Pharmacological properties of the drug Chlorprothixene
Chlorprothixene is an antipsychotic, a thioxanthene derivative. It also has sedative, antiemetic, antidepressant and antihistamine effects. The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical systems. It has antiserotonin, cholinergic and adrenergic blocking activity. The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect - blockade of dopamine receptors of the hypothalamus; antihistamine - blockade of H1 receptors. Quickly absorbed from the digestive tract; After oral administration, the effect occurs within 20 minutes. It undergoes first-pass metabolism in the intestinal walls and liver. Has a first pass effect through the liver. Penetrates through the placental barrier and into breast milk. Metabolized in the body. It is excreted in urine and feces, primarily in the form of metabolites (at a daily dose of 300 mg - about 29% as chlorprothixene, 41% as chlorprothixene sulfoxide). The half-life is 8–12 hours.
Indications for use of the drug Chlorprothixene
In psychiatry and neurology - depression, including reactive and neurotic with anxiety symptoms, states of excitation associated with a feeling of fear and tension, dyscirculatory encephalopathy, traumatic brain injury, delirium tremens, sleep disorders accompanying an anxious state, the need for long-term therapy for states of excitement and anxiety, psychosomatic, neurotic and behavioral disorders in children; in surgery - premedication, postoperative period, anxiety in patients with burns; in dermatology - dermatoses accompanied by persistent skin itching (neurodermatitis, lichen planus, seborrheic dermatitis, etc.); in gynecology - depression during menopause; in therapy and pediatrics - sleep disturbances in somatic diseases, convulsive cough, spastic state of the digestive tract, vomiting, allergic reactions.
Chlorprothixen
When using any antipsychotic, there is a risk of developing neuroleptic malignant syndrome (hyperthermia, muscle rigidity, fluctuations in consciousness, instability of the autonomic nervous system).
Patients with pre-existing psychoorganic syndrome, mental retardation, as well as those who abuse opiates and alcohol make up a significant proportion of deaths.
Treatment
: withdrawal of antipsychotic. Symptomatic therapy and general supportive treatment measures. Dantrolene and bromocriptine may be effective. After taking antipsychotics by mouth, symptoms may persist for more than one week.
Acute attacks of glaucoma due to pupil dilation can occur in patients with the rare shallow anterior chamber syndrome and in patients with a narrow anterior chamber angle.
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 long QT interval (see section "Caution").
Before starting treatment, an ECG examination should be performed.
The use of the drug Chlorprothixene is contraindicated if the QTc interval at the initial measurement exceeds 450 ms in men and 470 ms in women (see section "Contraindications"). During treatment, the need for ECG monitoring should be assessed on an individual basis. During the treatment period, the dose should be reduced if the QT interval increases, and therapy should be discontinued if the QTc interval is >500 ms.
It is recommended to periodically monitor water and electrolyte balance indicators.
The simultaneous use of other antipsychotic drugs should be avoided (see section "Interaction with other drugs").
Like other antipsychotics, Chlorprothixene should be used with caution in patients with psychoorganic syndrome, seizures, liver, kidney and cardiovascular diseases in the later stages, as well as patients with myasthenia gravis and benign prostatic hyperplasia.
Caution must be exercised
when using the drug in patients with:
- pheochromocytoma,
- prolactin-dependent tumors,
- severe arterial hypotension or orthostatic dysregulation,
- Parkinson's disease,
- diseases of the hematopoietic system,
- hyperthyroidism,
- urinary disorders, urinary retention,
- pyloric stenosis (pyloric stenosis), intestinal obstruction (see section “With caution”).
Like other psychotropic drugs, Chlorprothixene may affect blood glucose levels in patients with diabetes mellitus, which may require dose adjustment of antidiabetic drugs (insulin or oral hypoglycemic drugs).
Patients undergoing long-term treatment, especially with high doses, are subject to careful monitoring over time with periodic assessment of the need to reduce the maintenance dose.
Cases of venous thromboembolism (VTE) have been reported while taking antipsychotic drugs. Due to the fact that patients treated with antipsychotic drugs are often at risk for developing VTE, risk factors for VTE should be identified before and during treatment with chlorprothixene and precautions taken.
It has been reported that antipsychotics with α-adrenergic blocking effects may cause priapism; it is possible that chlorprothixene also has this property. If severe priapism occurs, medical intervention may be required. Patients should be warned about the need to urgently seek medical help if objective and subjective signs of priapism appear.
Use of the drug in children and adolescents under 18 years of age
Chlorprothixene is not recommended for use in children and adolescents. A sufficient number of clinical studies aimed at studying the effectiveness and safety of the use of chlorprothixene for the treatment of children and adolescents have not been conducted.
Elderly patients
Cerebrovascular adverse reactions
According to randomized placebo-controlled trials in populations of patients with dementia, the use of some atypical antipsychotics was associated with an approximately 3-fold increase in the risk of cerebrovascular adverse reactions. The mechanism by which this risk increases is unknown. A similar increase in risk cannot be excluded for other antipsychotics and other patient groups. In patients with risk factors for stroke, Chlorprothixene should be used with caution (see section "With caution").
Elderly patients are especially at risk of developing orthostatic hypotension.
Increased mortality in older patients with dementia
Data from two large observational studies showed that older patients with dementia taking antipsychotic drugs had a nonsignificant increased risk of death compared with patients not taking antipsychotic drugs. There is no sufficient data to accurately assess the magnitude of the risk and the reasons for its increase.
Chlorprothixene is not registered for the treatment of behavioral disorders in elderly patients with dementia.
To avoid the development of withdrawal syndrome, it is necessary to stop treatment with Chlorprothixene gradually.
Excipients
Chlorprothixene tablets contain lactose monohydrate. Patients with rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.
Use of the drug Chlorprothixene
Adults with neuroses are prescribed 10-15 mg at night, in more severe cases - 30 mg at night, in exceptional cases an additional 15 mg is prescribed in the morning. For psychosis, 100–600 mg/day is prescribed in 1 dose at night; if it is necessary to use the daily dose during the day, it is distributed so that the highest dose is taken in the evening. For skin itching, 15–100 mg/day is prescribed in 4 divided doses. Children with neuroses are prescribed 5–30 mg/day, with psychoses – 10–200 mg/day. For elderly patients, dose adjustment is recommended.
Chlorprothixene
When using any antipsychotic, there is a risk of developing neuroleptic malignant syndrome (hyperthermia, muscle rigidity, fluctuation of consciousness, instability of the autonomic nervous system). Patients with pre-existing psychoorganic syndrome, mental retardation, as well as those who abuse opiates and alcohol make up a significant proportion of deaths.
Treatment
: withdrawal of antipsychotic. Symptomatic therapy and general supportive treatment measures. Dantrolene and bromocriptine may be effective. After taking antipsychotics by mouth, symptoms may persist for more than one week.
Patients with rare conditions such as a small anterior chamber and a narrow angle may experience acute attacks of glaucoma due to pupil dilation.
Due to the risk of developing malignant arrhythmias, chlorprothixene should be used with caution in patients with a history of cardiovascular disease and in patients with a family history of long QT interval.
ECG monitoring is necessary before starting treatment. Chlorprothixene is contraindicated if the QTc interval at baseline is more than 450 ms in men and 470 ms in women (see section "Contraindications").
During therapy, the need for ECG monitoring should be assessed by the physician, taking into account the individual characteristics of the patient. During treatment, reduce the dosage if the QT interval is prolonged or discontinue therapy if the QTc is > 500 ms.
During treatment, periodic assessment of electrolyte balance is recommended.
The simultaneous use of other antipsychotic drugs should be avoided (see section "Interaction with other drugs").
Like other antipsychotics, chlorprothixene should be used with caution in patients with psychoorganic syndrome, seizures, liver, kidney and cardiovascular diseases in the later stages, as well as patients with myasthenia gravis and benign prostatic hyperplasia.
Caution must be exercised when using the drug in patients with
- pheochromocytoma,
- prolactin-dependent tumors,
- severe arterial hypotension or orthostatic dysregulation,
- Parkinson's disease,
- diseases of the hematopoietic system,
- hyperthyroidism,
- urinary problems, urinary retention,
- pyloric stenosis (pyloric stenosis), intestinal obstruction.
Like other psychotropic drugs, chlorprothixene may change the concentration of insulin and glucose in the blood, so patients with diabetes may require dosage adjustments of antidiabetic drugs.
Patients undergoing long-term treatment, especially with high doses, are subject to careful monitoring over time with periodic assessment of the need to reduce the maintenance dose.
Cases of venous thromboembolism (VTE) have been reported while taking antipsychotic drugs. Due to the fact that patients treated with antipsychotic drugs are often at risk for developing VTE, risk factors for VTE should be identified before and during treatment with chlorprothixene and precautions taken.
It has been reported that antipsychotics with α-adrenergic blocking effects may cause priapism; it is possible that chlorprothixene also has this property. If severe priapism occurs, medical intervention may be required.
Patients should be warned about the need to urgently seek medical help if objective and subjective signs of priapism appear.
Use of the drug in children and adolescents under 18 years of age
Chlorprothixene is not recommended for use in adolescent children. A sufficient number of studies have not been conducted to study the effectiveness and safety of the use of chlorprothixene for the treatment of children and adolescents.
Elderly patients
Cerebrovascular adverse reactions
In randomized placebo-controlled clinical trials of certain atypical antipsychotics in patients with dementia, a 3-fold increase in the risk of cerebrovascular adverse reactions was observed. The mechanism for this increased risk is unknown.
An increased risk cannot be ruled out when using other antipsychotics in other groups of patients.
Chlorprothixene should be used with caution in patients at risk of stroke. Elderly individuals are particularly at risk of developing orthostatic hypotension.
Increased mortality in older patients with dementia
Data from two large observational studies showed that older patients with dementia taking antipsychotic drugs had a nonsignificant increased risk of death compared with patients not taking antipsychotic drugs. There is no sufficient data to accurately assess the magnitude of the risk and the reasons for its increase. Chlorprothixene is not registered for the treatment of behavioral disorders in elderly patients with dementia.
Excipients
The tablets contain lactose monohydrate and sucrose. This drug should not be used in patients with rare hereditary problems such as lactose or fructose intolerance, lactase deficiency or glucose-galactose malabsorption, sucrase/isomaltase deficiency.
Side effects of the drug Chlorprothixene
Possible psychomotor retardation, mild extrapyramidal syndrome, orthostatic hypotension, increased fatigue, dizziness, opacification of the cornea and lens with possible visual impairment, jaundice, agranulocytosis, leukocytosis, leukopenia, hemolytic anemia, amenorrhea, galactorrhea, gynecomastia, impaired carbohydrate metabolism, decreased potency and libido , increased appetite leading to weight gain, photosensitivity, photodermatitis. Side effects caused by anticholinergic effects: a feeling of dry mouth, tachycardia, increased sweating, frequent hot flashes, impaired accommodation, constipation, urinary disorders.
Chlorprothixene sanofi 50 mg 50 pcs. film-coated tablets
pharmachologic effect
Antipsychotic drug (neuroleptic), thioxanthene derivative.
It has antipsychotic, antidepressant, sedative, antiemetic effects, and has alpha-adrenergic blocking activity. It is believed that the antipsychotic effect is associated with blockade of postsynaptic dopamine receptors in the brain. The antiemetic effect is associated with blockade of the chemoreceptor trigger zone of the medulla oblongata. The sedative effect is due to an indirect weakening of the activity of the reticular system of the brain stem. Suppresses the release of most hormones of the hypothalamus and pituitary gland. However, as a result of blockade of the prolactin inhibitory factor, which inhibits the release of prolactin from the pituitary gland, the concentration of prolactin increases.
The chemical structure and pharmacological properties of thioxanthenes are similar to piperazine derivatives of phenothiazine.
Composition and release form Sanofi chlorprothixene 50 mg 50 pcs. film-coated tablets
Tablets - 1 tablet:
- Active substance: chlorprothixene hydrochloride 50 mg.
- Excipients: corn starch, lactose monohydrate, sucrose, calcium stearate, talc.
- Film shell composition: hypromellose 2910/5, macrogol 6000, macrogol 300, talc, aluminum varnish based on sunset yellow dye (E110).
10 pieces. - blisters (5) - cardboard packs.
Description of the dosage form
Orange film-coated tablets, round, biconvex; fracture appearance - the core is white to almost white.
Directions for use and doses
Individual. For oral administration for adults, the daily dose varies from 10 mg to 600 mg, for children - from 5 mg to 200 mg. The frequency of administration and duration of treatment are determined by the indications.
Pharmacokinetics
Metabolized in the liver. It is excreted primarily by the kidneys.
Indications for use Chlorprothixene sanofi 50 mg 50 pcs. film-coated tablets
Psychoses and psychotic states, accompanied by anxiety, fear, psychomotor agitation, aggressiveness, incl. for depressive-paranoid, circular schizophrenia, for simple sluggish schizophrenia with psychopath-like and neurosis-like symptoms and for other mental illnesses; discirculatory encephalopathy, traumatic brain injury (as part of combination therapy), alcoholic delirium; sleep disorders due to somatic diseases; the need for long-term therapy for states of excitation and anxiety, psychosomatic, neurotic and behavioral disorders in children; convulsive cough, spastic conditions in the gastrointestinal tract; premedication; dermatoses accompanied by persistent itching; allergic reactions.
Contraindications
CNS depression, incl. in case of intoxication with alcohol, barbiturates and other drugs that have a depressing effect on the central nervous system, pathological changes in the blood picture, myelodepression, pregnancy, lactation, hypersensitivity to chlorprothixene.
Application of Chlorprothixene sanofi 50 mg 50 pcs. film-coated tablets during pregnancy and breastfeeding
Contraindicated for use during pregnancy and lactation.
special instructions
It should not be used for epilepsy, a tendency to collapse, parkinsonism, heart defects in the stage of decompensation, tachycardia, cerebral atherosclerosis, severe liver and kidney dysfunction, hematopoietic disorders, cachexia, and in old age.
If it is necessary to use chlorprothixene, the risks and benefits of treatment should be compared in patients with chronic alcoholism, diseases of the cardiovascular system (increased risk of developing transient arterial hypotension), Reye's syndrome, as well as glaucoma or a predisposition to it, peptic ulcer of the stomach and duodenum, delayed urine, Parkinson's disease, epileptic seizures, hypersensitivity to other thioxanthenes or phenothiazines.
When using chlorprothixene, false-positive results of an immunological pregnancy test using urine, as well as false-positive results of a urine test for bilirubin, are possible.
During the treatment period, avoid drinking alcohol.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, you should refrain from engaging in potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Side effects Chlorprothixene sanofi 50 mg 50 pcs. film-coated tablets
From the side of the central nervous system: possible psychomotor inhibition, mild extrapyramidal syndrome, increased fatigue, dizziness; in isolated cases, a paradoxical increase in anxiety is possible, especially in patients with mania or schizophrenia.
From the digestive system: cholestatic jaundice is possible.
From the cardiovascular system: possible tachycardia, ECG changes, orthostatic hypotension.
From the organ of vision: possible clouding of the cornea and lens with visual impairment.
From the hematopoietic system: possible agranulocytosis, leukocytosis, leukopenia, hemolytic anemia.
From the endocrine system: frequent hot flashes, amenorrhea, galactorrhea, gynecomastia, weakened potency and libido are possible.
On the metabolic side: increased sweating, impaired carbohydrate metabolism, increased appetite with increased body weight are possible.
Dermatological reactions: photosensitivity, photodermatitis are possible.
Effects due to anticholinergic action: dry mouth, constipation, accommodation disturbances, dysuria.
Drug interactions
When used simultaneously with anesthetics, opioid analgesics, sedatives, hypnotics, antipsychotics, ethanol, ethanol-containing drugs, the inhibitory effect on the central nervous system is enhanced.
When used simultaneously with antihypertensive drugs, the hypotensive effect is enhanced.
When used simultaneously with anticholinergic, antihistamine, antiparkinsonian drugs, the anticholinergic effect is enhanced.
When used simultaneously with drugs that cause extrapyramidal reactions, an increase in the frequency and severity of extrapyramidal reactions is possible; with levodopa - the antiparkinsonian effect of levodopa may be inhibited; with lithium carbonate - severe extrapyramidal symptoms and neurotoxic effects are possible.
When used concomitantly with epinephrine, it is possible to block the alpha-adrenergic effects of epinephrine and, as a result, develop severe arterial hypotension and tachycardia.
When used simultaneously with phenothiazines, metoclopramide, haloperidol, reserpine, the development of extrapyramidal disorders is possible; with quinidine - an increased inhibitory effect on the heart is possible.
Drug interactions Chlorprothixene
Combination with antidepressants (amitriptyline, nortriptyline, imipramine, dosulenin) is acceptable. The depressant effect of chlorprothixene is enhanced when taken simultaneously with ethanol, anesthetics, opioid analgesics, sedatives, hypnotics and antipsychotics. Atropine enhances the anticholinergic effect of chlorprothixene. Chlorprothixene potentiates the effect of antihypertensive drugs.
List of pharmacies where you can buy Chlorprothixene:
- Moscow
- Saint Petersburg
Chlorprothixene (Truxal)
Contraindications
CNS depression, incl. in case of intoxication with alcohol, barbiturates and other drugs that have a depressing effect on the central nervous system, pathological changes in the blood picture, myelodepression, pregnancy, lactation, hypersensitivity to chlorprothixene.
Dosage
Individual. For oral administration for adults, the daily dose varies from 10 mg to 600 mg, for children - from 5 mg to 200 mg. The frequency of administration and duration of treatment are determined by the indications.
Side effects
- From the side of the central nervous system: possible psychomotor inhibition, mild extrapyramidal syndrome, increased fatigue, dizziness; in isolated cases, a paradoxical increase in anxiety is possible, especially in patients with mania or schizophrenia.
- From the digestive system: cholestatic jaundice is possible.
- From the cardiovascular system: possible tachycardia, ECG changes, orthostatic hypotension.
- From the organ of vision: possible clouding of the cornea and lens with visual impairment.
- From the hematopoietic system: possible agranulocytosis, leukocytosis, leukopenia, hemolytic anemia.
- From the endocrine system: frequent hot flashes, amenorrhea, galactorrhea, gynecomastia, weakened potency and libido are possible.
- On the metabolic side: increased sweating, impaired carbohydrate metabolism, increased appetite with increased body weight are possible.
Dermatological reactions: photosensitivity, photodermatitis are possible.
Effects due to anticholinergic action: dry mouth, constipation, accommodation disturbances, dysuria.
Drug interactions
When used simultaneously with anesthetics, opioid analgesics, sedatives, hypnotics, antipsychotics, ethanol, ethanol-containing drugs, the inhibitory effect on the central nervous system is enhanced.
When used simultaneously with antihypertensive drugs, the hypotensive effect is enhanced.
When used simultaneously with anticholinergic, antihistamine, antiparkinsonian drugs, the anticholinergic effect is enhanced.
When used simultaneously with drugs that cause extrapyramidal reactions, an increase in the frequency and severity of extrapyramidal reactions is possible; with levodopa - the antiparkinsonian effect of levodopa may be inhibited; with lithium carbonate - severe extrapyramidal symptoms and neurotoxic effects are possible.
When used concomitantly with epinephrine, it is possible to block the alpha-adrenergic effects of epinephrine and, as a result, develop severe arterial hypotension and tachycardia.
When used simultaneously with phenothiazines, metoclopramide, haloperidol, reserpine, the development of extrapyramidal disorders is possible; with quinidine - an increased inhibitory effect on the heart is possible.
special instructions
It should not be used for epilepsy, a tendency to collapse, parkinsonism, heart defects in the stage of decompensation, tachycardia, cerebral atherosclerosis, severe liver and kidney dysfunction, hematopoietic disorders, cachexia, and in old age.
If it is necessary to use chlorprothixene, the risks and benefits of treatment should be compared in patients with chronic alcoholism, diseases of the cardiovascular system (increased risk of developing transient arterial hypotension), Reye's syndrome, as well as glaucoma or a predisposition to it, peptic ulcer of the stomach and duodenum, delayed urine, Parkinson's disease, epileptic seizures, hypersensitivity to other thioxanthenes or phenothiazines.
When using chlorprothixene, false-positive results of an immunological pregnancy test using urine, as well as false-positive results of a urine test for bilirubin, are possible.
During the treatment period, avoid drinking alcohol.
Impact on the ability to drive vehicles and operate machinery
During the treatment period, you should refrain from engaging in potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Pregnancy and lactation
Contraindicated for use during pregnancy and lactation.
For impaired renal function
Should not be used in cases of severe renal impairment.
For liver dysfunction
Should not be used in cases of severe liver dysfunction.
Use in old age
Should not be used in old age.
