Truxal® [Chlorprotixen]

Pharmacological properties

chlorprotixen is a neuroleptic of the thioxanthene group. the antipsychotic effect of antipsychotics is due to the blocking of dopamine receptors, as well as the likely involvement of 5-nt (5-hydroxytryptamine) receptors in the blockade process.

Chlorprotixen has a high affinity for 5-HT₂receptors and α₁-adrenoreceptors and in this respect is similar to high-dose phenothiazines (levomepromazine, chlorpromazine, thioridazine) and the atypical antipsychotic clozapine. It is characterized by high histamine (N₁) an affinity similar to that of diphenhydramine. Chlorprotixen has a high affinity for M-cholinergic receptors. The receptor binding profile is similar to that of clozapine, although chlorprotixen has an almost 10-fold greater affinity for dopamine receptors (unlike phenothiazine derivatives) and dopamine receptors (affinity is almost 10 times higher than for clozapine).

Truxal is a sedative antipsychotic with a wide range of indications.

Truxal attenuates or eliminates anxiety, obsessive states, psychomotor agitation, anxiety, nervousness and insomnia, as well as hallucinations, mania, and other psychotic symptoms. In low doses it has an antidepressant effect, and therefore is used to treat a number of mental disorders, including those accompanied by syndromes of anxiety, anxiety and depression; psychosomatic disorders.

Chlorprotixen is not addictive, addictive, and is not accompanied by the development of tolerance to the action of the drug. Thus, chlorprotixen is effective in the treatment of both psychotic conditions and a wide range of other mental disorders. In addition, Truxal enhances the action of analgesics, has its own analgesic, anticonvulsant and antiemetic effect.

Pharmacokinetics After oral administration C_max in blood plasma is reached after approximately 2 hours (range - 0.5-6 hours). Average oral bioavailability is 12% (range - 5–32%). Binding to plasma proteins - 99%. Chlorprothixene crosses the placental barrier.

The metabolism of chlorprotixen passes mainly through sulfoxidation and N-demethylation.

T_½ approximately 16 hours (4–33 hours). Systemic clearance - about 1.2 l / min. Excretion occurs with feces and urine.

Chlorprotixen is excreted in small amounts in breast milk. The ratio of the concentration of milk / blood plasma is 1.2 / 2.6.

Information on pharmacokinetic parameters for impaired liver, kidney and elderly patients is not available.

Differences between the concentration of chlorprotixen in blood plasma or the elimination rate in patients of the control group and patients with alcoholism have not been established, regardless of the presence or absence of alcohol intoxication in the latter group.

Indications

• Schizophrenia and other psychoses associated with psychomotor agitation, anxiety and anxiety; treatment of withdrawal from alcoholism and drug addiction; depressive syndromes, neuroses, psychosomatic disorders, accompanied by anxiety, tension, agitation, insomnia, sleep disturbance; epilepsy and oligophrenia, accompanied by mental disorders such as eretism, agitation, mood lability and behavior disorders; chronic pain syndrome (to potentiate the action of analgesics); in geriatrics - hyperactivity, agitation, increased irritability, confusion, anxiety, behavior and sleep disorders; in pediatrics, behavioral and sleep disorders.

Application

Adults. Tablets are taken orally with water.

The dose is set individually in accordance with the condition of the patient.At the beginning of treatment, the drug is usually prescribed in low doses, which should be increased to achieve the optimal clinical effect as quickly as possible, depending on the individual response to treatment.

Schizophrenia and other psychotic conditions, mania. The initial dose is 50-100 mg / day, with a gradual increase in dose until a clinical effect is achieved. Usually the optimal therapeutic dose is 300 mg / day, but can be increased to 1200 mg / day if necessary. The maintenance dose in most cases is 100-200 mg / day. Given the sedative effect of the drug, the daily dose is divided into 3 doses, with daily doses lower than the dose taken at bedtime.

Treatment of abstinence in patients with alcoholism and drug addiction. Assign 500 mg / day, divided into several doses for 7 days. After overcoming the period of withdrawal, the dose is gradually reduced. A maintenance dose of 25 + 25 + 50 mg (1 + 1 + 2 25 mg tablets) allows you to stabilize the condition and reduce the risk of relapse. After a while, the dose can be reduced.

Depressive syndromes, neurosis, psychosomatic disorders. The minimum dose is 25 mg / day, which is gradually increased to 75–100 mg / day, in severe cases - up to 150 mg / day. The daily dose is divided into 3 doses, while the morning dose should be ¹/₃ evening dose.

Sleep disturbances. Assign 25 mg 1 hour before bedtime.

Epilepsy and oligophrenia with mental disorders. Assign 100-125 mg / day. Patients with epilepsy must be prescribed anticonvulsants in an adequate maintenance dose.

Chronic pain Possible combination with analgesics. The dose is gradually increased from 75-100 mg to 200-300 mg / day.

In geriarthria, the dose of the drug is set individually, usually it is 25–75 mg / day.

In pediatrics - prescribed for children over the age of 3 years in a dose of 0.5–2 mg / kg of body weight per day.

Impaired renal or hepatic function. A careful selection of the dose and, if possible, determination of the level of the drug in the blood serum is necessary.

Contraindications

Hypersensitivity to any of the components of the drug, vascular insufficiency (circulatory collapse), inhibition of central nervous system of various origins (for example, as a result of intoxication caused by alcohol, barbiturates, opioid agents), coma.

Chlorprotixen may cause prolongation of the Q – T interval. Persistent prolongation of the Q – T interval may increase the risk of malignant arrhythmias. Therefore, Truxal is contraindicated in patients with a history of clinically significant changes in the cardiovascular system (for example, bradycardia of 50 beats / min, recent myocardial infarction, decompensated heart failure, cardiac hypertrophy, arrhythmias if the patient is treated with class IIA antiarrhythmic drugs and ІІІ) and patients with a history of ventricular arrhythmias or Torsade de Pointes arrhythmias.

Truxal is contraindicated in patients with uncorrected hypokalemia and hypomagnesemia.

Truxal is contraindicated in patients with hereditary syndrome of an extended Q – T interval or established acquired extended Q – T interval (Q – TC 450 ms in men and 470 ms in women). Combined use with drugs that significantly extend the Q – T interval is also contraindicated.

Children under the age of 3 years.

Side effects

Side effects in most cases are dose-dependent. their frequency and severity are more pronounced at the beginning of therapy and decrease with further treatment.

Extrapyramidal symptoms may develop, especially in the initial phase of therapy. In most cases, they are corrected by a decrease in dosage and / or prescription of antiparkinsonian drugs. Regular prophylactic use of the latter is not recommended. If side effects occur, a dose reduction is recommended, and if possible, temporarily interrupt the course of chlorprotixen therapy.In the case of persistent akathisia, benzodiazepine or propranolol is recommended.

The frequency of adverse reactions shown in the table below is defined as: very often (≥1 / 10); often (≥1 / 100, but 1/10); infrequently (≥1 / 1000, but 1/100); rarely (≥1 / 10,000, but 1/1000) or very rarely (1/10 000).

There are reports of rare cases of prolongation of the Q – T interval, ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, Torsade de Pointes arrhythmias, and sudden death with the use of drugs belonging to the therapeutic class of antipsychotics, including chlorprotixen.

Sudden discontinuation of chlorprotixen can cause withdrawal symptoms, the most common of which are nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, myalgia, paresthesia, insomnia, anxiety, anxiety and agitation. Patients may also experience dizziness, alternating sensations of warmth or cold, and tremors. Symptoms usually begin within 1–4 days after discontinuation of the drug and decrease over 7–14 days.

special instructions

The likelihood of developing a malignant antipsychotic syndrome (hyperthermia, rigidity of the skeletal muscles, confusion, instability of the cardiovascular system) exists with the appointment of any antipsychotic. the risk is potentially higher when using several drugs. among fatal cases, patients with existing organic syndrome, mental retardation, abuse of opiates and alcohol predominate.

Treatment: discontinuation of antipsychotics, symptomatic and general supportive measures. Directly acting muscle relaxants (dantrolene), dopamine receptor agonists (bromocriptine) can be used.

In patients with a decrease in the depth of the anterior chamber of the eye and a narrowing of its angle, attacks of acute glaucoma may occur due to the expansion of the pupil.

When using some atypical antipsychotics in a randomized, placebo-controlled study, a 3-fold increase in the risk of cerebrovascular adverse events was observed among a population of patients with dementia. The mechanism of this increased risk is unknown. An increased risk cannot be excluded for other antipsychotics and other patient populations. Chlorprotixen should be used with caution in patients with risk factors for stroke.

Chlorprotixen should be used with caution in patients with a history of cardiovascular disease or a hereditary Q – T prolongation syndrome due to the high risk of malignancy.