Tizercin

Tizercin is a neuroleptic of the phenothiazine subgroup. The element levomepromazine is an analogue of chlorpromazine, demonstrating a more powerful suppressive effect on psychomotor activity.

Levomepromazine is a strong α-adrenergic receptor antagonist, which has a weak anticholinergic effect. The active component increases the pain threshold (its analgesic effect is similar to morphine) and has amnestic properties. The ability to potentiate the activity of analgesics allows levomepromazine to be used as an adjuvant drug for severe acute or chronic pain. [ 1 ]

Indications Tizercin

It is used in cases of active forms of psychotic conditions, during which severe anxiety and psychomotor agitation are observed (acute schizophrenic attacks and other severe mental disorders).

Prescribed for adjuvant treatment of chronic psychoses ( schizophrenia and hallucinatory psychoses).

Release form

The drug is released in the form of tablets - 50 pieces in a glass bottle.

Pharmacodynamics

Levomepromazine blocks dopamine endings inside the hypothalamus with the thalamus, as well as the limbic and reticular systems, which leads to the suppression of the sensory system, weakening of motor activity and the development of a powerful sedative effect. Along with this, the drug demonstrates an antagonistic effect in relation to other neurotransmitter systems (serotonin with norepinephrine, acetylcholine and histamine). The result of this activity is the development of antiadrenergic, antihistamine and anticholinergic effects.

Extrapyramidal adverse effects are less severe than in the case of using powerful neuroleptics. [ 2 ]

Pharmacokinetics

When administered orally, the drug is absorbed at high speed in the gastrointestinal tract. Plasma Cmax values are reached after 1-3 hours from the moment of administration.

The substance is involved in intensive metabolic processes with the formation of sulfates and conjugates together with glucuronic acid; these elements are excreted through the kidneys. [ 3 ]

A small portion (1%) is excreted unchanged in feces and urine. The half-life is 15-30 hours.

Dosing and administration

Adults.

Therapy should be started with a small dosage, gradually increasing it (taking into account tolerance). When a noticeable improvement in the patient's condition occurs, the dose is reduced to a maintenance dose (it is selected personally by the doctor).

The initial dose is 25-50 mg (1 tablet 1-2 times a day). If necessary, the initial dosage can be increased to 0.15-0.25 g (6-10 tablets 2-3 times a day). In this case, the maximum part of the daily dose should be consumed in the evening. When the condition improves, the dose is reduced to a maintenance dose. A maximum of 0.25 g of Tizercin can be taken per day.

The duration of therapy is individually selected by the doctor, taking into account the effect of the drug.

For children aged 12 years and over.

Since children are more sensitive to the sedative and antihypertensive effects of levomepromazine, they can be prescribed no more than 25 mg of the drug per day.

• Application for children

The medication cannot be prescribed in pediatrics (children under 12 years of age).

Use Tizercin during pregnancy

In isolated cases, when phenothiazine was used during pregnancy, congenital anomalies in the child were observed, but it was not possible to establish a connection with the use of phenothiazine. Since clinical testing of the drug has not been performed, it is not prescribed in the 3rd trimester.

Levomepromazine is secreted in breast milk, which is why it is not used during breastfeeding.

Contraindications

Main contraindications:

• severe intolerance associated with the active ingredient, phenothiazines or other elements of the drug;
• glaucoma;
• combined use with other antihypertensive substances;
• combination with MAOIs;
• administration together with CNS depressants (general anesthetic drugs, alcohol and sleeping pills);
• Parkinson's disease;
• delay in urination;
• multiple sclerosis;
• myasthenia gravis and hemiplegia;
• severe form of cardiomyopathy (circulatory failure);
• severe liver/kidney failure;
• clinically significant decrease in blood pressure;
• diseases affecting the hematopoietic organs;
• porphyria;
• elderly people (over 65 years of age).

Side effects Tizercin

Side effects include:

• Disorders of the cardiovascular system: orthostatic collapse is often observed, which is accompanied by dizziness, weakness or fainting. In addition, Adams-Stokes syndrome, NMS or tachycardia may develop, as well as prolongation of the QT interval (proarrhythmogenic effect, pirouette-type arrhythmia) and heart attacks, which can cause sudden death;
• problems with the hematopoietic system: leukopenia, thrombocyto- or pancytopenia, agranulocytosis, venous thromboembolism (this includes pulmonary embolism and DVT), hyperglycemia and withdrawal syndrome observed in newborns;
• disorders of the nervous system function: confusion, catatonia, disorientation, epileptic seizures, visual hallucinations, increased intracranial pressure, slurred speech, reactivation of psychotic manifestations and extrapyramidal disorders (dystonia, dyskinesia, opisthotonus, parkinsonism, and hyperreflexia);
• Metabolic and endocrine disorders: menstrual cycle disorders, galactorrhea, and weight loss. Pituitary adenoma has been reported in some individuals using phenothiazine. However, a more detailed study is needed to establish a link with the drug;
• urogenital dysfunction: problems with urination, discoloration of urine and priapism. Chaotic uterine contractions are observed sporadically;
• gastrointestinal disorders: abdominal discomfort, vomiting, xerostomia, nausea and constipation, which can cause paralytic intestinal obstruction. In addition, liver damage (cholestasis or jaundice) and necrotizing enterocolitis, which can lead to death;
• epidermal lesions: erythema, pigmentation, photosensitivity, exfoliative dermatitis and urticaria;
• problems with visual function: clouding of the cornea and lens, as well as pigment retinopathy;
• symptoms of intolerance: peripheral edema, asthma, swelling in the larynx and anaphylactoid manifestations;
• Others: cardiac arrhythmia, hyperthermia, vitamin deficiency, glucose intolerance and development of heat stroke when in a hot, humid room.

Overdose

Signs of poisoning include:

• changes in vital functions (hyperthermia, decreased blood pressure);
• cardiac conduction disorders (pirouette-type tachycardia, prolongation of the QT index, ventricular fibrillation or tachycardia and block);
• extrapyramidal manifestations;
• sedative effect;
• excitation of central nervous system activity (epilepsy attacks) and neuroleptic syndrome;
• changes in ECG readings, loss of consciousness, dyskinesia and hypothermia.

Symptomatic procedures are prescribed taking into account the data from monitoring the main vital functions.

If blood pressure drops, it is necessary to administer fluid, place the patient in the Trendelenburg position, and also use norepinephrine or dopamine (the doctor should have a resuscitation kit with him; when administering norepinephrine or dopamine, it is necessary to monitor the heart function via ECG).

For seizures, diazepam is used; if they recur, phenobarbital or phenytoin is administered.

Mannitol is used only in cases of rhabdomyolysis.

Hemodialysis, forced diuresis and hemoperfusion procedures do not have the desired effect. Vomiting should not be induced, since aspiration of vomit may occur during transient epileptic seizures (due to spastic movements of the neck and head).

Gastric lavage and monitoring of vital functions is allowed even after 12 hours from the moment of drug administration, because the anticholinergic effect of Tizercin inhibits the process of gastric emptying. To reduce the absorption of the drug, a laxative and activated carbon are additionally taken.

In case of NMS, it is necessary to immediately stop taking neuroleptics and perform cold therapy. Dantrolene Na may be administered. If subsequent use of neuroleptics is required, they are used very carefully.

Interactions with other drugs

The medication should not be combined with antihypertensive drugs, as this increases the likelihood of a significant decrease in blood pressure.

It is prohibited to administer the drug together with MAOIs, because this will potentiate and prolong the negative effects of Tizercin.

It is necessary to combine the drug with anticholinergic substances (atropine, tricyclics, H1-antihistamines, succinylcholine, certain antiparkinsonian drugs and scopolamine) with extreme caution - due to the potentiation of the anticholinergic effect (urinary retention, paralytic intestinal obstruction and glaucoma). Administration together with scopolamine causes the development of extrapyramidal disorders.

When using neuroleptics together with tetracyclics (for example, maprotiline), the likelihood of arrhythmias may increase.

Combination with tri- or tetracyclics can also provoke potentiation and prolongation of anticholinergic and sedative effects, as well as an increased likelihood of developing NMS.

Administration together with CNS depressants (general anesthetics, narcotic drugs, tranquilizers, sedative-hypnotics, neuroleptics and tricyclics) potentiates the effect on the CNS.

Tizercin reduces the activity of CNS stimulants (among these are amphetamine derivatives).

The use of the drug greatly weakens the antiparkinsonian effect of levodopa due to the antagonistic interaction that develops due to the blocking of dopaminergic endings by neuroleptics.

Combination of the drug with oral hypoglycemic agents leads to weakening of the latter's effect. This may cause hyperglycemia.

Combination of the drug with drugs that prolong the QT interval (macrolides, certain antiarrhythmic drugs of classes IA and III, cisapride, certain antidepressants, antihistamines, certain azole antimycotics and diuretics with hypokalemic effect) may provoke an additive effect and increase the incidence of arrhythmias.

The use of the drug with dilevalol potentiates the activity of both drugs - this is due to mutual inhibition of metabolic processes. When using these drugs together, the dosage of one of them (or both) must be reduced. Such interaction cannot be ruled out when administering other β-blockers.

When administered with medications that have a photosensitizing effect, photosensitivity may increase.

It is prohibited to consume alcoholic beverages or substances containing alcohol when using Tizercin. Alcohol can potentiate the suppressive effect on the central nervous system and also increases the risk of extrapyramidal disorders.

Combination with vitamin C reduces vitamin deficiency caused by the use of the drug.

Storage conditions

Tizercin should be stored in a place closed to small children. Temperature level – no more than 25°C.

Shelf life

Tizercin can be used within a 5-year period from the date of manufacture of the medicinal product.

Reviews

Tizercin receives mixed reviews from patients who have used it. The drug has a powerful hypnotic and sedative effect, but at the same time, it is noted that there are a large number of side effects and contraindications.