular formation, and limbic system, levomepromazine inhibits sensory stimulation. Reduces motor activity and has a strong sedative effect. In addition, it is an antagonist of other neurotransmitter systems (noradrenergic, serotonergic, histaminergic and cholinergic). Therefore, levomepromazine has antiemetic, antihistamine, antiadrenergic and anticholinergic effects. Levomepromazine is an analogue of chlorpromazine with a more pronounced effect of inhibition of psychomotor activity compared to chlorpromazine. Extrapyramidal side effects are less pronounced than with other antipsychotics. The drug is a strong alpha-adrenergic receptor antagonist, but has a weak anticholinergic effect. Levomepromazine increases the pain threshold (analgesic effectiveness is comparable to morphine) and has an amnestic effect. Due to its ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy in severe acute and chronic pain syndrome.

Acute psychoses with psychomotor agitation and severe anxiety:

- acute attack of schizophrenia

- other acute psychotic conditions

Adjuvant therapy for chronic psychoses:

- chronic schizophrenia

- chronic hallucinatory psychoses

The drug should be used strictly according to the doctor's prescription!

Treatment should begin with low doses, which can then be gradually increased depending on tolerability of the drug. After the patient's condition improves, the dose should be reduced to a maintenance dose, the value of which is determined individually. The duration of treatment is determined by the doctor individually, depending on clinical condition patient.

For psychoses, the recommended initial dose is 25-50 mg (1-2 tablets) 2 times a day daily. If necessary, the initial daily dose can be increased to 150-250 mg (in 2-3 doses). Subsequently, depending on the effect, it may be reduced until a maintenance dose is reached.

Elderly patients

Elderly patients are characterized by increased sensitivity to phenothiazine derivatives. Since 25 mg film-coated tablets do not guarantee an exact dosage regimen, this drug is contraindicated in the elderly (persons over 65 years of age).

Patients with impaired liver and kidney function

There are no data on the use of the drug in patients with impaired liver and kidney function, however, the drug should be used with extreme caution, as it is metabolized in the liver and excreted from the body in the urine.

There are no data on the frequency of adverse reactions.

- pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia

- anaphylactoid reactions, laryngeal edema, peripheral edema, asthma

- weight loss, vitamin deficiency, glucose intolerance, hyperglycemia, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion

- reactivation of psychotic symptoms, catatonia, confusion, disorientation, visual hallucinations, slurred speech, drowsiness

- epileptic seizures, increased intracranial pressure, extrapyramidal symptoms (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), withdrawal syndrome, confusion, delirium, convulsions

– deposits in the lens and cornea, pigmentary retinopathy

- tachycardia, Adams-Stokes syndrome, prolongation of the QT interval (proarrhythmogenic effect, spindle-shaped ventricular tachycardia)

- venous thromboembolism, including pulmonary embolism and deep vein thrombosis (the frequency of which is unknown)

- Heat stroke in hot, humid conditions

- nausea, vomiting, constipation, which can become very severe and cause paralytic ileus, abdominal discomfort, dry mouth, liver damage (jaundice, cholestasis)

- necrotizing enterocolitis, with possible death (in very rare cases)

— exfoliative dermatitis, urticaria, erythema, photosensitivity, hyperpigmentation

- coloration of urine, difficulty urinating

- withdrawal symptoms in newborns

- galactorrhea, menstrual irregularities, in very rare cases - impaired uterine contractility, priapism

- neuroleptic malignant syndrome, hyperpyrexia, asthenia

- orthostatic hypotension (with accompanying weakness, dizziness and fainting)

Single messages

- cases of sudden death, possibly cardiac origin, as well as cases of unexplained sudden death of patients receiving phenothiazine antipsychotics

- Pituitary adenoma has been described in some patients chronically receiving phenothiazines, but further research is needed to establish a causal relationship with these drugs

- hypersensitivity to phenothiazines or other components of the drug

- simultaneous use of antihypertensive drugs

- simultaneous use of monoamine oxidase inhibitors

- overdose of drugs that cause depression of the central nervous system (alcohol, general anesthetics, sleeping pills)

- angle-closure glaucoma

- urinary retention

- Parkinson's disease

- multiple sclerosis

myasthenia gravis, hemiplegia

- severe cardiomyopathy (poor circulation)

- severe impairment of kidney or liver function

- severe arterial hypotension

- diseases of the hematopoietic organs

- porphyria

- acute infectious diseases of a viral, fungal or bacterial nature (including chicken pox, shingles); coma caused by intoxication with ethanol, drugs and sleeping pills

- lactation period

Elderly patients (over 65 children)

- children's age up to 18 years

Drug interactions

When levomepromazine is used concomitantly with drugs that are primarily metabolized by the cytochrome P450 2D6 enzyme system, the plasma concentrations of these drugs may increase, which may prolong or increase the effect or side effects of these drugs.

The simultaneous use of Tizercin with the following drugs:

- antihypertensive due to the risk of severe arterial hypotension

- monoamine oxidase inhibitors, since it is possible to increase the duration of the effect of Tizercin and the severity of its side effects.

Extreme caution should be exercised when combined with the following drugs:

- anticholinergic drugs (tricyclic antidepressants; H1-antihistamines; some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma); when combined with scopolamine, extrapyramidal side effects were observed

- drugs that depress the central nervous system (narcotic analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the effect of the drug on the central nervous system

- drugs that stimulate the central nervous system (for example, amphetamine derivatives) there is a decrease in the psychostimulant effect

- levodopa weakens the effect of this drug

- oral antidiabetic drugs: their effectiveness is reduced and hyperglycemia may occur

- drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, as well as the indirect effect of potassium-lowering diuretics); these effects can add up and increase the risk of arrhythmias

— dilevalol: by mutual inhibition of metabolism, this drug and Tizercin enhance each other’s effects; when used together, it may be necessary to reduce the dose of one or both drugs; a similar interaction with other beta-blockers is not excluded

- drugs that cause photosensitivity, due to the risk of increasing it

- ethanol: the inhibitory effect on the central nervous system increases and the likelihood of developing extrapyramidal side effects increases.

— simultaneous administration with vitamin C reduces the deficiency of this vitamin associated with the use of Tizercin

- simultaneous use of desferrioxyamine with prochlorperazine causes transient metabolic encephalopathy with loss of consciousness lasting from 48 to 72 hours. Such an interaction is also possible with levomepromazine, since its pharmacological activity is largely similar to that of prochlorperazine.

- adrenaline (epinephrine) should not be used in case of overdose of antipsychotics

The use of the drug should be discontinued immediately if any hypersensitivity reaction occurs.

Particular caution is required when prescribing the drug to patients with renal and/or liver failure due to the risk of accumulation and toxicity.

In randomized, placebo-controlled clinical trials in elderly patients with dementia treated with certain atypical antipsychotic drugs, a 3-fold increased risk of developing cerebrovascular accidents was observed. The mechanism for this increased risk is unknown. An increased risk of developing cerebrovascular accidents cannot be excluded for other antipsychotics or other patient groups. Tizercin should be used with caution in patients with risk factors for stroke.

Increased mortality in older patients with dementia

Two observational clinical studies showed that the use of antipsychotics in older patients with dementia had a small increased risk of mortality compared with untreated patients. These data are insufficient to accurately assess the risk, and the mechanism by which the risk increases is also unknown.

The use of Tizercin for the treatment of behavioral disorders in dementia is prohibited.

Elderly patients (especially those with dementia) have a greater predisposition to orthostatic hypotension and are also more sensitive to the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, in elderly patients the drug is prescribed with low initial doses and dose increases should be gradual.

Caution is recommended when treating patients with a history of cardiovascular disease, especially in the elderly, as well as those with congestive heart failure, conduction disorders, arrhythmias, congenital long QT syndrome or unstable circulatory system. Before starting the use of Tizercin, an electrocardiogram should be recorded to exclude any cardiovascular disease that may serve as a contraindication.

As with other phenothiazines, levomepromazine may cause QT prolongation, arrhythmias and, very rarely, torsade de pointes (TdP).

Cases of venous thromboembolism (VTE) have been observed during antipsychotic therapy. Since patients receiving antipsychotic drugs often have risk factors for acquired VTE, all possible risk factors should be identified and appropriate measures taken. preventive measures before and during treatment with Tizercin.

Hyperglycemia or glucose intolerance has been observed in patients. receiving levomepromazine. Patients with an established diagnosis diabetes mellitus or with risk factors for diabetes who are prescribed treatment with levomepromazine, appropriate glycemic monitoring should be carried out throughout treatment.

If hyperthermia occurs during treatment with antipsychotic drugs, neuroleptic malignant syndrome (NMS) should be excluded. NMS is a deadly disease characterized by the following symptoms: muscle rigidity, hyperthermia, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), catatonia. Laboratory findings: increased creatine phosphokinase (CPK) levels, myoglobinuria (rhabdomyolysis) and acute renal failure. All these symptoms indicate the development of NMS. If they occur, as well as if hyperthermia of unknown etiology occurs during treatment without pronounced clinical symptoms of NMS, the use of Tizercin should be stopped immediately. If, after recovery from NMS, the patient's condition requires further antipsychotic therapy, the choice of drug should be carefully considered.

Tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics have been described in the literature. Such tolerance may explain the signs functional disorders occurring after sudden withdrawal of high or long-term doses: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety. Therefore, discontinuation of the drug must be done gradually.

Many antipsychotics, including levomepromazine, can lower the epileptic seizure threshold and cause epileptiform electroencephalogram (EEG) changes. Therefore, when gradually adjusting the dose of Tizercin in patients with epilepsy, clinical parameters and EEG should be constantly monitored.

The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function indicators is recommended.

Agranulocytosis and leukopenia have also been observed in some patients treated with phenothiazines. Therefore, during long-term therapy, regular monitoring of the blood count is recommended, despite the very low frequency of these phenomena.

It is prohibited to consume alcoholic beverages during treatment and until the effects of the drug disappear (within 4-5 days after stopping the use of Tizercin).

- blood pressure (especially in patients with an unstable circulatory system and a predisposition to hypotension)

- liver function indicators (especially in patients with liver disease)

- blood count (for fever and pharyngitis, as well as for signs of leukopenia and agranulocytosis, at the beginning of the course of treatment and during long-term therapy)

- electrocardiogram (for cardiovascular diseases and in elderly patients).

- the level of potassium in the blood (periodic monitoring and correction of the level of electrolytes in the blood, especially with long-term, chronic use of the drug).

If the drug is suddenly discontinued, symptoms may develop. acute symptoms withdrawal, e.g. return of psychotic symptoms, restlessness, worsening of anxiety symptoms, insomnia, nausea, vomiting, headache, trembling, sweating, increased heart rate.

Since Tizercin 25 mg film-coated tablets contain 40 mg lactose monohydrate per tablet, it should not be administered to patients with hereditary galactose intolerance, Lapp-lactase deficiency, glucose-galactose malabsorption.

Pregnancy and lactation

If antipsychotics (including levomepromazine) were used in the third trimester of pregnancy, then after delivery the newborn is at risk of developing side effects, for example, extrapyramidal symptoms and / or withdrawal symptoms of varying duration and severity. There have been cases with the development of agitation, hypertension, hypotension, tremor, drowsiness, respiratory distress, as well as reports of side effects with malnutrition. Thus, careful monitoring of the condition of newborns should be carried out.

The drug should not be used during pregnancy unless a careful comparison of risk and benefit has been made. Levomepromazine is excreted in breast milk. In this regard, its use during lactation is contraindicated.

Features of influence medicine on the ability to manage vehicle or potentially dangerous mechanisms

Tizercin may cause drowsiness, disorientation, confusion, or significant hypotension, which may affect the patient's ability to drive. During the treatment period, patients are advised to refrain from driving a vehicle or potentially dangerous machinery. In the future, the degree of restrictions should be set for each patient individually.

Symptoms: changes in vital physiological parameters (often arterial hypotension and hyperthermia), conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia / fibrillation, torsades de pointes, atrioventricular block), extrapyramidal symptoms, sedation, excitation of the central nervous system (epileptic seizures) and NNS.

Treatment: monitoring of the following parameters: acid-base balance, water-electrolyte balance, kidney function, urine volume, liver enzyme activity, electrocardiogram. In patients with NMS, serum CPK and body temperature should be monitored. In accordance with the values ​​of the monitored parameters, symptomatic treatment should be prescribed. With arterial hypotension: intravenous administration fluids, Trendelenburg position, dopamine and / or norepinephrine (due to the proarrhythmic effect of levomepromazine, it is necessary to have a resuscitation kit ready and monitor the work of the heart).

In case of an overdose of neuroleptics, adrenaline should not be used. Lidocaine (lignocaine) and, if possible, long-acting antiarrhythmic drugs should be avoided. At convulsive states you can enter diazepam, and with the resumption of convulsions against the background of diazepam - phenytoin or phenobarbital. For rhabdomyolysis, mannitol should be given. A specific antidote is not known. Forced diuresis, hemodialysis and hemoperfusion are not effective. It is not recommended to induce vomiting, as possible epileptic seizures and dystonic reactions of the head and neck can lead to aspiration of vomit. Gastric lavage and monitoring of vital signs should be performed even 12 hours after dosing, since gastric emptying is slowed by the anticholinergic effect of levomepromazine. To further reduce absorption, the introduction of activated charcoal and laxatives is recommended.

Release form and packaging

50 film-coated tablets are placed in a brown glass bottle with an FG-7 polyethylene cap, tamper evident and equipped with an accordion shock absorber. The bottle is labeled with self-adhesive paper. 1 bottle, along with instructions for medical use in the state and Russian languages, is placed in a cardboard pack.

Store at a temperature not exceeding 25 oC.

Keep out of the reach of children!

Shelf life

Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription

JSC "EGIS PHARMACEUTICAL PLANT"

1106 BUDAPEST, st. Keresturi, 30-38 Hungary

Phone: (36-1) 803-5555, Fax: (36-1) 803-5529

Registration Certificate Holder

CJSC Pharmaceutical Plant EGIS, Hungary

Address of the organization that accepts claims from consumers regarding the quality of products (products) on the territory of the Republic of Kazakhstan

Representative office in the Republic of Kazakhstan of JSC "EGIS Pharmaceutical Plant"

050060, Almaty, st. Zharokova 286 G

Pharmacodynamics:

Antipsychotic drug (neuroleptic) of the phenothiazine series. It has antipsychotic, sedative (hypnotic), analgesic, moderate antiemetic, hypothermic, moderately blocks H1-histamine and M-cholinergic receptors. Causes a decrease in blood pressure (BP).
The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems.
The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus.
Extrapyramidal side effects of levomepromazine are less pronounced than those of “typical” antipsychotics. Levomepromazine increases the pain threshold. Due to its ability to enhance the effects of non-narcotic analgesics, this drug can be used for adjuvant therapy for acute and chronic pain syndrome.
The maximum analgesic effect develops within 20-40 minutes after intramuscular administration and lasts approximately 4 hours.

Pharmacokinetics:

After intramuscular administration, the maximum concentration in the blood plasma is reached after 30-90 minutes. Passes through histohematic barriers, including the blood-brain barrier, and is distributed in organs and tissues.
Levomepromazine is rapidly metabolized in the liver by demethylation to form conjugates with sulfuric or glucuronic acid, which are excreted in the urine. The metabolite formed as a result of demethylation (N-desmethylmonomethotrimeprazine) has pharmacological activity, the remaining metabolites are inactive. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours.

Indications for use

Psychomotor agitation of various etiologies

• for schizophrenia (acute and chronic)
• for bipolar disorders
• for senile, intoxication and other psychoses
• for oligophrenia
• for epilepsy

as well as other mental disorders occurring with

• agitation
• anxiety
• panic
• phobias
• persistent insomnia

Enhancing the effect of analgesics, general anesthesia, H1-histamine receptor blockers

Pain syndrome (trigeminal neuralgia, neuritis of the facial nerve, herpes zoster).

Contraindications

• simultaneous use of antihypertensive drugs,
• hypersensitivity to the components of the drug and phenothiazine derivatives,
• overdose of drugs that cause inhibition of the central nervous system (alcohol, general anesthesia, sleeping pills),
• angle-closure glaucoma,
• urinary retention,
• Parkinson's disease,
• multiple sclerosis,
• myasthenia gravis, hemiplegia,
• chronic heart failure in the stage of decompensation,
• severe renal/liver failure,
• severe arterial hypotension, inhibition of bone marrow hematopoiesis (granulocytopenia),
• porphyria,
• lactation,
• children up to 12 years of age.

CAREFULLY

Epilepsy, patients with a history of cardiovascular diseases, especially in old age (cardiac muscle conduction disorders, arrhythmias, congenital long QT syndrome). Pregnancy and lactation

Pregnancy and breastfeeding

The drug should not be used during pregnancy unless the risk to the fetus has been carefully weighed against the benefit to the mother. Levomepromazine passes into breast milk. In this regard, and in the absence of controlled studies, its use during breastfeeding is contraindicated.
If it is necessary to take the drug during lactation, the issue of stopping breastfeeding should be decided.

Directions for use and dosage

Parenteral administration is used when it is impossible to take the drug orally. The usual daily dose is 75-100 mg (for 2-3 injections) in bed rest under the control of blood pressure and pulse. If necessary, the daily dose is increased to 200-250 mg.
When administered intramuscularly, the drug should be injected deep into the muscle.
Intravenous drip infusions are also used, for which the drug Tizercin ® should be

Dilute

(50 - 100 mg of the drug in 250 ml of 0.9% sodium chloride solution or 5% dextrose (glucose) solution) and administer

Slowly through the IV

There is insufficient clinical experience with the parenteral use of levomepromazine in children under 12 years of age.
If there are strict indications for children over 12 years of age, doses ranging from 0.35 mg/kg/day to 3.0 mg/kg/day are recommended.

Side effect

From the cardiovascular system:
decreased blood pressure, orthostatic hypotension (with accompanying weakness, dizziness and loss of consciousness), Adams-Stokes syndrome, tachycardia, prolongation of the QT interval (arrhythmogenic effect, pirouette-type arrhythmia) (see section "Special instructions"). Cases of sudden death (possibly caused by cardiac causes) have been reported when taking phenothiazine antipsychotics.

From the circulatory system and lymphatic system:
pancytopenia, agranulocytosis, leukopenia, thrombocytopenia, eosinophilia.

From the central nervous system:
drowsiness, dizziness, increased fatigue, confusion, slurred speech, visual hallucinations, catatonia, disorientation, extrapyramidal symptoms with a predominance of akineto-hypotonic syndrome (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), epileptic seizures, increased intracranial pressure, malignant neuroleptic syndrome (NMS) (see also section “Special instructions”).

From the side of metabolism:
weight loss, galactorrhea, menstrual irregularities, mastalgia. Pituitary adenomas have been reported in some patients receiving phenothiazine derivatives, but further research is needed to establish a causal relationship between the use of these drugs and tumor development.

From the reproductive and urinary system:
difficulty urinating, discoloration of urine, impaired contractions of the uterine muscles.

From the gastrointestinal tract:
vomiting, nausea, constipation, discomfort in the abdominal area, dry mouth, liver damage (jaundice, cholestasis).

From the skin:
exfoliative dermatitis, urticaria, erythema, photosensitivity, hyperpigmentation.

From the organs of vision:
pigmentary retinopathy, deposits in the lens and cornea.

Allergic reactions:
laryngeal edema, peripheral edema, anaphylactoid reactions, bronchospasm, urticaria, exfoliative dermatitis.

Other: hyperthermia (may be the first sign of NMS), pain and swelling at the injection sites.

Overdose

Symptoms: decreased blood pressure, hyperthermia, conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia of the “pirouette” type, atrioventricular block), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, epileptic seizures, malignant neuroleptic syndrome.

Treatment: It is recommended to monitor the following indicators: acid-base balance, fluid and electrolyte balance, kidney function, urine volume, liver enzyme activity, ECG readings, and in patients with neuroleptic malignant syndrome - additionally serum CPK levels and body temperature. Symptomatic treatment should be carried out based on the results of the assessment of the above parameters. In case of decreased blood pressure, intravenous fluid replacement, Trendelenburg position, and the use of dopamine and/or norepinephrine are indicated. (Due to the pro-arrhythmogenic effect of levomepromazine, it is necessary to provide conditions for resuscitation, and when administering dopamine and/or norepinephrine, an ECG must be performed). In case of an overdose of antipsychotics, it is not recommended to use epinephrine (adrenaline).
The use of lidocaine (lignocaine) and, if possible, long-acting arrhythmic drugs should also be avoided.
To eliminate seizures, use diazepam or, for recurrent seizures, phenytoin or phenobarbitone. If rhabdomyolysis occurs, mannitol is prescribed.
There is no specific antidote.
Forced urination, hemodialysis and hemoperfusion are ineffective.
convulsions, dystonic reactions of the muscles of the head and neck can lead to vomit entering the respiratory tract. Gastric lavage, along with monitoring vital signs, is indicated even 12 hours after taking the drug, since its natural emptying is slow due to the m-anticholinergic effect of levomepromazine. An additional reduction in drug absorption is achieved by using activated carbon and laxatives.

Interaction with other drugs

The simultaneous use of levomepromazine and the following drugs should be avoided:

• Antihypertensive drugs due to the risk of a pronounced decrease in blood pressure.
• Monoamine oxidase inhibitors (MAO), because it is possible to increase the duration of action of levomepromazine and increase the severity of its side effects.

Caution should be exercised when used simultaneously with the following drugs:

• Drugs with m-anticholinergic activity (tricyclic antidepressants; H1-histamine receptor blockers; some antiparkinsonian drugs; atropine, scopolamine, suxamethonium) enhance the m-anticholinergic effect of levmepromazine (paralytic intestinal obstruction, urinary retention, glaucoma). When used concomitantly with scopolamine, extrapyramidal side effects were observed.
• CNS depressants (narcotic analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the inhibitory effect of levomepromazine on the central nervous system.
• CNS stimulants (eg, amphetamine derivatives): levomepromazine reduces their psychostimulant effect.
• Levodopa: Levomepromazine reduces the effect of levodopa.
• Oral hypoglycemic agents: when used simultaneously with levomepromazine, their effectiveness decreases, which requires dose adjustment.
• Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and potassium-lowering diuretics) increase the risk of QT prolongation and therefore increase the risk of arrhythmia. .
• Drugs that cause photosensitivity, when used simultaneously with levomepromazine, increase the likelihood of photosensitivity.
• Alcohol increases central nervous system inhibition and increases the likelihood of extrapyramidal side effects when used simultaneously with levomepromazine.
• Antacids reduce absorption in the gastrointestinal tract (levomepromazine should be prescribed 1 hour before or 4 hours after taking antacids).
• Drugs that inhibit bone marrow hematopoiesis increase the risk of myelosuppression.
• Dilevalol, like levomepromazine, inhibits metabolism, which leads to a mutual enhancement of the effect of both drugs. If they are used simultaneously, it may be necessary to reduce the dosage of one or both drugs. A similar interaction with other beta-blockers is possible.
• Levomepromazine and its non-hydroxylated metabolites are potent inhibitors of cytochrome P450 2D6. Concomitant use of levomepromazine with drugs primarily metabolized by cytochrome P450 2D6 may result in increased concentrations of these drugs, which may increase the undesirable effects of these drugs.

special instructions

The use of the drug should be discontinued if allergic reactions occur.
Concomitant use with central nervous system depressants, MAO inhibitors and anticholinergic blockers requires special caution (see section "Interaction with other drugs").
The drug should be prescribed with extreme caution to patients with impaired liver and/or kidney function.
Elderly patients are predisposed to orthostatic hypotension, as well as the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, treatment of these patients should be started with low doses and gradually increased.
In older people with dementia who were treated with antipsychotics, there was a small increase in the risk of mortality. There are insufficient data to determine the exact magnitude of the risk, and the reason for this increased risk is unknown. Tizercin® is not approved for use in the treatment of behavioral disorders associated with dementia.
To avoid the development of orthostatic hypotension, the patient should lie down for half an hour after the first dose. If dizziness occurs after administration of the drug, you should remain in bed after each dose until the dizziness disappears.
In cases of parenteral administration of the drug Tisercin®, the injection sites should, if necessary, be alternated, since the drug can cause local irritation and tissue damage.
It is also necessary to be careful when prescribing the drug to patients (especially the elderly) with a history of cardiovascular diseases, patients with congestive heart failure, conduction disorders, arrhythmia, and congenital long QT interval syndrome. Before starting treatment with Tizercin®, an ECG must be performed to exclude any cardiovascular disorder that may contraindicate the use of the drug.
There are reports of prolongation of the QT interval, the occurrence of arrhythmias and, very rarely, torsade de pointes (TdP) during therapy with phenothiazines (see section "Side effects").
If hyperthermia occurs during antipsychotic therapy, the possibility of neuroleptic malignant syndrome (NMS) should be excluded. This potentially life-threatening syndrome is characterized by the following symptoms: muscle rigidity, hyperthermia, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), catatonia, increased activity of creatine phosphokinase (CPK), myoglobinuria (rhabdomyolysis ) and acute renal failure. If they occur, and if hyperthermia of unknown etiology occurs during treatment without other clinical symptoms of NMS, the use of the drug Tizercin® should be stopped immediately.
After sudden withdrawal of a drug used in high doses or for a long time, the following may occur: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and anxiety, as well as the development of tolerance to the sedative effect of phenothiazine derivatives and cross-tolerance to various antipsychotics. For this reason, drug withdrawal should always be done gradually.
Many antipsychotics, including levomepromazine, can lower the seizure threshold and cause epileptiform ECG changes. For this reason, when titrating the dose of Tizercin®, all patients with epilepsy must ensure careful clinical observation and ECG monitoring.
The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the use of the drug. Therefore, during long-term treatment, regular monitoring of liver function is required.
Agranulocytosis and leukopenia have been reported in some patients receiving phenothiazines.
Despite the rarity of such cases, during long-term therapy with levomepromazine it is necessary to regularly monitor the leukocyte count.
During treatment and until the drug stops working (within 4-5 days after discontinuation of the drug), alcohol consumption is prohibited.
Before and during treatment, it is recommended to regularly monitor the following indicators: blood pressure, liver function (especially in patients with liver diseases), leukocyte blood count, ECG (for cardiovascular diseases and in elderly patients), serum potassium concentration. Periodic monitoring of the level of electrolytes in the blood and its correction is necessary (especially when planning long-term therapy).

Instructions for medical use

medicine

TIZERTSIN ®

Tradename

Tizercin ®

international generic name

Levomepromazine

Dosage form

Film-coated tablets, 25 mg

Compound

One tablet contains

active substance - levomepromazine 25 mg (equivalent to 33.8 mg levomepromazine maleate),

Excipients: lactose monohydrate, potato starch, microcrystalline cellulose, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate,

shell composition: hypromellose, titanium dioxide (E 171), dimethicone (E-1049)

Description

Round, slightly biconvex, white, odorless, film-coated tablets

Pharmacotherapeutic group

Psychotropic drugs. Neuroleptics. Phenothiazines with a dimethylaminopropyl group. Levomepromazine.

ATX code N05AA02

Pharmacological properties

Pharmacokinetics

After oral administration, maximum plasma concentration is achieved within 1-3 hours. The apparent volume of distribution of levomepromazine is 23-42 l/kg. Levomepromazine is rapidly metabolized to form sulfate and glucuronide conjugates, which are excreted in the urine. A small part of the administered dose (1%) is excreted unchanged in urine and feces. The half-life is 15-30 hours. Levomepromazine has linear kinetics in the range of 10-300 ng/ml.

Pharmacodynamics

Tizercin is an antipsychotic from the group of phenothiazine derivatives. Acting on dopamine receptors of the thalamus, hypothalamus, reticular formation, and limbic system, levomepromazine inhibits sensory stimulation. Reduces motor activity and has a strong sedative effect. In addition, it is an antagonist of other neurotransmitter systems (noradrenergic, serotonergic, histaminergic and cholinergic). Therefore, levomepromazine has antiemetic, antihistamine, antiadrenergic and anticholinergic effects. Levomepromazine is an analogue of chlorpromazine with a more pronounced effect of inhibition of psychomotor activity compared to chlorpromazine. Extrapyramidal side effects are less pronounced than with other antipsychotics. The drug is a strong alpha-adrenergic receptor antagonist, but has a weak anticholinergic effect. Levomepromazine increases the pain threshold (analgesic effectiveness is comparable to morphine) and has an amnestic effect. Due to its ability to enhance the effects of analgesics, this drug can be used for adjuvant therapy in severe acute and chronic pain syndrome.

Indications for use

Acute psychoses with psychomotor agitation and severe anxiety:

Acute attack of schizophrenia

Other acute psychotic conditions

Adjuvant therapy for chronic psychoses:

Chronic schizophrenia

Chronic hallucinatory psychoses

Dosage and administration

The drug should be used strictly according to the doctor's prescription!

Treatment should begin with low doses, which can then be gradually increased depending on tolerability of the drug. After the patient's condition improves, the dose should be reduced to a maintenance dose, the value of which is determined individually. The duration of treatment is determined by the doctor individually, depending on the clinical condition of the patient.

For psychoses, the recommended initial dose is 25-50 mg (1-2 tablets) 2 times a day daily. If necessary, the initial daily dose can be increased to 150-250 mg (in 2-3 doses). Subsequently, depending on the effect, it may be reduced until a maintenance dose is reached.

Elderly patients

Elderly patients are characterized by increased sensitivity to phenothiazine derivatives. Since 25 mg film-coated tablets do not guarantee an exact dosage regimen, this drug is contraindicated in the elderly (persons over 65 years of age).

Patients with impaired liver and kidney function

There are no data on the use of the drug in patients with impaired liver and kidney function, however, the drug should be used with extreme caution, as it is metabolized in the liver and excreted from the body in the urine.

Side effects

There are no data on the frequency of adverse reactions.

Pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia

Anaphylactoid reactions, laryngeal edema, peripheral edema, asthma

- weight loss, vitamin deficiency, glucose intolerance, hyperglycemia, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion

Reactivation of psychotic symptoms, catatonia, confusion, disorientation, visual hallucinations, slurred speech, somnolence

Epileptic seizures, increased intracranial pressure, extrapyramidal symptoms (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), withdrawal syndrome, confusion, delirium, convulsions

- deposits in the lens and cornea, pigmentary retinopathy

- tachycardia, Adams-Stokes syndrome, prolongation of the QT interval (proarrhythmogenic effect, fusiform ventricular tachycardia)

Venous thromboembolism, including pulmonary embolism and deep vein thrombosis (frequency unknown)

Heat stroke in hot, humid conditions

Nausea, vomiting, constipation, which can become very severe and cause paralytic ileus, abdominal discomfort, dry mouth, liver damage (jaundice, cholestasis)

Necrotizing enterocolitis, possibly fatal (in very rare cases)

- exfoliative dermatitis, urticaria, erythema, photosensitivity, hyperpigmentation

- coloration of urine, difficulty urinating

- withdrawal symptoms in newborns

Galactorrhea, menstrual irregularities, in very rare cases - impaired uterine contractility, priapism

Neuroleptic malignant syndrome, hyperpyrexia, asthenia

Often

Orthostatic hypotension (with associated weakness, dizziness and fainting)

Single messages

Cases of sudden death, possibly of cardiac origin, as well as cases of unexplained sudden death in patients receiving phenothiazine antipsychotics

Pituitary adenoma has been described in some patients chronically treated with phenothiazines, but further research is needed to establish a causal relationship with these drugs.

Contraindications

Hypersensitivity to phenothiazines or other components of the drug

Concomitant use of antihypertensive drugs

Concomitant use of monoamine oxidase inhibitors

Overdose of drugs that cause depression of the central nervous system (alcohol, general anesthetics, sleeping pills)

Angle-closure glaucoma

Urinary retention

Parkinson's disease

Multiple sclerosis

Myasthenia gravis, hemiplegia

Severe cardiomyopathy (poor circulation)

Severe impairment of kidney or liver function

Severe arterial hypotension

Diseases of the hematopoietic organs

Porphyria

Acute infectious diseases of a viral, fungal or bacterial nature (including chicken pox, shingles); coma caused by intoxication with ethanol, drugs and sleeping pills

Lactation period

Elderly patients (over 65 children)

Children under 18 years of age

Drug interactions

When levomepromazine is used concomitantly with drugs that are primarily metabolized by the cytochrome P450 2D6 enzyme system, the plasma concentrations of these drugs may increase, which may prolong or increase the effect or side effects of these drugs.

The simultaneous use of Tizercin with the following drugs is prohibited:

- antihypertensive due to the risk of severe arterial hypotension

Monoamine oxidase inhibitors, since it is possible to increase the duration of the effect of Tizercin and the severity of its side effects.

Extreme caution should be exercised when combined with the following drugs:

Anticholinergic drugs (tricyclic antidepressants; H 1 -antihistamines; some antiparkinsonian drugs; atropine, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma); when combined with scopolamine, extrapyramidal side effects were observed

Drugs that depress the central nervous system (narcotic analgesics, general anesthesia, anxiolytics, sedatives and hypnotics, tranquilizers, tricyclic antidepressants) enhance the effect of the drug on the central nervous system

Drugs that stimulate the central nervous system (for example, amphetamine derivatives) reduce the psychostimulant effect

Levodopa weakens the effect of this drug

Oral antidiabetic drugs: their effectiveness is reduced and hyperglycemia may occur

Drugs that prolong the QT interval (some antiarrhythmic drugs, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, some antihistamines, and the indirect effect of potassium-lowering diuretics); these effects can add up and increase the risk of arrhythmias

Dilevalol: by mutual inhibition of metabolism, this drug and Tizercin enhance each other’s effects; when used together, it may be necessary to reduce the dose of one or both drugs; a similar interaction with other beta-blockers is not excluded

Drugs that cause photosensitivity due to the risk of increasing it

Ethanol: the inhibitory effect on the central nervous system increases and the likelihood of developing extrapyramidal side effects increases.

Others:

- simultaneous administration with vitamin C reduces the deficiency of this vitamin associated with the use of Tizercin

Concomitant use of desferrioxyamine with prochlorperazine causes transient metabolic encephalopathy with loss of consciousness lasting 48 to 72 hours. Such an interaction is also possible with levomepromazine, since its pharmacological activity is largely similar to that of prochlorperazine.

Adrenaline (epinephrine) should not be used in case of overdose of antipsychotics

special instructions

The use of the drug should be discontinued immediately if any hypersensitivity reaction occurs.

Particular caution is required when prescribing the drug to patients with renal and/or liver failure due to the risk of accumulation and toxicity.

Stroke

In randomized, placebo-controlled clinical trials in elderly patients with dementia treated with certain atypical antipsychotic drugs, a 3-fold increased risk of developing cerebrovascular accidents was observed. The mechanism for this increased risk is unknown. An increased risk of developing cerebrovascular accidents cannot be excluded for other antipsychotics or other patient groups. Tizercin should be used with caution in patients with risk factors for stroke.

Increased mortality in older patients with dementia

Two observational clinical studies showed that the use of antipsychotics in older patients with dementia had a small increased risk of mortality compared with untreated patients. These data are insufficient to accurately assess the risk, and the mechanism by which the risk increases is also unknown.

The use of Tizercin for the treatment of behavioral disorders in dementia is prohibited.

Elderly patients (especially those with dementia) have a greater predisposition to orthostatic hypotension and are also more sensitive to the anticholinergic and sedative effects of phenothiazines. In addition, they are particularly prone to extrapyramidal side effects. Therefore, in elderly patients the drug is prescribed with low initial doses and dose increases should be gradual.

Caution is recommended when treating patients with a history of cardiovascular disease, especially in the elderly, as well as those with congestive heart failure, conduction disorders, arrhythmias, congenital long QT syndrome or unstable circulatory system. Before starting the use of Tizercin, an electrocardiogram should be recorded to exclude any cardiovascular disease that may serve as a contraindication.

As with other phenothiazines, levomepromazine may cause QT prolongation, arrhythmias and, very rarely, torsade de pointes (TdP).

Cases of venous thromboembolism (VTE) have been observed during antipsychotic therapy. Since patients receiving antipsychotic drugs often have risk factors for acquired VTE, all possible risk factors should be identified and the necessary preventive measures taken before and during treatment with Tizercin.

Hyperglycemia or glucose intolerance has been observed in patients. receiving levomepromazine. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are prescribed treatment with levomepromazine should undergo appropriate glycemic monitoring throughout treatment.

If hyperthermia occurs during treatment with antipsychotic drugs, neuroleptic malignant syndrome (NMS) should be excluded. NMS is a deadly disease characterized by the following symptoms: muscle rigidity, hyperthermia, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, increased sweating), catatonia. Laboratory findings: increased creatine phosphokinase (CPK) levels, myoglobinuria (rhabdomyolysis) and acute renal failure. All these symptoms indicate the development of NMS. If they occur, as well as if hyperthermia of unknown etiology occurs during treatment without pronounced clinical symptoms of NMS, the use of Tizercin should be stopped immediately. If, after recovery from NMS, the patient's condition requires further antipsychotic therapy, the choice of drug should be carefully considered.

Tolerance to the sedative effects of phenothiazines and cross-tolerance to various antipsychotics have been described in the literature. Such tolerance may explain signs of functional impairment that occur after sudden withdrawal of high or long-term doses: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia and restlessness. Therefore, discontinuation of the drug must be done gradually.

Many antipsychotics, including levomepromazine, can lower the epileptic seizure threshold and cause epileptiform electroencephalogram (EEG) changes. Therefore, when gradually adjusting the dose of Tizercin in patients with epilepsy, clinical parameters and EEG should be constantly monitored.

The development of cholestatic jaundice depends on the individual sensitivity of the patient and completely disappears after stopping the drug administration. Therefore, during long-term treatment, regular monitoring of liver function indicators is recommended.

Agranulocytosis and leukopenia have also been observed in some patients treated with phenothiazines. Therefore, during long-term therapy, regular monitoring of the blood count is recommended, despite the very low frequency of these phenomena.

It is prohibited to consume alcoholic beverages during treatment and until the effects of the drug disappear (within 4-5 days after stopping the use of Tizercin).

Blood pressure (especially in patients with an unstable circulatory system and a predisposition to hypotension)

Liver function tests (especially in patients with liver disease)

Blood count (for fever and pharyngitis, as well as for signs of leukopenia and agranulocytosis, at the beginning of treatment and during long-term therapy)

Electrocardiogram (for cardiovascular diseases and in elderly patients).

Potassium level in the blood (periodic monitoring and correction of the level of electrolytes in the blood, especially with long-term, chronic use of the drug).

With the sudden withdrawal of the drug, acute withdrawal symptoms may develop, such as the return of psychotic symptoms, restlessness, increased anxiety symptoms, insomnia, nausea, vomiting, headache, trembling, sweating, increased heart rate.

Since Tizercin 25 mg film-coated tablets contain 40 mg lactose monohydrate per tablet, it should not be administered to patients with hereditary galactose intolerance, Lapp-lactase deficiency, glucose-galactose malabsorption.

Pregnancy and lactation

If antipsychotics (including levomepromazine) were used in the third trimester of pregnancy, then after delivery the newborn is at risk of developing side effects, for example, extrapyramidal symptoms and / or withdrawal symptoms of varying duration and severity. There have been cases with the development of agitation, hypertension, hypotension, tremor, drowsiness, respiratory distress, as well as reports of side effects with malnutrition. Thus, careful monitoring of the condition of newborns should be carried out.

The drug should not be used during pregnancy unless a careful comparison of risk and benefit has been made. Levomepromazine is excreted in breast milk. In this regard, its use during lactation is contraindicated.

Features of the effect of the drug on the ability to drive a vehicle orpotentially dangerous mechanisms

Tizercin may cause drowsiness, disorientation, confusion, or significant hypotension, which may affect the patient's ability to drive. During the treatment period, patients are advised to refrain from driving a vehicle or potentially dangerous machinery. In the future, the degree of restrictions should be set for each patient individually.

Overdose

Symptoms: changes in vital physiological parameters (often arterial hypotension and hyperthermia), conduction disturbances in the heart muscle (prolongation of the QT interval, ventricular tachycardia / fibrillation, pirouette-type tachycardia, atrioventricular block), extrapyramidal symptoms, sedation, excitation of the central nervous system (epileptic seizures) and NNS.

Treatment: monitoring of the following parameters: acid-base balance, water-electrolyte balance, kidney function, urine volume, liver enzymes, electrocardiogram. In patients with NMS, serum CPK and body temperature should be monitored. In accordance with the values ​​of the monitored parameters, symptomatic treatment should be prescribed. With arterial hypotension: intravenous fluids, Trendelenburg position, dopamine and / or norepinephrine (due to the proarrhythmic effect of levomepromazine, it is necessary to have a resuscitation kit ready and monitor the work of the heart).

In case of an overdose of neuroleptics, adrenaline should not be used. Lidocaine (lignocaine) and, if possible, long-acting antiarrhythmic drugs should be avoided. For convulsive conditions, diazepam can be administered, and if seizures resume due to diazepam, phenytoin or phenobarbital can be administered. For rhabdomyolysis, mannitol should be given. A specific antidote is not known. Forced diuresis, hemodialysis and hemoperfusion are not effective. It is not recommended to induce vomiting, as possible epileptic seizures and dystonic reactions of the head and neck can lead to aspiration of vomit. Gastric lavage and monitoring of vital signs should be performed even 12 hours after dosing, since gastric emptying is slowed by the anticholinergic effect of levomepromazine. To further reduce absorption, the introduction of activated charcoal and laxatives is recommended.

Release form and packaging