Instructions Truxal film-coated tablets 25 mg container No. 100
Composition
active ingredient: chlorprothixene;
1 tablet contains 25 mg or 50 mg of chlorprothixene hydrochloride;
excipients: corn starch; lactose, monohydrate; copovidone; glycerol (85%); microcrystalline cellulose; croscarmellose sodium; talc; magnesium stearate; coating OPADRY OY-S-9478 brown.
Dosage form
Film-coated tablets.
Main physicochemical properties: 25 mg tablets are round, biconvex, film-coated tablets of dark brown color; 50 mg tablets are oval, biconvex, film-coated tablets of dark brown color.
Pharmacotherapeutic group
Psycholeptics. Antipsychotics. Thioxanthene derivatives. Chlorprothixene.
ATX code N05A F03.
Pharmacological properties
Pharmacodynamics
Chlorprothixene is a neuroleptic from the thioxanthene group.
The antipsychotic effect of neuroleptics is associated with the blockade of dopamine receptors, but also with the possible involvement of the blockade of 5-HT (5-hydroxytryptamine) receptors in this process.
Chlorprothixene has high affinity for 5-HT2 receptors and α1-adrenoceptors and is similar in this respect to the high-dose phenothiazines, levomepromazine, chlorpromazine, thioridazine and the atypical antipsychotic clozapine. It has a high histamine (H1) affinity, which is equal to that of diphenhydramine. Chlorprothixene exhibits high affinity for cholinergic muscarinic receptors. The receptor binding profile is quite similar to that of clozapine, although chlorprothixene has almost 10 times greater affinity for dopamine receptors.
Chlorprothixene is a sedative neuroleptic with a wide range of indications.
Chlorprothixene reduces or eliminates anxiety, obsessive states, psychomotor agitation, restlessness, nervousness and insomnia, as well as hallucinations, mania and other psychotic symptoms. In low doses, it has an antidepressant effect, which makes it acceptable for the treatment of mental disorders accompanied by anxiety-depression syndrome; psychosomatic disorders.
Chlorprothixene does not cause addiction, dependence or tolerance. Thus, chlorprothixene is effective in the treatment of both psychotic states and a wide range of other mental disorders. In addition, chlorprothixene enhances the effect of analgesics, has its own analgesic effect, antipruritic and antiemetic properties.
Pharmacokinetics
When chlorprothixene is administered orally, peak plasma levels are observed after approximately 2 hours (range 0.5–6 hours). The mean oral bioavailability is 12% (range 5–32%).
Plasma protein binding > 99%. Chlorprothixene crosses the placental barrier.
The metabolism of chlorprothixene occurs mainly through sulfonic acidification and N-demethylation.
The elimination half-life (T1/2β) is approximately 15 hours (range 3 to 29 hours). Systemic clearance (Cls) is approximately 1.2 l/min. Excretion occurs in the feces and urine.
Chlorprothixene passes into the milk of lactating women in small amounts. The milk/serum concentration ratio is 1.2-2.6.
There is no information on pharmacokinetic parameters in patients with reduced liver or kidney function or in elderly patients.
No difference in plasma concentration or elimination rate was found between the control group and alcoholics, regardless of whether they were sober or intoxicated at the time.
Indication
Schizophrenia and other psychoses with psychomotor restlessness, agitation and anxiety disorder.
Contraindication
Hypersensitivity to any component of the drug or to thioxanthene group agents.
Circulatory collapse, central nervous system depression of any origin (e.g., due to alcohol, barbiturate, or opioid intoxication), coma.
Chlorprothixene may cause QT prolongation. Persistent QT prolongation may increase the risk of malignant arrhythmias. Therefore, chlorprothixene is contraindicated in patients with a history of clinically significant cardiovascular disorders (e.g., bradycardia <50 bpm, recent acute myocardial infarction, uncompensated heart failure, cardiac hypertrophy, arrhythmias if class IA and III antiarrhythmics are prescribed) and in patients with a history of ventricular arrhythmias or torsades de pointes.
Chlorprothixene is contraindicated in patients with uncorrected hypokalemia and hypomagnesemia.
Chlorprothixene is contraindicated in patients with hereditary long QT syndrome or established acquired long QT (QTc greater than 450 msec in men and 470 msec in women).
Concomitant use with drugs that significantly prolong the QT interval.
Interaction with other medicinal products and other types of interactions
Combinations that require precautions when used.
Chlorprothixene may enhance the sedative effects of alcohol, barbiturates, and central nervous system inhibitors.
Neuroleptics may enhance or reduce the effect of antihypertensive agents; the hypotensive effect of guanethidine and similarly acting agents is weakened.
Tricyclic antidepressants and neuroleptics mutually inhibit each other's metabolism.
Chlorprothixene may reduce the effectiveness of levodopa and adrenergic agents, and the combination with metoclopramide and piperazine increases the risk of developing extrapyramidal disorders.
Neuroleptics are metabolized by the hepatic cytochrome P450 system. Drugs that are inhibitors of the CYP 2D6 system (e.g. paroxetine, fluoxetine, chloramphenicol, disulfiram, isoniazid, MAO inhibitors, oral contraceptives, and to a lesser extent buspirone, sertraline, or citalopram) may increase plasma levels of chlorprothixene.
Concomitant use of chlorprothixene and agents with anticholinergic activity enhances anticholinergic effects.
The antihistamine effect of chlorprothixene may attenuate or eliminate the alcohol/disulfiram reaction.
The QT prolongation associated with antipsychotic drugs may be exacerbated by concomitant use with other drugs that can significantly prolong the QT interval. The combination of such drugs is contraindicated. Relevant classes include:
class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide);
some antipsychotics (e.g. thioridazine);
some macrolides (e.g. erythromycin);
some antihistamines (e.g. terfenadine, astemizole);
some quinolones (e.g. gatifloxacin, moxifloxacin).
The list above is not exhaustive, and combination with other individual drugs that can significantly prolong the QT interval (e.g., cisapride, lithium) should be avoided.
Agents that alter electrolyte balance, such as thiazide diuretics (hypokalemia), and agents that increase chlorprothixene concentrations should also be used with caution as they may increase the risk of QT prolongation and malignant arrhythmias.
Application features
Truxal should be used with caution in patients with Parkinson's disease or organic brain syndrome, epileptic disorders, progressive liver, kidney or cardiovascular diseases, myasthenia gravis, prostatic hypertrophy or narrow-angle glaucoma. Truxal should be used with caution in elderly patients who are susceptible to orthostatic disorders.
Caution is required when used in patients with the following pathologies:
pheochromocytoma;
prolactin-dependent neoplasia;
severe hypotension;
diseases of the hematopoietic system;
hyperthyroidism;
Urination disorders, urinary retention, pyloric stenosis, intestinal obstruction.
The possibility of developing neuroleptic malignant syndrome (hyperthermia, muscle rigidity, impaired consciousness, autonomic dysfunction) exists with the use of any neuroleptic. Among patients in whom fatal outcomes have been observed, patients with existing organic syndrome, mental retardation, opiate and alcohol abuse predominate.
Treatment: Discontinue neuroleptics. Treat symptomatically and use general supportive measures. Dantrolene and bromocriptine may be used. Symptoms may persist for more than a week after oral neuroleptics are used.
Acute glaucoma attacks due to pupil dilation can occur in patients with the rare condition of shallow anterior chamber depth and narrow chamber angle.
Like other psychotropic drugs, chlorprothixene may alter the body's sensitivity to insulin and glucose, requiring correction of antidiabetic therapy in patients with diabetes.
Chlorprothixene should be used with caution in patients with a history of cardiovascular disease or hereditary QT prolongation syndrome due to the risk of malignant arrhythmias.
ECG monitoring is mandatory before starting treatment with chlorprothixene. Chlorprothixene is contraindicated if the QT interval during such examination is more than 450 msec in men or more than 470 msec in women.
During treatment, the need for ECG monitoring is determined individually for the patient. The dose is reduced if QT prolongs, and therapy is discontinued if QT is greater than 500 msec.
Periodic monitoring of electrolyte levels is recommended.
Concomitant use with other neuroleptics should be avoided.
Cases of venous thromboembolism (VTE) have been reported with the use of antipsychotics. Since patients treated with antipsychotics often have acquired risk factors for VTE, it is important to identify all possible risk factors for VTE before initiating and during treatment with chlorprothixene and take preventive measures.
Priapism has been reported with antipsychotics with α-adrenergic blocking effects, and chlorprothixene may share this potential. Severe priapism may require medical intervention. Patients should be advised to seek immediate medical attention if signs and symptoms of priapism develop.
Elderly patients
An approximately three-fold increased risk of cerebrovascular adverse events has been observed with some atypical antipsychotics in randomized, placebo-controlled clinical trials in the dementia population. The mechanism of this increased risk is unknown. An increased risk cannot be excluded for other antipsychotics and other patient populations. Chlorprothixene should be used with caution in patients with risk factors for stroke.
Increased risk of fatal outcomes in elderly patients with dementia:
Clinical trials have shown that elderly patients with dementia who are treated with antipsychotics have a slightly increased risk of death compared with those who are not treated with antipsychotics. There are insufficient data to estimate the magnitude of the risk, and the reason for the increased risk is unknown.
Chlorprothixene is not indicated for the treatment of behavioral disorders associated with dementia.
The drug should be prescribed with caution, given the risk of adverse effects, especially considering the rare (and potentially irreversible) tardive dyskinesia, and the dose and continuation of therapy should be regularly monitored.
Patients undergoing long-term treatment, especially at high doses, should be carefully monitored and periodically reassessed with the aim of reducing the dosage.
Truxal may lower the seizure threshold, therefore, in patients with epilepsy, antiepileptic treatment should be individually adapted.
Truxal may impair thermoregulation, so caution should be exercised when using the drug at extreme temperatures.
Truxal's effects on the CNS, as well as its antiemetic properties, may mask the symptoms of certain diseases.
Patients undergoing long-term treatment with Truxal should have their psychological and neurological status, blood tests, and liver function monitored regularly.
Excipients.
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Clinical experience in pregnant women is limited. Chlorprothixene should not be administered during pregnancy unless the expected benefit to the patient outweighs the potential risk to the fetus.
Neonates whose mothers have taken antipsychotics (including chlorprothixene) during the last trimester of pregnancy may be at risk of adverse reactions, including extrapyramidal symptoms or withdrawal symptoms, which may vary in severity and duration following delivery. Cases of agitation, hypertension, hypotension, tremor, somnolence, respiratory distress, or difficulty feeding have been reported. Therefore, neonates should be closely monitored.
Preclinical data are insufficient to assess reproductive toxicity.
Chlorprothixene is found in breast milk in low concentrations, and its effects on the infant are unlikely at therapeutic doses. The dose received by the infant in milk is approximately 2% of the maternal daily dose related to body weight. Breastfeeding may continue during treatment with chlorprothixene if clinically necessary, but it is recommended to monitor the infant, especially in the first four weeks after birth.
Fertility.
Hyperprolactinemia, galactorrhea, amenorrhea, ejaculation failure, and erectile dysfunction have been reported. These conditions may have a negative impact on female and/or male sexual function and fertility.
If clinically significant hyperprolactinemia, galactorrhea, amenorrhea, or sexual dysfunction occurs, dose reduction (if possible) or discontinuation should be considered. The effects are reversible upon discontinuation of the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
Truxal is a sedative. Truxal, like other major psychiatric disorders, can impair attention and reaction time, and can affect behavior and psychomotor function. Patients taking Truxal should not drive or operate dangerous machinery until they know how they react to the medication.
Method of administration and doses
Dosage should be selected individually. The initial dose should be low, then the dose should be increased relatively quickly until the optimal therapeutic effect is achieved.
Schizophrenia and other psychoses with psychomotor restlessness, agitation and anxiety disorder.
Initial dose 50–100 mg/day with gradual increase until optimal effect is achieved. The usual optimal dose is 300 mg/day, which in individual cases can be increased to 1200 mg/day, if necessary.
The maintenance dose is usually 100–200 mg/day.
Due to the strong sedative effect, lower doses should be taken during the day and higher doses in the evening.
Kidney and liver dysfunction
Careful dosing and, if possible, serum level determination are desirable.
Children
Chlorprothixene is not recommended for use in children under 18 years of age, as clinical studies of efficacy and safety in children and adolescents are insufficient.
Overdose
Symptoms: drowsiness, coma, shock, extrapyramidal disorders, hyper- or hypothermia.
In severe cases, kidney damage.
With simultaneous overdose with drugs that can affect cardiac activity, there have been cases of ECG changes, QT prolongation, torsades de pointes, cardiac arrest, and ventricular arrhythmias.
Treatment: symptomatic and supportive therapy. After ingestion, gastric lavage should be performed as soon as possible; activated charcoal may be administered. Measures should be taken to support the respiratory and cardiovascular systems. Adrenaline should not be used, as a further decrease in blood pressure may occur. Convulsions can be treated with diazepam, and extrapyramidal symptoms with biperiden.
For adults, doses of 2.5–4 g can be fatal, for children, approximately 4 mg/kg of body weight. Adults have survived after 10 g, and a three-year-old child after taking 1000 mg.
Side effects
Undesirable effects are in most cases dose-dependent. Their frequency and severity are more pronounced at the beginning of therapy and decrease with further treatment.
Extrapyramidal disorders may develop, especially in the initial phase of therapy. In most cases, they are corrected by reducing the dosage and/or antiparkinsonian drugs. Regular prophylactic use of the latter is not recommended. It is recommended to reduce the dose or, if possible, discontinue chlorprothixene therapy. In case of persistent akathisia, it is recommended to use a benzodiazepine or propranolol.
The frequency of adverse reactions listed in the table below is defined as:
very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000) or very rare (<1/10000).
| From the heart | Often | Tachycardia, rapid heartbeat. |
| Rare | QT prolongation on ECG. |
| Blood and lymphatic system disorders | Rare | Thrombocytopenia, neutropenia, leukopenia, agranulocytosis. |
| From the nervous system | Very often | Drowsiness, dizziness. |
| Often | Dystonia, headache. |
| Infrequently | Tardive dyskinesia, parkinsonism, seizures, akathisia. |
| Very rare | Neuroleptic malignant syndrome. |
| Visual disturbances | Often | Accommodation and vision disorders. |
| Infrequently | Rotational eye movements. |
| Respiratory, thoracic and mediastinal disorders | Rare | Dyspnea. |
| Gastrointestinal tract | Very often | Dry mouth, hypersecretion of saliva. |
| Often | Constipation, dyspepsia, nausea. |
| Infrequently | Vomiting, diarrhea. |
| Renal and urinary disorders | Infrequently | Urination disorders, urinary retention. |
| Pregnancy, childbirth, perinatal period | Unknown | Withdrawal syndrome in newborns. |
| Skin and subcutaneous tissue disorders | Often | Hyperhidrosis. |
| Infrequently | Rash, itching, photosensitivity reactions, dermatitis. |
| Musculoskeletal disorders | Often | Myalgia. |
| Infrequently | Muscle rigidity. |
| From the endocrine system | Rare | Hyperprolactinemia. |
| Metabolic disorders | Often | Increased appetite, weight gain. |
| Infrequently | Decreased appetite, weight loss. |
| Rare | Hyperglycemia, impaired glucose tolerance. |
| From the vascular side | Infrequently | Arterial hypotension, hot flashes. |
| Very rare | Venous thromboembolism. |
| General disorders and administration site conditions | Often | Asthenia, fatigue. |
| On the part of the immune system | Rarely | Hypersensitivity, anaphylactic reaction. |
| Liver and biliary tract disorders | Infrequently | Abnormal liver function tests. |
| Very rare | Jaundice. |
| Reproductive system and breast disorders | Infrequently | Lack of ejaculation, erectile dysfunction. |
| Rare | Gynecomastia, galactorrhea, amenorrhea. |
| Mental disorders | Often | Insomnia, anxiety, nervousness, decreased libido. |
There have been rare reports of QT prolongation, ventricular arrhythmias – ventricular fibrillation, ventricular tachycardia, torsades de pointes and sudden death with the use of medicinal products belonging to the therapeutic class of antipsychotics, including chlorprothixene.
Cases of priapism, a persistent, usually painful erection of the penis, which may lead to erectile dysfunction, have been reported with the use of medicinal products belonging to the therapeutic class of antipsychotics; the frequency of cases is unknown (see section 4.4).
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
25 mg tablets – 100 tablets in a container; 1 container in a cardboard box.
50 mg tablets – 50 tablets in a container; 1 container in a cardboard box.
Vacation category
According to the recipe.
Producer
H. Lundbeck A/S / H. Lundbeck A/S.
Address
Ottiliavej 9, 2500 Valby, Denmark.
