Instructions for use Tizercin film-coated tablets 25 mg bottle No. 50
Composition
active ingredient: levomepromazine maleate;
1 tablet contains levomepromazine maleate 33.80 mg, corresponding to levomepromazine 25.00 mg;
Excipients: magnesium stearate, sodium starch glycolate (type A), povidone, microcrystalline cellulose, potato starch, lactose monohydrate, hypromellose, titanium dioxide (E 171), dimethicone.
Dosage form
Film-coated tablets.
Main physicochemical properties: round biconvex tablets, film-coated, white, odorless.
Pharmacotherapeutic group
Antipsychotics. Levomepromazine.
ATX code N05A A02.
Pharmacological properties
Pharmacodynamics
Tizercin® is a phenothiazine neuroleptic. Levomepromazine is an analogue of chlorpromazine with a more pronounced inhibitory effect on psychomotor activity.
By blocking dopamine receptors in the thalamus, hypothalamus, reticular and limbic systems, levomepromazine suppresses the sensory system, reduces motor activity and exhibits a pronounced sedative effect; in addition, it has an antagonistic effect on other neurotransmitter systems (noradrenaline, serotonin, histamine, acetylcholine). Due to these properties, levomepromazine has antiemetic, antihistamine, antiadrenergic and anticholinergic effects. Extrapyramidal side effects are less pronounced than with the use of potent neuroleptics. Levomepromazine is a potent antagonist of alpha-adrenergic receptors, but its anticholinergic effect is insignificant. Levomepromazine increases the pain threshold (analgesic activity is similar to morphine) and exhibits amnestic effects. Due to its ability to potentiate the effect of analgesics, levomepromazine can be used as an adjuvant for intense chronic and acute pain.
Pharmacokinetics
After oral administration, it is rapidly absorbed from the gastrointestinal tract. The maximum plasma concentration is reached 1–3 hours after internal administration. Levomepromazine is intensively metabolized with the formation of sulfate and glucuronide conjugates, which are excreted by the kidneys. A small amount of the dose (1%) is excreted in the urine and feces unchanged. The half-life is 15–30 hours.
Indication
Acute psychotic states accompanied by psychomotor agitation and severe anxiety:
acute attacks of schizophrenia; other severe mental conditions.
Adjuvant therapy for chronic psychoses:
chronic schizophrenia; chronic hallucinatory psychoses.
Contraindication
Hypersensitivity to the active substance, phenothiazines or to any other component of the drug; concomitant treatment with other antihypertensive agents; concomitant use with monoamine oxidase inhibitors (MAO); concomitant use with central nervous system (CNS) depressants (alcohol, general anesthetics, hypnotics); angle-closure glaucoma; urinary retention; Parkinson's disease; multiple sclerosis; asthenic bulbar paralysis (myasthenia gravis), hemiplegia; severe cardiomyopathy (circulatory failure); severe renal or hepatic failure; clinically significant hypotension; diseases of the blood-forming organs; porphyria; pregnancy (I trimester) and breastfeeding; children under 12 years of age.
Interaction with other medicinal products and other types of interactions
It is forbidden to use Tizercin® simultaneously with:
antihypertensive drugs - due to an increased risk of developing severe arterial hypotension; MAO inhibitors, as the side effects of Tizercin® may be prolonged and intensified.
Caution should be exercised when using Tizercin® together with anticholinergic agents (tricyclic antidepressants, H1-antihistamines, some antiparkinsonian agents, atropine, scopolamine, succinylcholine), as the anticholinergic effect may be enhanced (paralytic ileus, urinary retention, glaucoma). Extrapyramidal side effects have been observed when used with scopolamine.
There is an increased risk of arrhythmias when neuroleptics are used with tetracyclic antidepressants (e.g. maprotiline).
With simultaneous use of the drug with tri/tetracyclic antidepressants, prolongation and enhancement of sedative and anticholinergic effects are possible, as well as an increased risk of developing neuroleptic malignant syndrome.
When Tizercin is used together with central nervous system depressants (narcotics, general anesthetics, anxiolytics, sedative-hypnotics, tranquilizers, tricyclic antidepressants, neuroleptics), the effect on the central nervous system is enhanced.
Tizercin® weakens the effect of central nervous system stimulants (e.g., amphetamine derivatives) when used simultaneously.
Under the influence of Tizercin®, the antiparkinsonian effect of levodopa is sharply reduced due to the antagonistic interaction caused by the blockade of dopaminergic receptors caused by neuroleptics.
Concomitant use of Tizercin® with drugs that prolong the QT interval (some class IA and III antiarrhythmics, macrolide antibiotics, some azole antifungals, cisapride, some antidepressants, antihistamines, diuretics with hypokalemic action) may cause an additive effect and increase the incidence of arrhythmias.
When Tizercin® and dilevalol are used together, the effects of both drugs are enhanced due to mutual inhibition of metabolism. In the case of simultaneous administration of these drugs, the dose of one or both drugs should be reduced. Such an interaction cannot be excluded when using other beta-blockers.
Photosensitivity may increase when drugs with photosensitizing effects are used simultaneously with Tizercin®.
You should not drink alcohol or use medications containing alcohol during treatment with Tizercin®. Alcohol may increase the depressant effect on the central nervous system, which increases the likelihood of developing extrapyramidal side effects.
When used together with vitamin C, avitaminosis associated with taking Tizercin® is reduced.
Application features
If any type of allergic reaction occurs, the use of the drug should be discontinued immediately.
Tizercin® should be used with extreme caution in combination with anticholinergic agents.
Prescribing the drug to patients with hepatic and/or renal insufficiency requires special attention due to the risk of drug cumulation.
Elderly patients (especially those with dementia) are more likely to develop postural hypotension and are more sensitive to the anticholinergic and sedative effects of phenothiazines. They are also more likely to develop extrapyramidal side effects. It is therefore important to start treatment in such patients at low doses and increase them gradually.
When using Tizercin® in patients at increased risk of stroke, the benefit/risk ratio should be carefully weighed.
Increased mortality in elderly patients with dementia
Two large observational studies have shown that elderly patients with dementia treated with antipsychotics have an increased mortality rate compared with those not treated with these antipsychotics. However, the available data do not allow a reliable assessment of the extent of the risk and the causes of the increased mortality.
Tizercin® is not indicated for the treatment of behavioral disorders caused by dementia.
To avoid postural hypotension, the patient should lie down for 30 minutes after taking the first dose. If dizziness occurs after taking the drug, the patient is advised to remain in bed after each dose.
1 film-coated tablet contains 40 mg lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Caution should be exercised when administering the drug to patients with a history of cardiovascular disease, especially the elderly and patients with congestive heart failure, conduction disorders, arrhythmia, congenital long QT syndrome or unstable circulation. An ECG should be performed before starting treatment with Tizercin®.
Patients with risk factors for arrhythmia should be prescribed Tizercin® with great caution. If the clinical situation allows, before using the drug, it is necessary to ensure that the following risk factors for arrhythmia are absent: bradycardia or atrioventricular block of the 2nd-3rd degree, metabolic disorders such as hypokalemia, hypocalcemia or hypomagnesemia, fasting or alcohol abuse, history of prolonged QT interval, ventricular arrhythmia or torsades de pointes, family history of prolonged QT interval, concomitant use of neuroleptics, concomitant use of other drugs that can provoke bradycardia, electrolyte imbalance, decreased intraventricular conductivity or prolonged QT interval.
Risk of developing venous thromboembolism (VTE)
As with other neuroleptics, neuroleptic malignant syndrome (fatal complications are not excluded), characterized by hyperthermia, muscle rigidity, confusion, impaired autonomic nervous system function (unstable blood pressure, tachycardia, arrhythmias, increased sweating), catatonia and autonomic dysfunction, may occur. Laboratory results: increased levels of creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. All these symptoms indicate the development of NMS, therefore, treatment with Tizercin® should be discontinued immediately if such symptoms appear. Treatment should also be discontinued in the absence of clinical symptoms of NMS, if hyperthermia of unexplained etiology is observed during treatment with Tizercin®. If, after recovery, the patient's condition requires further treatment with antipsychotics, the choice of treatment requires a complete review.
Tolerance to the sedative effects of phenothiazines and cross-tolerance among antipsychotics have been reported. This tolerance may be explained by dysfunctional symptoms that develop after abrupt withdrawal of large doses or after prolonged use: nausea, vomiting, headache, tremor, increased sweating, tachycardia, insomnia, restlessness. Given this phenomenon, the drug should always be withdrawn gradually.
Many neuroleptic drugs, including Tizercin®, can lower the seizure threshold and cause EEG changes. Therefore, in patients with epilepsy, clinical and EEG monitoring should be mandatory during dose titration.
Cholestatic (jaundice-like) hepatotoxic reactions caused by chlorpromazine may also occur with other phenothiazines. This depends on the individual sensitivity of the patient. The reaction disappears completely after discontinuation of treatment. Therefore, liver function should be monitored regularly during long-term treatment.
Hyperglycemia, agranulocytosis and leukopenia have been observed in some patients treated with phenothiazines, therefore, despite the very low frequency of these events, regular monitoring of the blood picture is recommended during long-term treatment with Tizercin®.
During treatment with Tizercin®, as well as for 4–5 days after its discontinuation, the consumption of alcoholic beverages is prohibited.
Before starting treatment and throughout the entire period of therapy, regular monitoring of the following parameters is recommended:
blood pressure (especially in patients with unstable blood circulation and those prone to arterial hypotension); liver function (especially in patients with liver disease); blood test (in case of fever, pharyngitis or suspected leukopenia or agranulocytosis); ECG (in case of cardiovascular diseases and in elderly patients); blood calcium, magnesium and potassium levels.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, you should refrain from driving vehicles and performing work that requires increased attention and speed of psychomotor reactions.
Use during pregnancy or breastfeeding
Pregnancy
In some cases, congenital malformations have been observed in children whose mothers used phenothiazines during pregnancy, but a causal relationship with phenothiazines has not been established.
Due to the lack of data from controlled clinical studies, the drug should not be used during the third trimester of pregnancy.
Breast-feeding
Levomepromazine passes into breast milk, so its use during breastfeeding is contraindicated.
Fertility
There are no data on fertility in animals.
In humans, through interaction with dopamine receptors, levomepromazine can cause hyperprolactinemia, which may be associated with impaired fertility in women.
Method of administration and doses
Adults
Treatment should be started with low doses, which should then be gradually increased, depending on tolerability. After a noticeable improvement in the condition, the dose can be reduced to a maintenance dose, which is set individually by the doctor. The initial dose of the drug is 25–50 mg (1 tablet 1–2 times a day). If necessary, the initial dose can be increased to 150–250 mg (6–10 tablets) in 2–3 doses per day, the maximum part of the daily dose should be taken before bedtime, then, after the condition improves, the dose can be reduced to a maintenance dose. The maximum daily dose is 250 mg. The duration of treatment is set individually by the doctor and depends on the effect of the treatment.
Children (over 12 years old)
Children are sensitive to the hypotensive and sedative effects of levomepromazine, so the recommended daily dose for them is 25 mg.
Elderly patients
The drug is not recommended for patients over 65 years of age, as such people are more sensitive to phenothiazine.
Children
The drug should not be used in children under 12 years of age.
Overdose
Changes in the main indicators of the body's condition (arterial hypotension, hyperthermia), cardiac conduction disorders (prolongation of the QT interval, ventricular tachycardia/ventricular fibrillation, ventricular tachycardia (torsades de pointes), atrioventricular block), extrapyramidal symptoms, sedative effect, excitation of the central nervous system (epileptic seizures) and neuroleptic syndrome, loss of consciousness, tachycardia, changes in the ECG, hypothermia, dyskinesia.
Treatment
Symptomatic treatment should be prescribed according to the results of monitoring the main parameters. In case of arterial hypotension - intravenous fluid administration, Trendelenburg position, dopamine and/or norepinephrine can be used (a resuscitation kit should be available; when using dopamine and/or norepinephrine, cardiac activity should be monitored using an ECG). Convulsions can be eliminated by using diazepam or, if seizures recur, by using phenytoin or phenobarbitone. Mannitol should be prescribed only in the event of rhabdomyolysis.
Forced diuresis, hemodialysis and hemoperfusion are ineffective. Inducing vomiting is not recommended, since aspiration of vomitus may occur during transient epileptic seizures due to spastic movements of the head and neck. Gastric lavage and monitoring of vital signs can be performed even 12 hours after taking the drug, since gastric emptying is slowed down due to the anticholinergic effect of Tizercin®. To reduce the absorption of the drug, it is additionally recommended to take activated charcoal and a laxative.
Treatment of neuroleptic malignant syndrome includes immediate discontinuation of neuroleptics, cold therapy, and possibly dantrolene sodium.
Neuroleptics should be used with caution if their continued use is necessary.
Adverse reactions
Cardiovascular system: the most serious side effect of the drug, which occurs most often, is postural hypotension, accompanied by weakness, dizziness or fainting. Tachycardia, Adams-Stokes syndrome, prolongation of the QT interval (proarrhythmic effect, torsades de pointes arrhythmia) may also be observed; neuroleptic malignant syndrome; heart attacks, which can lead to sudden death.
From the side of the hematopoietic system: pancytopenia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia; venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis; hyperglycemia, withdrawal syndrome in newborns.
Central nervous system: disorientation, confusion, visual hallucinations, slurred speech, extrapyramidal symptoms (dyskinesia, dystonia, parkinsonism, opisthotonus, hyperreflexia), epileptic seizures, increased intracranial pressure, reactivation of psychotic symptoms, catatonia.
Endocrine and metabolic disorders: Galactorrhea, menstrual disorders, weight loss. Pituitary adenoma has been reported in some patients treated with phenothiazines. However, further studies are needed to establish a causal relationship with the drug.
From the genitourinary system: urine discoloration, difficulty urinating, very rarely - chaotic uterine contractions; priapism.
Gastrointestinal: dry mouth, abdominal discomfort, nausea, vomiting, constipation may lead to the development of paralytic ileus, liver damage (jaundice, cholestasis); necrotizing enterocolitis, which can be fatal.
Skin: photosensitivity, erythema, urticaria, pigmentation, exfoliative dermatitis.
On the part of the organs of vision: opacity of the lens and cornea, pigmentary retinopathy.
Hypersensitivity reactions: laryngeal edema, peripheral edema, anaphylactoid reactions, asthma.
Others: hyperthermia, cardiac arrhythmia, glucose intolerance, vitamin deficiency, heat stroke in hot and humid rooms.
Expiration date
5 years.
Do not use the medicine after the expiry date stated on the packaging.
Storage conditions
Store in the original packaging at a temperature not exceeding 25°C, out of the reach of children.
Packaging
50 film-coated tablets in a glass bottle, in a cardboard box.
Vacation category
According to the recipe.
Producer
CJSC Pharmaceutical Plant EGIS, Hungary.
Location of the manufacturer and its business address
EGIS Pharmaceuticals PLC, 9900 Kormend, Matyas kiraly ut. 65, Hungary.
