TIZERCIN

Active material: Levomepromazin
When ATH: N05AA02
CCF: Antipsychotic drug (anxiolytic)
ICD-10 codes (testimony): B02.2, F20, F21, F22, F23, F25, F29, F31, F40, F41.0, F41.2, G50.0, G51
At KFU: 02.01.01.01
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)

Pharmaceutical form, composition and packaging

Pills, coated white, round, slightly biconcave, without smell.

Excipients: magnesium stearate, sodium starch glycolate, povidone, microcrystalline cellulose, potato starch, lactose, Titanium dioxide, gipromelloza, Dimethicone.

50 PC. – vials of dark glass (1) – packs cardboard.

The solution for infusion and the / m colorless or pale green, clear, without smell.

Excipients: sodium bisulfite, vitamin C, water d / and.

1 ml – colorless glass vials (5) – packings Valium planimetric (2) – packs cardboard.

Pharmacological action

Antipsychotic drug (anxiolytic) phenothiazine series. It has antipsychotic, sedation (snotvornoe), analgesic, moderate antiemetic, hypothermic, mild antihistamine and anticholinergic effect of m-. Causes a decrease in blood pressure.

Antipsychotic effect due to blockade of dopamine D₂-receptors and the mesolimbic Mesocortical Systems.

Sedative effect due to blockade of adrenergic receptors of the reticular formation of the brain stem; antiemetic effect – blockade of dopamine D₂-receptor trigger zone of the vomiting center; hypothermic effect – blockade of dopamine receptors of the hypothalamus.

Extrapyramidal side effects are less pronounced at levomepromazina, than “classical” neuroleptics. Levomepromazina increases the pain threshold. With the ability to enhance the analgesic effects of this drug can be used for adjuvant therapy in acute and chronic pain syndrome.

Maximum analgesic effect develops within 20-40 minutes after i / m administration and lasts approximately 4 no.

Pharmacokinetics

Absorption

After oral administration, C_max plasma levels achieved after 1-3 no.

After the / m of C_max plasma levels achieved after 30-90 m.

Distribution

It penetrates the blood-tissue barriers, including GEB, distributed in organs and tissues.

Metabolism

Levomepromazina rapidly metabolized in the liver by demethylation to form sulfate conjugates and glucuronide, are excreted in the urine. Metabolite, resulting from demethylation (N-desmethylomono-methotrimeprazine), possess pharmacological activity, remaining inactive metabolites.

Deduction

T_1/2 is 15-30 no.

A small portion of the administered dose (1%) It appears unchanged in the urine and feces.

Testimony

- Psychomotor agitation of various etiologies: schizophrenia (acute and chronic), in bipolar disorders, in psychosis (including senile and intoxication), in oligophrenia, epilepsy;

- Other mental disorders, proceeding with agitation, anxiously, panic, phobias, sleeplessness;

- Strengthening of analgesics, funds for general anesthesia, antihistamines;

- Pain (neuralgia nerve troynichnogo, neuritis of the facial nerve, shingles).

Dosage regimen

Inside appointed, starting dose 25-50 mg / day in divided doses (of the maximum daily dose should be administered at bedtime), daily increasing it on 25-50 mg to improve the patient's condition. In other neuroleptic-resistant patients the daily dose can be increased faster, raising it to 50-75 mg / day. Average daily doses up 200-300 mg.

Upon improvement of a patient the dose should be reduced to a maintenance, the value of which is determined individually.

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

Parenteral the drug is administered in the absence of the possibility of its ingestion. The daily dose is 75-100 mg, razdelennaya of 2-3 injection, bed rest under the control of blood pressure and heart rate. If necessary, the daily dose was increased to 200-250 mg.

Enter / m (deep) or / drip.

For administration as an I / drip infusion Tisercinum^® (50-100 mg) Dilute in 250 ml isotonic saline or glucose solution (dextrose) and administered slowly through a dropper.

Patients with psychosis, in severe psychomotor agitation it is advisable to begin therapy with parenteral administration levomepromazina.

To prevent the development of orthostatic collapse during treatment required to comply with bed rest.

Side effect

Cardio-vascular system: common – decrease in blood pressure, orthostatic hypotension; possible – tachycardia, Adams' disease, QT prolongation (arrhythmogenic effect, tachycardia type “pirouette”). When receiving neuroleptics phenothiazine series were cases of sudden death (possibly caused by cardiac causes).

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

CNS: drowsiness, dizziness, fatigue, confusion, slurred speech, extrapyramidal symptoms with prevalence Akinetes-hypotonic syndrome, seizures, intracranial hypertension, neuroleptic malignant syndrome (NMS).

On the part of the endocrine system: galactorrhea, menstrual irregularities, mastalgïya, weight loss. With prolonged use described cases of pituitary adenomas, but to establish a causal link its development with phenothiazine derivatives more research is needed.

From the urinary system: discoloration of urine, voiding.

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

Dermatological reactions: photosensitivity, эritema, pigmentation.

On the part of the organ of vision: long-term use of any deposits in the lens and cornea, pigmentnaya retinopathy.

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

Other: hyperthermia (It may be the first sign of NSA), pain and swelling at the injection site.

Contraindications

- Concomitant use of antihypertensive drugs;

- An overdose of funds, providing a depressing effect on the central nervous system (alcohol, general anesthetics, hypnotics);

- Zakrыtougolynaya glaucoma;

- Urinary retention;

- Parkinson's disease;

- Multiple sclerosis;

- Myasthenia;

- Hemiplegia;

- Chronic heart failure decompensation;

- Severe renal insufficiency;

- Severe hepatic impairment;

- Severe hypotension;

- Inhibition of bone marrow hematopoiesis (granulocytopenia);

- Porphyria;

- Lactation;

- Children up to age 12 years;

- Hypersensitivity to other phenothiazines and levomepromazina.

FROM caution used for epilepsy, in patients with cardiovascular disease in history, especially in the elderly (conduction disorder of the heart muscle, Arrhythmia, syndrome, congenital long QT).

Pregnancy and lactation

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

Adequate and well-controlled clinical studies on the safety of Tisercinum^® lactation has not been. Levomepromazina excreted in breast milk. Given these facts, use of the drug while breastfeeding is contraindicated. If necessary, use during lactation should decide the issue of termination of breastfeeding.

Cautions

Use of the drug should be discontinued in the event of allergic reactions.

Extreme care is required during concomitant use with means, CNS depressants, MAO inhibitors and drugs, having anticholinergic activity.

Special care should be prescribed to patients with renal and / or hepatic insufficiency because of the risk of drug accumulation.

Elderly patients have a predisposition to orthostatic hypotension, and to the development of anticholinergic and sedative effects of phenothiazines. Besides, they often occur particularly extrapyramidal side effects. Therefore, in these patients is particularly important to use the drug in low initial doses and gradual increase in their.

To prevent the development of orthostatic hypotension after administration of the first dose the patient must lie within 30 m. If after drug administration occurs dizziness, must comply with bed rest after each dose.

For parenteral administration should be possible to change the injection site, because the drug may have a local irritating effect and tissue damage.

If during antipsychotic treatment there hyperthermia, Be sure to exclude the development of NSAs. NMS – deadly disease, characterized by the following symptoms: hyperthermia, muscle rigidity, confusion, dysfunction of the autonomic nervous system (unstable blood pressure, tachycardia, arrhythmia, desudation), increase in CK, mioglobinuriâ (raʙdomioliz) and acute renal failure. If you experience these symptoms, and if during the treatment of pyrexia of unknown etiology occur without the other clinical symptoms of NMS, introduction Tisercinum^® should cease immediately.

After the sudden withdrawal of the drug, used in high doses or prolonged, may cause 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, the abolition of the drug should always be done gradually.

Many antipsychotics, incl. levomepromazin, may lower the seizure threshold and cause epileptiform EEG changes. Therefore, the selection of dose Tisercinum^® epileptic patients should be continuously monitored clinical parameters and EEG.

The development of cholestatic jaundice depends on the patient's individual sensitivity and disappears completely after the cessation of drug administration. Therefore, long-term treatment requires regular monitoring of liver function.

When long-term therapy is recommended regular monitoring of peripheral blood.

During treatment, avoid alcohol before the disappearance of the effects of the drug (during 4-5 days after discontinuation of Tisercinum^®).

Monitoring of laboratory parameters

Before and during treatment should regularly monitor blood pressure, liver function tests (especially in patients with liver diseases), conduct analyzes of peripheral blood, ECG (cardiovascular diseases and in elderly patients).

Effects on ability to drive vehicles and management mechanisms

During the period of treatment should refrain from driving and performance, associated with an increased risk of accidents.

Overdose

Symptoms: hypotension, conduction abnormalities in heart muscle (QT prolongation, type of ventricular tachycardia “pirouette”, AV блокада), depression of consciousness of varying severity (up to coma), extrapyramidal symptoms, sedation, seizures.

Treatment: resuscitation, simptomaticheskaya therapy. Spetsificheskiy no known antidote. Forced diuresis, hemodialysis and hemoperfusion are not effective.

Drug Interactions

Avoid the simultaneous application Tisercinum^® with antihypertensive agents because of the risk of significant decrease in blood pressure; MAO inhibitors, tk. may increase the duration of effect Tisercinum^® and the severity of the side effects.

It should be used with caution Tisercinum^® in combination with drugs, having anticholinergic activity (tricyclic antidepressants; histamine H₁-receptors, Some antiparkinsonian agents; atropyn, scopolamine, succinylcholine) due to increased anticholinergic effects (paralytic ileus, urinary retention, glaucoma), in combination with scopolamine extrapyramidal side effects; with means, CNS depressants (opioid analgesics, funds for general anesthesia, anxiolytics, sedatives and opiates, tricyclic antidepressants), tk. is enhanced inhibitory action Tisercinum^® CNS; with means, It has a stimulating effect on the central nervous system (incl. amphetamine derivatives), tk. a decrease in the effect of psychostimulant; with levodopa, tk. there is a weakening effect of levodopa; with oral hypoglycemic agents, tk. reduced their effectiveness and dosage adjustment is required; with means, prolonging the QT interval (certain antiarrhythmics, macrolide antibiotics, azole antifungals, cisapride, some antidepressants, Some antihistamines, and diuretics, reduce the level of potassium), tk. increases the risk of QT prolongation and, Consequently, arrhythmias; with means, cause photosensitivity, because of the risk of its strengthening; ethanol, tk. is enhanced inhibitory effect on the central nervous system and increases the likelihood of extrapyramidal side effects.

Tizerцin^® should be used inside for 1 hours before or after 4 hours after ingestion of antacids, tk. while the use of antacids reduces absorption from the gastrointestinal tract levomepromazina.

In an application with Tisercinum^® preparations, suppress bone marrow hemopoiesis, It increases the risk of developing myelosuppression.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug belongs to the list of potent substances №1 Standing Committee on Drug Control MoH.

Drug in tablet form, coated, It should be stored out of reach of children, at a temperature from 15 ° to 25 ° C. Shelf life – 5 years.

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