Vitamin E Zentiva® (400 mg). Powerful neuroleptic Chlorprothixene - instructions for use are required to study, reviews of doctors and patients are ambiguous Contraindications to use

It is a fairly strong antipsychotic, has a wide spectrum of action.

The thioxanthene derivative is very effective in helping to overcome both mild and severe disorders mental state, as well as a nervous breakdown and the consequences of alcohol intake.

Pharmacological action of the drug

This is a drug that has antipsychotic, neuroleptic (inhibits the action of the central nervous system), anticonvulsant, antiemetic (antiemetic), tranquilizing (calming) action.

It also tends to enhance the effect of analgesic (pain relieving) drugs.

Has a good thymoleptic influence (antidepressant effect, which is achieved by activating noradrenergic transmission): the speed of thinking, initiative increases, the feeling of fatigue disappears in unusual conditions.

The antipsychotic effect of the drug is associated with its ability to block dopamine receptors, the mesocortical and mesolimbic systems (eliminates delirium, hallucinations).

Chlorprothixene also has the property block adenomine and histamine receptors , which determines its adrenergic blocking and antihistamine action.

The antiemetic property is explained by the ability to inhibit the trigger area of \u200b\u200bthe vomiting center.

Suppresses the release of most hormones of the pituitary gland and hypothalamus.

What happens after taking the medicine

When the drug is taken orally, the active ingredients are absorbed quickly enough. Chlorprothixene begins to act within 20 minutes after consumption, it is quickly absorbed in the intestines.

The maximum concentration in the blood is detected within 2-3 hours after taking the drug.

The elimination half-time from the body is approximately 10-16 hours.

Chlorprothixene has the ability to cross the placenta, is excreted with breast milk in small quantities.

It leaves the body with feces and urine. Accordingly, the organs metabolizing this drug are the kidneys and intestines.

Assuming a daily dose of 300 mg, the content of chlorprothixene in metabolites is 29%, chlorprothixene sulfoxide - 41%.

Indications for use

The drug represents a group of fairly effective sedative antipsychotics and has an extensive group of indications:

Contraindications for admission

Instructions for the use of Chlorprothixene indicate that taking the drug is categorically prohibited:

• a state of alcoholic intoxication or intoxication;
• in case of consumption or overdose of narcotic drugs;
• the action of the central nervous system is inhibited by any other factors;
• increased level of sensitivity to the component (s) of the drug;
• coma;
• severe diseases of the hematopoietic organs;
• bone marrow suppression;
• children under 6;
• vascular collapse (sharp falls blood pressure);
• pregnancy;
• parkinsonism.

Before you decide to take an antipsychotic drug, it must be studied for it - the drug has many side effects.

You can see what the MRI of the brain shows in our video and read about what is happening.

Take with care

The instructions for use indicate that Chlorprothixene tablets also have relative contraindications (taking the drug is possible, but with great care), which are in:

• a combination with other drugs and substances (for more details see "Interaction with other drugs");
• epilepsy clinical stage or at the stage of complications;
• diseases of the renal and hepatic parenchyma;
• decompensated defect;
• somatic exhaustion;
• tachycardia;
• elderly age;
• diseases of the cardiovascular system (possibly a transient increase in blood pressure);
• atherosclerosis of cerebral vessels at a pronounced stage;
• stomach ulcer;
• lesions of the duodenum;
• glaucoma or a predisposition to its occurrence;
• breathing disorders caused by asthma, the course of acute infectious diseases, pulmonary emphysema;
• diabetes;
• benign or malignant growth of the mucous membrane of the prostate gland, which has clinical manifestations (the drug may cause urinary retention).

In case of impaired renal and liver function

The drug should be used with caution, since structural and functional disorders of these organs may occur.

You should be especially careful if you have the following accompanying diseases:

• pheochromocytoma (a hormonally active tumor in the adrenal glands);
• reye's syndrome (taking the drug increases the risk of developing hepatotoxia);
• retention of urine.

Mode of application

General indications for the use of Chlorprothixene Zentiva, which are indicated in instructions:

Take orally by 25-50 milligrams 3-4 times a day. If necessary, it is possible to prescribe 60 grams per day (with a subsequent reduction in dosage), intramuscularly - up to 25-50 milligrams 2-3 times a day.

Usually, the highest dose is taken at bedtime.

Dosage depending on the disease and concomitant condition

Dose size depends largely on the patient's condition:

1. Psychosomatic disorders and severe depressive conditions: Chlorprothixene is used as an auxiliary medicine (as part of complex therapy). Usually, 60 to 90 mg per day is prescribed (the dose is divided into several doses).
2. Psychoses, schizophrenia, manic states: first the drug is taken at 50-200 mg per day, then daily rate increases to 250-300 mg. With advanced conditions of the disease, it is possible to increase the dosage to 1200 milligrams (the daily dose is divided into 3 - 4 doses, about 40% falls in the evening).
3. Supportive therapy: 100-200 milligrams per day.
4. Neuroses: 10-15 mg at bedtime, less often - 30 mg at bedtime, in extreme cases - 45 mg at bedtime.
5. Withdrawal symptoms ("Hangover" or post-drug state): the drug is taken 3 times a day, in a volume of 500 mg (divided into 3 equal portions). In this case, the course lasts 5-7 days. After completing the course, the dose of the drug is reduced to 15-45 milligrams per day (as maintenance therapy, to prevent breakdowns).
6. Irritability, hyperactivity, nervous excitement, confusion in elderly patients: therapy begins with a dosage of 15–90 mg per day, the dose is increased gradually until the appropriate effect is achieved.
7. Insomnia: take 15-30 milligrams of medication an hour before bedtime.
8. Behavioral disorders in children: dosage is calculated according to the formula 0.5-2 mg X child's weight (kg). On average, it is prescribed: for neuroses, 5–30 mg per day, for psychosis, 100–200 mg per day.
9. Pain (to enhance the action of analgesics): take 15–300 mg of the drug per day along with pain relievers.
10. Itchy skin (of various origins): 15-100 milligrams per day, divided into 4 doses.
11. R abortion claim, premature birth: 15 mg in portions (2-3 times a day), for 2-3 days. Then, for 7-10 days, reduced doses of the drug are prescribed.

Injective administration of the drug is prescribed if the patient refuses to take pills or at the beginning of the course (for the fastest possible drug action).

Composition and release forms of the drug

Pills: biconvex, thin film-coated, 15 mg (orange tablets), 50 mg (light brown tablets), available in blisters, in 1 blister of 10 tablets. 1 package contains 50 pieces.

Composition: active ingredient - chlorprothixene hydrochloride.

Auxiliary components: lactose monohydrate, talc, corn starch, calcium stearate, sucrose.

Shell composition: macrogol 6000, 300, talc, aluminum varnish, hypromellose 2910-5.

Injection: ampoules of 1 ml of 2.5% solution, 2 ml of 5% solution. 1 package contains 10 or 100 ampoules.

Drops: for oral administration

Side effects

As an individual reaction of the organism, the following are possible symptoms:

1. Central nervous system: mild extrapyramidal syndrome, inhibition, fatigue, dizziness, drowsiness. In the first 6 hours after taking the drug, akatasia is possible (an irresistible desire to move, inability to sit still). Isolated cases of late dystonia. It is extremely rare that an increase in the level of anxiety is possible, especially in patients with schizophrenia.
2. Digestive system: increased urination, constipation, dry mouth. After prolonged use of the drug, cholestatic jaundice may occur.
3. The cardiovascular system: flushing of the face, tachycardia (heart palpitations), orthostatic hypotension, changes on the echocardiogram (QT interval).
4. Organs of vision: sometimes patients experience blurred vision, inability to focus quickly.
5. Hematopoietic system: possible leukocytosis, hemolytic anemia, agranulocytosis (4-10 weeks of treatment), benign leukopenia.
6. Endocrine system: possible amanorrhea, frequent hot flashes, galactorrhea, gynecomastia, weakening of sexual desire and potency (with prolonged use of the drug), diabetes mellitus.
7. Metabolism: sometimes there is an increase in the amount of sweating, an increase in appetite, a violation of carbohydrate metabolism, accompanied by weight gain (with prolonged use of the drug).
8. Epidermis: possible photodermatitis or photosensitization.
9. Vestibular apparatus: in some cases, a violation of the coordination of movements (trembling, slowness) is possible.

Drug overdose

Symptoms: respiratory failure, convulsions, severe drowsiness, fever, tachycardia, decreased blood pressure, shock, coma, uncontrolled movements, excessive excitability.

Treatment: you can wash the stomach, give laxatives or absorbents. Also, supportive therapy should be carried out in parallel, depending on the symptoms manifested.

Dialysis will not be effective.

In case of cardiovascular symptoms, do not give adrenaline (this can cause a drop in blood pressure).

Convulsions can be treated with diazepam.

Bioperiden effectively helps in the case of motor neuropathic disorders.

Do not try to induce vomiting, as it is possible for particles of vomit to enter the respiratory tract.

special instructions

Instructions for use for the drug Chlorprothixene Zentiva indicates that one should also remember such moments:

1. Taking Chlorprothixene can give false results immunobiological urine pregnancy test, blood test for bilirubin levels.
2. During the course of treatment, it is advisable not to drink alcohol, to avoid a significant amount of ultraviolet radiation.
3. During intensive treatment, one should refrain from actions that require a high speed of physical and mental reactions (this includes high-altitude work, driving a motor transport, crane ...).
4. In order to avoid the "withdrawal" syndrome (leveling the results of treatment), the drug should be withdrawn from the body gradually, gradually reducing the dosage.
5. The likelihood of BP fluctuations is higher in adolescents than in adults.
6. In the presence of diseases indicated in the list of relative contraindications, the need for treatment with this drug and the possible risks should be carefully compared.
7. Long-term use of the drug is addictive and addictive.

Interaction with other drugs

Interaction of the drug with other drugs is good enough studied:

• using Chlorprothixene in parallel with neuroleptics, hypnotics, anesthetic and sedative drugs, ethenol-containing, they can increase the effect of Chloroprothixene on the central nervous system;
• combination with antihistamines and anticholinergics can lead to a slowdown in the conduction of nerve impulses;
• Chloroprothixene enhances the effect of antihypertensive drugs;
• the combination of a medication with adrenaline can provoke tachycardia, arterial hypotension;
• Chloroprothixene reduces the effectiveness of levodopa;
• the combination of the drug with phenothiazines, haloperidol, reserpine, metoclopramide can cause movement disorders (against the background of neurological complications).

Chlorprothixene belongs to antipsychotics, antipsychotic drugs.

Composition and form of release

The drug is produced in the form of round biconvex tablets, which are film-coated. The tablets contain the active substance - chlorprothixene hydrochloride in the amount of 15 mg or 50 mg.

Additional components include lactose monohydrate, corn starch, talc, sucrose, calcium stearate. Tablets are packed in blisters - 10 pieces each.

An analogue of Chlorprothixene is the drug Truxal.

pharmachologic effect

As a result of the use of Chlorprothixene, the body has an antipsychotic effect, since the drug blocks dopamine receptors. And this, in turn, contributes to the analgesic and antiemetic effects. The instruction for Chlorprothixene explains that this drug, by blocking H1-histamine receptors, 5-HT2 receptors, α1 -adrenergic receptors, has hypotensive, adrenergic blocking and antihistamine effects.

Indications for the use of Chlorprothixene

According to the instructions, Chlorprothixene is effective for:

• violation of behavior in children;
• insomnia;
• psychosis, including manic states and schizophrenia, accompanied by anxiety, psychomotor agitation and agitation;
• with psychosomatic disorders, neuroses, depressive conditions;
• irritability, hyperactivity, confusion, agitation in the elderly;
• for pain (the medicine is used as one of the components of combination therapy);
• with hangover withdrawal syndrome, with alcoholism and drug addiction.

Contraindications

• individual intolerance to one or more substances that make up the drug, or hypersensitivity to them;

• with vascular collapse;
• pheochromocytoma;
• diseases of the hematopoietic organs;
• depression of the central nervous system, the causes of which may be: taking opiates, alcohol and barbiturates;
• if the patient is in a coma.

Method of administration and dosage

In psychosis, schizophrenia, manic states, the drug or an analogue of Chlorprothixene is taken from 50-100 mg per day, then the dosage is gradually increased until it reaches 300 mg per day. Particularly severe cases allow an increase in dosage up to 1200 mg per day. As a rule, the daily dosage is not taken at one time, but divided into three doses. Wherein, most of the dose is taken in the evening, since the drug has a pronounced sedative effect. To perform supporting functions, it is recommended to use the dosage of the drug - from 100 to 200 mg per day.

Hangover withdrawal symptoms are relieved by the use of Chlorprothixene at a dosage of 500 mg, this amount of the drug is divided into two or three doses. Typically, the duration of treatment is one week. After the symptoms of withdrawal symptoms disappear, you can gradually reduce the dosage, bringing it to a maintenance one - from 15 to 45 mg per day. This amount is enough to reduce the possibility of another binge and stabilize general state the patient's body.

Elderly people with hyperactivity, irritability, nervous excitement and confusion are advised to start taking the medicine with a dosage of 15 to 90 mg per day, which must be divided into three doses.

According to the instructions, Chlorprothixene is prescribed to children for the purpose of behavior correction. To calculate the dosage, it is necessary to observe the proportion of 0.5-2 mg of the drug per kg of the child's weight.

Psychosomatic disorders and depressive conditions are treated by using the drug as part of a combination therapy. In this case, dosages of up to 90 mg per day are adhered to. The required amount of the drug must be divided into two or three doses.

Since the analogues of Chlorprothixene, like the drug itself, do not cause addiction and drug dependence, there is a possibility of their use for a long time.

Due to its analgesic properties, Chlorprothixene is used for pain in conjunction with other analgesics. The dosage in this case is 15 - 300 mg per day.

Pregnancy and breastfeeding

Side effects of Chlorprothixene

Judging by the reviews about Chlorprothixene, the use of the drug can provoke the following side effects:

• dysmenorrhea;
• dizziness;
• tachycardia;
• dry mouth;
• difficulty of accommodation;
• rashes on the skin;
• excessive sweating;
• hemolytic anemia;
• transient benign leukopenia;
• constipation;
• drowsiness;
• extrapyramidal symptoms;
• lowering the convulsive threshold.

With long-term use of Chlorprothixene, according to reviews, it is possible to develop orthostatic hypotension, cholestatic jaundice, gynecomastia, galactorrhea. In addition, long-term use of the drug helps to increase body weight, increase appetite, and decrease libido.

Overdose

According to reviews of Chlorprothixene, symptoms of an overdose are: hyper- or hypothermia, extrapyramidal symptoms, convulsions, shock, coma.

In case of an overdose, supportive and symptomatic treatment is carried out.

Interaction with other drugs

Simultaneous use of Chlorprothixene with:

• antipsychotics, anesthetics, sleeping pills, analgesics, sedatives, ethanol-containing and opioid drugs can enhance its effect on the central nervous system;
• with anticholinergic, antihistamines, antiparkinsonian drugs, enhances the anticholinergic effect of Chlorprothixene;
• with antihypertensive drugs increases their effect;
• with adrenaline - the development of arterial hypotension and tachycardia is possible;
• with levodopa reduces medicinal actions last;
• with metoclopramide, haloperidol, reserpine, phenothiazines leads to extrapyramidal disorders.

Storage conditions

Chlorprothixene is stored in a cool, dry place. In this case, its therapeutic properties are retained for no longer than three years.

Description

Coated tablets are brown, round, with a biconvex surface. The cross section shows an almost white core.

Composition

One tablet contains: active substance: chlorprothixene hydrochloride - 15 mg, 25 mg or 50 mg; excipients:corn starch, powdered sugar, talc, calcium stearate, lactose monohydrate, Opadray II (brown) (including partially hydrolyzed polyvinyl alcohol, talc, macrogol 3350, titanium dioxide E 171, iron oxide yellow E 172, iron oxide red E 172, iron oxide black E 172, indigo carmine E 132).

Pharmacotherapeutic group

Antipsychotic drugs. Thioxanthene derivatives.
ATX code:N05AF03.

Pharmacological properties"type \u003d" checkbox "\u003e

Pharmacological properties

Chlorprothixene is an antipsychotic agent of the thioxanthene group.
The antipsychotic effect of these drugs is associated with blockade of dopamine receptors, as well as, possibly, blockade of 5-HT receptors (5-hydroxytryptamine, serotonin). In vivo, chlorprothixene has a high affinity for the D1 and D2 dopamine receptors. Chlorprothixene also has a high affinity for 5-HT2 receptors and α1 -adrenergic receptors, which is similar to high-dose phenothiazines, levomepromazine, chlorpromazine and thioridazine, as well as the atypical antipsychotic clozapine. Chlorprothixene has been shown to have an affinity for histamine (H1) receptors at the diphenhydramine level. In addition, chlorprothixene has an affinity for cholinergic muscarinic receptors. The receptor binding profile of chlorprothixene is very similar to that of clozapine, however, chlorprothixene has about 10 times higher affinity for dopamine receptors.
In all studies with behavioral models for antipsychotic activity (blocking dopamine receptors), chlorprothixene has shown a pronounced antipsychotic effect. A relationship has been demonstrated between the two in vivo models, the in vitro affinity for dopamine D2 receptors and the average daily oral dose of the antipsychotic.
IN clinical application chlorprothixene is a high-dose sedative antipsychotic wide range, which is used to treat psychotic disorders with the exception of depression.
Chlorprothixene reduces the severity or eliminates anxiety, obsessions, psychomotor agitation, anxiety, insomnia, as well as hallucinations, delusions and other psychotic symptoms.
The very low incidence of extrapyramidal effects (about 1%) and tardive dyskinesia (about 0.05%) (according to 11,487 patients) indicate that chlorprothixene can be successfully used for maintenance therapy in patients with psychotic disorders. Low doses of chlorprothixene have an antidepressant effect, which makes useful application this drug with mental disorderscharacterized by anxiety, depression and anxiety. Also, with chlorprothixene therapy, the severity of associated psychosomatic symptoms decreases.
Chlorprothixene is not addictive, addictive, or tolerant. In addition, chlorprothixene potentiates the action of analgesics, has its own analgesic effect, as well as antipruritic and antiemetic properties.
Pharmacokinetics
Suction
The maximum concentration in blood plasma is reached approximately 2 hours (from 0.5 to 6 hours) after oral administration... The average oral bioavailability of chlorprothixene is about 12% (from 5 to 32%).
Distribution
The apparent volume of distribution (Vd) is about 15.5 l / kg. Plasma protein binding - more than 99%.
Chlorprothixene crosses the placental barrier.
Metabolism
Chlorprothixene is predominantly metabolized by sulfoxidation and side chain N-demethylation. Ring hydroxylation and N-oxidation occur to a lesser extent. Chlorprothixene was found in bile, indicating intestinal hepatic recirculation. Metabolites have no antipsychotic activity.
Withdrawal
The half-life (T½) is about 15 hours (from 3 to 29 hours). Average systemic clearance (Cls) is approximately 1.2 L / min. Chlorprothixene is excreted by the kidneys and intestines.
In small amounts excreted in breast milk. The milk / plasma ratio in breastfeeding women ranges from 1.2 to 2.6.
There were no differences in plasma concentrations or elimination rates between the control group and the alcoholic group, regardless of whether the latter were sober or under the influence of alcohol during the study.
Elderly patients (over 65)

Liver dysfunction
The experience of application is insufficient.
Renal dysfunction
The experience of application is insufficient.

Indications for use

Psychotic disorders with the exception of depression.
Contraindications
Increased sensitivity to active substance, other thioxanthenes, or any of the excipients.
Depression of the central nervous system, regardless of the cause (for example, intoxication with alcohol, barbiturates or opiates), vascular collapse, coma.
Chlorprothixene can cause prolongation of the QT interval. Prolonged lengthening of the QT interval may increase the risk of malignant arrhythmias. Therefore, chlorprothixene is contraindicated in patients with a history of clinically significant cardiovascular disease (for example, severe bradycardia (< 50 ударов в минуту)), недавно перенесенным инфарктом миокарда, нелеченной сердечной недостаточностью, гипертрофией сердца, аритмиями, при которых назначают antiarrhythmic drugs IA and III classes), as well as patients with ventricular arrhythmia or pirouette ventricular tachycardia (torsade de pointes).
Chlorprothixene is contraindicated in patients:
- with uncorrected hypokalemia,
- with uncorrected hypomagnesemia,
- with the syndrome of prolongation of the QT interval,
- simultaneously receiving medicineslengthening the QT interval.

Method of administration and dosage

Adults
Psychoses: 50-100 mg / day in divided doses. The dose can be increased up to 600 mg / day.
Maintenance dose: 100-200 mg / day in divided doses.
Children and adolescents
Chlorprothixene is not recommended for use in children and adolescents under 18 years of age due to the lack of sufficient controlled studies.

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Side effects

The most common side effects that can occur in more than 10% of patients are dry mouth, increased salivation, drowsiness and dizziness.
Most of the side effects depend on the dose of the drug used. The incidence of side effects and their severity are most pronounced at the beginning of treatment and decrease as therapy continues. Movement disorders can be observed especially at the beginning of treatment. In most cases, such side effects are eliminated by dose reduction and / or the use of antiparkinsonian drugs. Prophylactic use of antiparkinsonian drugs is not recommended. Antiparkinsonian drugs do not help with tardive dyskinesias, on the contrary, they can worsen symptoms. A dose reduction or, if possible, discontinuation of treatment is recommended. For persistent akathisia, benzodiazepines or propranolol may help.
Information on the incidence of side effects is presented on the basis of literature data and spontaneous reports.
Frequency is listed as: very common (\u003e 1/10); often (\u003e 1/100 and<1/10); нечасто (>1/1000 and<1/100); редко (>1/10000 and<1/1000); очень редко (< 1/10000); либо неизвестно (не может быть оценена на основании существующих данных).
On the part of the blood and lymphatic system: rarely - thrombocytopenia, neutropenia, leukopenia, agranulocytosis.
From the immune system:rarely - hypersensitivity, anaphylactic reactions.
From the endocrine system:rarely - hyperprolactinemia.
From the side of metabolism and nutrition:often - increased appetite, weight gain; infrequently - decreased appetite, weight loss; rarely - hyperglycemia, impaired glucose tolerance.
Mental disorders:often - insomnia, nervousness, agitation, decreased libido.
From the nervous system: very often - drowsiness, dizziness; often - dystonia, headache; infrequently - tardive dyskinesia, parkinsonism, convulsions, akathisia; very rarely - neuroleptic malignant syndrome.
On the part of the organ of vision:often - violation of accommodation, visual impairment; infrequently - gaze cramp.
From the side of the heart:often - tachycardia, palpitations; rarely - lengthening of the QT interval.
From the side of the vessels:infrequently - hypotension, hot flashes; very rarely - venous thromboembolism.
From the respiratory system, chest and mediastinal organs: rarely - shortness of breath.
From the gastrointestinal tract:very often - dry mouth, increased salivation; often - constipation, dyspepsia, nausea; infrequently - vomiting, diarrhea.
From the liver and biliary tract: infrequently - changes in laboratory parameters of liver function; very rarely - jaundice.
On the part of the skin and subcutaneous tissues:often - hyperhidrosis; infrequently - rash, itching, photosensitivity, dermatitis.
From the musculoskeletal system and connective tissue: often - myalgia; infrequently - muscle rigidity.
From the kidneys and urinary tract:infrequently - urination disorder, urinary retention.
Influence on the course of pregnancy, postpartum and perinatal conditions: unknown - withdrawal syndrome in newborns.
On the part of the genitals and mammary gland: infrequently - ejaculation disorders, erectile dysfunction; rarely - gynecomastia, galactorrhea, amenorrhea.
General disorders and disorders at the injection site:often - asthenia, fatigue.
When taking Chlorprothixene, as with other antipsychotics, the following rare side effects were observed: prolongation of the QT interval, ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), pirouette ventricular tachycardia (torsade de pointes) and sudden death.
Cases of priapism, prolonged and usually painful penile erection, possibly leading to erectile dysfunction, have been reported with antipsychotics with an unknown frequency.
Abrupt discontinuation of Chloprothixene can lead to the development of a withdrawal syndrome. The most common symptoms are nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, myalgia, paresthesia, insomnia, nervousness, anxiety, and agitation. Patients may also experience dizziness, abnormal body temperature control, and tremors. Symptoms usually begin within 1-4 days after withdrawal and improve within 1-2 weeks.

Interaction with other medicinal products

Combinations requiring caution when using
Chlorprothixene can enhance the sedative effect of alcohol, the effects of barbiturates and other drugs that depress the central nervous system.
Antipsychotics can increase or decrease the effect of antihypertensive drugs. The antihypertensive effect of guanethidine and similar drugs is reduced.
Concomitant use of antipsychotics and lithium increases the risk of neurotoxicity. Tricyclic antidepressants and antipsychotics mutually inhibit each other's metabolism.
Chlorprothixene can reduce the effectiveness of levodopa and the effect of adrenergic drugs and enhance the effect of anticholinergics.
Concomitant use with metoclopramide and piperazine increases the risk of developing extrapyramidal disorders.
The antihistaminic effect of chlorprothiixene can suppress or eliminate the alcohol / disulfiram reaction.
The prolongation of the QT interval associated with the use of antipsychotics can be exacerbated by the concomitant use of other drugs that prolong the QT interval.
Co-administration with the following drugs that prolong the QT interval is contraindicated:
- antiarrhythmic drugs of class IA and III (for example, quinidine, amiodarone, sotalol),
- some antipsychotic medicines (for example, thioridazine),
- some macrolide antibiotics (for example, erythromycin),
- some antihistamines (for example, terfenadine, astemizole),
- some quinolone antibiotics (for example, moxifloxacin).
This list is incomplete, the simultaneous use of other drugs that can cause a significant lengthening of the QT interval (such as cisapride, lithium) is also contraindicated.
Avoid the simultaneous use of drugs that cause electrolyte disturbances, such as thiazide diuretics, and that can increase the concentration of chlorprothixene in the blood plasma due to a possible increase in the risk of prolongation of the QT interval and the development of malignant arrhythmias.
Antipsychotics are metabolized by the liver cytochrome P450 system.
Medicines that inhibit cytochrome CYP 2D6 (for example, paroxetine, fluoxetine, chloramphenicol, disulfiram, isoniazid, MAO inhibitors, oral contraceptives, to a lesser extent buspirone, sertraline or citalopram) can increase the concentration of chlorprothixene in the blood plasma. The simultaneous administration of chlorprothixene and drugs with anticholinergic action enhances this anticholinergic action.

Precautions

Malignant neuroleptic syndrome
When taking antipsychotics, cases of malignant neuroleptic syndrome with the following symptoms were reported: hyperthermia, muscle rigidity, dysfunction of the autonomic nervous system, impaired consciousness and increased serum creatine kinase. The risk may be higher with a potent drug.
Among the fatal cases, the largest number of patients with the existing organic brain syndrome, mental retardation and abuse of opiates or alcohol.
Treatment: discontinuation of antipsychotics, symptomatic and general supportive inpatient treatment. Symptoms may persist for up to a week after stopping oral antipsychotics.
Due to pupil dilation, patients with a shallow anterior chamber of the eye and angle-closure glaucoma may develop acute glaucoma.
Due to the risk of malignant arrhythmias, Chlorprothixene should be used with caution in patients with a history of cardiovascular disease and in patients with a family history of prolonged QT interval.
Before starting treatment, it is necessary to conduct an ECG study. With a QT interval over 450 msec in men and 470 msec in women, Chlorprothixene is contraindicated.
During therapy, the need for an ECG is assessed by the doctor individually. If the QT interval is prolonged during treatment, it is necessary to prescribe lower doses of Chlorprothixene; if the QT interval is prolonged over 500 msec, therapy should be discontinued.
It is recommended that electrolyte balance be evaluated periodically during treatment.
The simultaneous use of other antipsychotics should be avoided.
Chlorprothixene should be used with caution in patients with organic brain syndrome, seizure disorders, severe liver or kidney dysfunction, severe pseudoparalytic myasthenia gravis and benign prostatic hypertrophy.
Cases of priapism have been reported with the use of antipsychotics with a β-adrenergic blocking effect. The likelihood of this effect in Chloprothixene is not excluded. Severe priapism may require medical attention. Patients should be advised to seek emergency medical attention if signs and symptoms of priapism develop.
Precautions should be taken in patients with:
- pheochromocytoma,
- neoplasia caused by prolactin,
- severe hypotension or orthostatic dysregulation,
- Parkinson's disease,
- diseases of the hematopoietic system,
- hyperthyroidism,
- violation of urination, urinary retention, pyloric stenosis, intestinal obstruction.
Chlorprothixene can change the concentration of insulin and glucose in the blood, therefore, patients with diabetes mellitus may need to adjust the dose of hypoglycemic drugs.
To decide on the possibility of reducing the maintenance dose during long-term therapy, especially with the maximum daily doses, it is necessary to carry out regular monitoring of the patient's condition.
It was reported about the development of venous thromboembolism while taking antipsychotic drugs. Due to the fact that patients treated with antipsychotic drugs are often at risk of developing venous thromboembolism, before and during treatment with chlorprothixene, it is necessary to determine the risk factors for developing venous thromboembolism and take preventive measures.

Use in children and adolescents under 18 years of age

Chlorprothixene is not recommended for use in children and adolescents. Research data on the efficacy and safety of chlorprothixene in children and adolescents is insufficient. Therefore, Chlorprothixene should be prescribed to children and adolescents (up to 18 years of age) only if there is an indication for use and after a careful assessment of the balance of benefits and risks.

Elderly patients

Cerebrovascular Adverse Reactions
In patients at risk of stroke, chlorprothixene should be used with caution.
In randomized, placebo-controlled clinical trials of the use of some atypical antipsychotic drugs in patients with dementia, there was a 3-fold increase in the risk of cerebrovascular adverse reactions... The mechanism for this increased risk is unknown. An increase in risk cannot be excluded when using other antipsychotics in other groups of patients.
Elderly patients are particularly susceptible to orthostatic hypotension.
Increased mortality in elderly patients with dementia. Data from two large observational studies showed that elderly patients with dementia who took antipsychotics had a slightly increased risk of death compared with patients who did not take antipsychotics. There is no sufficient data to accurately assess the magnitude of the risk and the reasons for its increase.
Chlorprothixene is not recommended for the treatment of behavioral disorders in elderly patients with dementia.

Chlorprothixene Zentiva: instructions for use and reviews

Latin name: Chlorprothixen-Zentiva

ATX code: N05AF03

Active substance: chlorprothixene

Manufacturer: Zentiva k.s (Czech Republic, Slovakia), Zentiva Saglik Urunleri Sanayi ve Ticaret A.S. (Turkey), s.c. Zentiva, S.A. (Romania)

Description and photo update: 21.11.2018

Chlorprothixene Zentiva is a drug with an antipsychotic, moderate antidepressant and pronounced sedative effect.

Release form and composition

The dosage form of Chlorprothixene Zentiva is film-coated tablets: round biconvex, orange (15 mg each) or from light brown to light yellow (50 mg each); the color of the core at the break is from almost white to white (in a cardboard box there are 3 or 5 blister packs of 10 pcs.).

Composition of 1 tablet:

• active substance: chlorprothixene hydrochloride - 15 or 50 mg;
• auxiliary components (15/50 mg): corn starch - 10 / 37.5 mg; lactose monohydrate - 92/135 mg; sucrose - 10/20 mg; calcium stearate - 1.5 / 3.75 mg; talc - 1.5 / 3.75 mg;
• shell (15/50 mg): hypromellose 2910/5 - 2.011 / 3.659 4 mg; macrogol 6000 - 0.069 / 0.133 3 mg; macrogol 300 - 0.49 / 0.916 6 mg; talc - 1.43 / 2.419 4 mg; aluminum varnish based on sunset yellow dye (E110) - 1/0 mg; titanium dioxide - 0.342 3 mg.

Pharmacological properties

Pharmacodynamics

Chlorprothixene is a neuroleptic, a thioxanthene derivative. It has antipsychotic, moderate antidepressant and pronounced sedative effects. The antipsychotic effect is associated with the blocking effect of chlorprothixene on dopamine receptors. Also, the analgesic and antiemetic properties of the drug are associated with the blockade of these receptors. Chlorprothixene is able to block a1-adrenergic receptors, 5-HT2 receptors, as well as H1-histamine receptors, which determines its adrenergic blocking hypotensive and antihistaminic action.

Pharmacokinetics

When taken orally, the bioavailability of chlorprothixene is approximately 12%. After oral administration, it is absorbed well and quickly. In the liver and intestinal walls, it undergoes presystemic metabolism. Has the effect of the first passage through the liver.

Chlorprothixene crosses the placental barrier and into breast milk.

Excretion is carried out by the intestines and kidneys: chlorprothixene - 29%, chlorprothixene sulfoxide - 41%.

The half-life is in the range of 8 to 12 hours.

Indications for use

Indications for Chlorprothixene Zentiva are the following conditions and diseases:

• insomnia;
• psychoses, including manic states and schizophrenia, accompanied by psychomotor agitation, anxiety and agitation;
• depressive conditions, neuroses, psychosomatic disorders;
• withdrawal symptoms in alcoholism and drug addiction;
• behavioral disorders in children;
• confusion, hyperactivity, agitation, irritability in elderly patients;
• pain (in combination with analgesics).

Contraindications

Absolute:

• bone marrow suppression;
• pathological changes in the blood;
• pheochromocytoma;
• intolerance to lactose or fructose, glucose-galactose malabsorption or lactase deficiency, isomaltase / sucrase deficiency (Chlorprothixene Zentiva contains lactose and sucrose);
• oppression of the central nervous system of any origin (including those associated with the intake of alcohol, opiates or barbiturates);
• vascular collapse;
• coma;
• age up to 6 years;
• individual intolerance to the components of the drug, including phenothiazines.

Relative (Chlorprothixene Zentiva is prescribed under medical supervision):

• tendency to collapse;
• diabetes;
• glaucoma (including the presence of a predisposition to its occurrence);
• urinary retention and the risk of its development in clinical manifestations of prostatic hyperplasia;
• renal / hepatic impairment;
• reye's syndrome;
• parkinson's disease (associated with increased extrapyramidal disorders);
• severe cardiovascular and respiratory failure associated with acute infectious diseases, asthma or emphysema (there is a high risk of transient increase in blood pressure);
• pronounced atherosclerosis of the vessels of the brain;
• peptic ulcer of the stomach and duodenum;
• epilepsy (associated with the likelihood of increased frequency of seizures as a result of lowering the seizure threshold);
• pregnancy and lactation.

Instructions for the use of Chlorprothixene Zentiva: method and dosage

Chlorprothixene Zentiva is intended for oral administration. It is possible to carry out long-term therapy, since the drug does not cause addiction or drug dependence.

• psychoses, including manic states and schizophrenia: the initial daily dose is 50-100 mg. The dose is gradually increased until the optimal effect is achieved, usually 300 mg. The average maintenance dose is 100 to 200 mg per day. The maximum is 600 mg per day. Usually the daily dose is divided into 2-3 doses, the smaller part should be taken in the daytime, the larger - in the evening;
• withdrawal symptoms for drug addiction and alcoholism: daily dose - 500 mg in 2-3 doses. Duration of use is 7 days. After improvement of the condition, the dose is gradually reduced. The maintenance daily dose ranges from 15 to 45 mg. Taking Chlorprothixene Zentiva allows you to stabilize the condition, reduce the likelihood of developing another binge;
• hyperactivity, irritability, agitation, confusion in elderly patients: 15 to 90 mg daily in 3 divided doses;
• behavior disorder in children: 0.5–2 mg / kg;
• neuroses, depressions, psychosomatic disorders: daily dose - 90 mg in 2-3 doses;
• insomnia: 15-30 mg 60 minutes before bedtime;
• pain (in combination with analgesics): 15-300 mg per day.

Side effects

Possible adverse reactions (\u003e 10% - very common;\u003e 1% and< 10% – часто; > 0.1% and< 1% – нечасто; > 0.01% and< 0,1% – редко; < 0,01% – очень редко):

• cardiovascular system: orthostatic hypotension (especially with high doses of Chlorprothixene Zentiva), transient changes q-T interval on the electrocardiogram and tachycardia;
• nervous system: dizziness, increased fatigue, drowsiness, psychomotor lethargy, mild extrapyramidal hypokinetic-hypertensive syndrome, akathisia (within the first 6 hours after administration), dystonic reactions, persistent tardive dyskinesia (disorders usually appear at the beginning of therapy and often as it continues disappear on their own); rarely - late dystonia, neuroleptic malignant syndrome;
• endocrine system: rarely - dysmenorrhea; at long-term use high doses of Chlorprothixene Zentiva - galactorrhea, diabetes mellitus, gynecomastia, decreased potency / libido, increased sweating, changes in carbohydrate metabolism, increased appetite, weight gain;
• digestive system: xerostomia (is transient); rarely - constipation, cholestatic jaundice (with a prolonged course, especially with the use of high doses, the development of a disorder is most likely between 2 and 4 weeks of therapy);
• hematopoietic organs: rarely - agranulocytosis (the disorder most often develops at 4-10 weeks of treatment); in isolated cases - transient benign leukopenia and hemolytic anemia;
• sensory organs: clouding of the lens / cornea with possible visual impairment, paresis of accommodation (occurs at the beginning of treatment and disappears as you continue to take Chlorprothixene Zentiva);
• others: skin rash, urinary retention, dermatitis, flushing, withdrawal, photosensitivity.

Overdose

The main symptoms: drowsiness, hyper- or hypothermia, convulsions, coma, shock, extrapyramidal symptoms.

In case of overdose, symptomatic and supportive therapy is usually prescribed. As soon as possible, gastric lavage should be performed, taking activated carbon... Also shown are measures aimed at maintaining the work of the cardiovascular and respiratory systems. Epinephrine should not be used because it can cause a subsequent drop in blood pressure. Extrapyramidal disorders can be stopped with biperiden, convulsions with diazepam.

special instructions

Taking the drug can lead to false indicators of hyperbilirubinemia, false positive result when conducting an immunobiological urine test for pregnancy, a change in the QT interval on an electrocardiogram.

Alcohol abuse increases central nervous system depression.

Most often, the development of dystonic reactions is observed in children and young patients. They usually appear at the beginning of therapy and may subside within 24–48 hours after Chlorprothixene Zentiva is discontinued.

In the first few days of treatment, parkinsonian extrapyramidal effects may occur, but usually their frequency increases with increasing dose; more often they occur in elderly patients and older children

Tardive dyskinesia at the beginning of treatment is dose-dependent, but its frequency may increase with a prolonged course and as the total dose is reached. After the cancellation of Chlorprothixene Zentiva, the violation may persist.

The risk of developing extrapyramidal and hypotensive reactions in adolescents is higher than in adult patients.

During the use of Chlorprothixene Zentiva, a blood test and determination of leukocyte formula, monitoring of indicators of hepatic function, conducting an ophthalmological examination, as well as careful observation to identify early signs late dystonia and dyskinesia.

The onset of neuroleptic malignant syndrome is possible at any time of therapy, but more often its development is noted soon after the start of taking Chlorprothixene Zentiva or after the patient's transfer from another neuroleptic, during combined use with other psychoactive drugs or after increasing the dose.

From ethanol intake, as well as exposure to sun exposure and extreme high temperatures abstaining is recommended.

Cancellation of therapy should be gradual, this will reduce the likelihood of developing withdrawal syndrome.

Influence on the ability to drive vehicles and complex mechanisms

Patients should be careful while driving with Chlorprothixene Zentiva.

Application during pregnancy and lactation

According to the instructions, Chlorprothixene Zentiva should not be used during pregnancy / lactation, if possible.

Childhood use

Chlorprothixene Zentiva therapy is contraindicated in patients under 6 years of age.

With impaired renal function

Chlorprothixene Zentiva according to indications with concomitant renal failure must be used under medical supervision.

For violations of liver function

Chlorprothixene Zentiva at liver failure must be used under medical supervision.

Drug interactions

• ethanol and ethanol-containing drugs, anesthetics, opioid analgesics, sedatives, hypnotics, antipsychotics: the inhibitory effect of chlorprothixene on the central nervous system increases;
• antiepileptic drugs (in patients with epilepsy): the seizure threshold decreases (additional dose adjustment is required);
• m-anticholinergics, antihistamines and antiparkinsonian drugs: the anticholinergic effect of chlorprothixene is enhanced;
• phenothiazines, metoclopramide, haloperidol, reserpine: the appearance of extrapyramidal disorders may occur;
• levodopa: its effectiveness decreases;
• phenylephrine: the vasoconstrictor effect may decrease;
• dopamine (in high doses), epinephrine and ephedrine: peripheral vasoconstrictor action may be perverted;
• epinephrine: arterial hypotension and tachycardia may develop;
• antihypertensive drugs: their effect is enhanced;
• quinidine: the risk of developing adverse reactions from the heart increases;
• guanethidine: the hypotensive effect is reduced;
• bromocriptine: hyperprolactinemia may develop, which requires correction of the dosage regimen;
• ototoxic drugs (especially antibiotics): chlorprothixene can mask the symptoms of ototoxicity (such as tinnitus, dizziness).

Analogs

The analogue of Chlorprothixene Zentiva is Truxal.

Terms and conditions of storage

Store at temperatures up to 25 ° C. Keep out of the reach of children.

Shelf life is 3 years.

Trade name of the drug: Vitamin E Zentiva

Dosage form:

capsules

Composition:

1 capsule contains vitamin E (tocopherol acetate) 100 mg, 200 mg or 400 mg
Excipients: sunflower oil, gelatin, glycerol 75%, methylparaben, crimson dye Rubor ponceau 4R (E 124), purified water.

Description:
Red, oval capsules filled with clear light yellow oil.

Pharmacotherapeutic group:

vitamin

ATX code: A11NA03

Pharmacological properties
Has an antioxidant effect, participates in the biosynthesis of heme and proteins, cell proliferation, tissue respiration, and others critical processes tissue metabolism, prevents hemolysis of erythrocytes, reduces increased permeability and capillary fragility. Essential for the development and functioning of connective tissue, smooth and skeletal muscles, and for strengthening the walls blood vessels... Takes part in the metabolism of nucleic acids and prostaglandins, cellular respiratory cycle, in the synthesis of arachidonic acid. It is a natural antioxidant, inhibits lipid peroxidation by free radicals. Activates phagocytosis and is used to maintain normal erythrocyte resistance. In large doses, it prevents platelet aggregation. It has a pronounced positive effect on the human reproductive system, slows down the development of atherosclerotic vascular changes.

Pharmacokinetics:
When taken orally, 20% -40% is absorbed (the presence of bile and the normal functioning of the pancreas are necessary). When the dose is increased, the degree of absorption decreases. The optimal concentration in the blood is 10-15 mg / l. Excretion is mainly in the feces.
Less than 1% is excreted in the urine as glucuronides and other metabolites.

Indications for use

prevention and treatment of vitamin E hypovitaminosis;

in complex therapy with hormonal treatment violations menstrual cycle, degenerative and proliferative changes in the joints and ligamentous apparatus of the spine, with muscular dystrophy, with amyotrophic lateral sclerosis;

the state of convalescence after illnesses;

inadequate and unbalanced nutrition

elevated physical exercise.

Contraindications
Hypersensitivity to the components of the drug, acute heart attack myocardium, childhood.

Carefully - in patients with severe cardiosclerosis, myocardial infarction, with an increased risk of thromboembolism; hypoprothrombinemia caused by vitamin K deficiency may worsen when vitamin E is used at a dose of more than 400 IU.

Application during pregnancy and breastfeeding.
During pregnancy and breastfeeding, taking the drug only on the recommendation of a doctor.

Method of administration and dosage
Capsules 100 mg: adults, 2-4 capsules per day.
Capsules 200 mg: adults 1-2 capsules per day.
Capsules 400 mg: adults 1 capsule per day.
For menstrual irregularities (as an adjunct to hormone therapy) 300-400 mg every other day sequentially, starting from the 17th day of the cycle.

Side effect
Allergic reactions; from the gastrointestinal tract: diarrhea, nausea, gastralgia. Rarely, patients with a predisposition develop creatinuria, increased creatine kinase activity, increased serum cholesterol levels, thrombophlebitis, pulmonary thromboembolism, and thrombosis.

Overdose
High doses of vitamin E (400-800 mg per day for a long time) can cause visual impairment, diarrhea, dizziness, headache, nausea, severe fatigue, fainting, white hair growth in areas of alopecia with epidermolysis blister.
Very high doses (exceeding 800 mg for a long time) can cause bleeding in patients with vitamin K deficiency; they can disrupt hormone metabolism thyroid gland and to increase the risk of thrombophlebitis and thromboembolism in sensitive patients.
Treatment: symptomatic, drug withdrawal.

Interaction with other medicinal products
Strengthens the effect of glucocorticosteroids, non-steroidal anti-inflammatory drugs, cardiac glycosides. Increases the effectiveness of antiepileptic drugs in patients with epilepsy (in whom the content of lipid peroxidation products in the blood is increased).
Iron increases the daily requirement for vitamin E. Vitamin E enhances the effect of anticoagulants if doses exceed 400 IU per day.
The simultaneous intake of other vitamin complexes containing vitamin E is not recommended in order to avoid pre-dosage.
High-dose vitamin E supplementation can cause vitamin A deficiency in the body.
The simultaneous use of vitamin E at a dose of more than 400 IU per day with anticoagulants (coumarin and indandione derivatives) increases the risk of developing hypothrombinemia and bleeding.
Cholestyramine, colestipol, mineral oils reduce absorption.

special instructions
With congenital epidermolysis bullosa, white hair may begin to grow in areas affected by alopecia.

Release form
Capsules 100 mg, 200 mg: 30 capsules in dark glass bottles.
Capsules 400 mg: 20 or 30 capsules in dark glass vials.
Each bottle along with instructions for medical use placed in a cardboard box.

Storage conditions
At a temperature of 15 to 25 ° C in a dry, dark place.
Keep out of the reach of children.

Shelf life
3 years.
Do not use after the expiration date printed on the package.

Dispensing from pharmacies
Without recipe.

Manufacturer:

"ZENTIVA as", Slovak Republic
Nitrianska 100, 920 27 Glohovec, Slovak Republic

Moscow office address:
119017, Moscow, st. Bolshaya Ordynka, 40, bldg. 4