Flupentixol-nativ (Tablets) Instructions for Use

ATC Code

N05AF01 (Flupentixol)

Active Substance

Flupentixol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic (neuroleptic) agent

Pharmacological Action

Antipsychotic agent (neuroleptic), a thioxanthene derivative. It has a pronounced antipsychotic effect, as well as activating, antidepressant, and anxiolytic effects. The manifestation of flupentixol’s effects depends on its dose.

It is believed that the antipsychotic effect of neuroleptics is due to the blockade of dopamine receptors in the CNS. Thioxanthene derivatives have a high affinity for dopamine D₁ and D₂ receptors.

Unlike flupentixol hydrochloride, Flupentixol decanoate is a depot form, its action persists for 2-4 weeks.

Pharmacokinetics

After oral administration, the C_max of flupentixol in plasma is reached in 3-6 hours. Bioavailability is about 40%.

Flupentixol and cis-(Z)-flupentixol decanoate slightly cross the placental barrier and are excreted in small amounts in breast milk. Metabolites do not have neuroleptic activity.

After intramuscular injection, flupentixol decanoate undergoes enzymatic cleavage into the active component cis-(Z)-Flupentixol and decanoic acid. The C_max of cis-(Z)-flupentixol in serum is reached by the end of the first week after injection.

When taken orally, the biological T_1/2 is approximately 35 hours.

Flupentixol is excreted as metabolites, mainly through the intestines and partially by the kidneys.

Indications

For use in doses up to 3 mg/day: mild to moderate depression accompanied by anxiety, asthenia, and lack of initiative; chronic neurotic disorders with anxiety, depression, and apathy. Psychosomatic disorders with asthenic manifestations.

For use in doses of 3 mg/day and more: schizophrenia and schizophrenia-like psychoses with a predominance of hallucinatory symptoms, delusions, and thought disorders, also accompanied by apathy, anergy, low mood, and autism (including maintenance therapy – in the appropriate dosage form).

ICD codes

Dosage Regimen

Establish the dose, frequency, and duration of therapy individually based on indication, clinical presentation, and patient response.

For mild to moderate depression and chronic neurotic disorders, initiate with a low dose of 1 mg once or twice daily.

Increase the dose gradually by 0.5 mg to 1 mg every three to four days as tolerated.

The usual therapeutic range for these conditions is 1 mg to 3 mg daily, administered in divided doses.

For schizophrenia and psychotic disorders, initiate therapy with a higher dose, typically 3 mg to 6 mg daily in divided doses.

Titrate the dose upward based on therapeutic response and tolerability.

The maximum recommended daily dose is 12 mg for oral therapy, though some severe cases may require up to 18 mg under strict supervision.

Administer the total daily dose in two or three divided doses, typically after meals to minimize gastrointestinal discomfort.

For maintenance therapy, use the lowest effective dose that controls symptoms.

Regularly re-evaluate the need for continued treatment.

In elderly or debilitated patients, initiate treatment with a reduced dose of 0.5 mg once or twice daily.

Increase the dose more cautiously in this population due to increased sensitivity to adverse effects.

Do not use in children and adolescents under 18 years of age.

Abruptly discontinuing therapy is not recommended; taper the dose gradually to avoid withdrawal symptoms.

Monitor patients for extrapyramidal symptoms, sedation, and cardiovascular parameters, especially during dose titration.

Adverse Reactions

From the hematopoietic system rarely – thrombocytopenia, neutropenia, granulocytopenia, agranulocytosis, leukopenia, hemolytic anemia.

From the immune system: rarely – hypersensitivity reactions, anaphylactic reactions.

From the endocrine system rarely – hyperprolactinemia, dysmenorrhea, diabetes mellitus, decreased potency, changes in carbohydrate metabolism.

From the metabolism often – increased appetite, increased body weight; infrequently – decreased appetite; rarely – hyperglycemia, impaired glucose tolerance.

From the psyche often – insomnia, depression, nervousness, agitation, decreased libido; infrequently – confusion; frequency unknown – suicidal thoughts, suicidal behavior.

From the nervous system very often — drowsiness, akathisia, hyperkinesis, hypokinesia; often – dizziness, headache, tremor, dystonia, impaired attention; infrequently – tardive dyskinesia, dyskinesia, parkinsonism, speech disorders, convulsions; very rarely – NMS.

From the organ of vision often – impaired accommodation, visual impairment; infrequently – involuntary eye movements.

From the cardiovascular system: often – tachycardia, palpitations; infrequently – arterial hypotension, “flushes”; rarely – prolongation of the QT interval on ECG, ventricular arrhythmias – fibrillation and tachycardia, sudden death and polymorphic ventricular tachycardia of the “torsades de pointes” type; very rarely – venous thromboembolism.

From the respiratory system often – dyspnea.

From the digestive system very often – dry mouth; often – constipation, diarrhea, dyspepsia, increased salivation, vomiting; infrequently – abdominal pain, nausea, flatulence.

From the liver and biliary tract infrequently – changes in laboratory parameters of liver function; very rarely jaundice.

From the skin and subcutaneous tissues often – itching, increased sweating; infrequently – dermatitis, skin rash, photosensitivity.

From the musculoskeletal system: often – myalgia; infrequently – muscle rigidity.

From the urinary system often – urinary retention, impaired urination.

From the reproductive system: infrequently erectile dysfunction, ejaculation disorders; rarely – gynecomastia, galactorrhea, amenorrhea.

General reactions often – asthenia, weakness.

Abrupt withdrawal of flupentixol may be accompanied by the occurrence of withdrawal reactions with symptoms such as nausea, vomiting, anorexia, diarrhea, rhinorrhea, increased sweating, myalgia, paresthesia, insomnia, nervousness, anxiety and agitation, dizziness, sensations of heat and cold, tremor. Symptoms usually begin within 1 – 4 days after withdrawal and decrease within 7-14 days.

Contraindications

Hypersensitivity to flupentixol and to neuroleptics of thioxanthene structure; vascular collapse, depression of consciousness of any origin (including caused by alcohol, barbiturates, or opioids), coma; children and adolescents under 18 years of age.

With caution

Organic brain diseases; mental retardation; seizure disorders; severe hepatic insufficiency; hypokalemia, hypomagnesemia and genetic predisposition to such conditions; history of cardiovascular diseases (risk of transient decrease in blood pressure), including prolongation of the QT interval, bradycardia <50 beats/min, recent acute myocardial infarction, decompensated heart failure, arrhythmia; presence of risk factors for stroke; opioid and alcohol dependence (CNS depression may be enhanced); pregnancy, breastfeeding period.

It is not recommended to use Flupentixol intramuscularly in patients in a state of psychomotor agitation, as this may lead to an exacerbation of this symptomatology.

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant.

Newborns exposed to antipsychotic agents (including Flupentixol) in the third trimester of pregnancy are at risk of developing adverse reactions, including extrapyramidal symptoms and/or manifestations of withdrawal syndrome, which may vary in severity and duration after delivery. During treatment with flupentixol, breastfeeding may be continued if deemed clinically necessary. Medical monitoring of the newborn’s condition is recommended, especially in the first 4 weeks after birth.

Use in Hepatic Impairment

Use with caution in case of impaired liver function.

Use in Renal Impairment

Use with caution in case of impaired renal function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Flupentixol should not be used in insufficiently high doses in patients in a state of agitation or hyperactivity – this may lead to a deterioration of the patient’s condition.

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide. This risk persists until significant remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be under constant supervision until their condition improves. There is evidence that the risk of suicide may increase in the early stages of recovery.

Other mental conditions for which Flupentixol is prescribed may also be associated with an increased risk of suicidal events. In addition, these conditions may be comorbid with a depressive episode. When treating patients with other mental disorders, the same precautions should be observed as when treating patients with a depressive episode.

Patients with a history of suicidal behavior or patients with a significant level of suicidal ideation prior to treatment are at greater risk of suicidal thoughts or suicide attempts, so they should be closely monitored during treatment.

Use with caution in patients with convulsive syndrome, chronic hepatitis, cardiovascular diseases.

If NMS develops, flupentixol should be discontinued immediately and urgent symptomatic therapy should be initiated.

In case of prior therapy with neuroleptics with sedative effect, their administration should be discontinued gradually.

With long-term use of flupentixol in increased doses, regular examination of the patient’s condition is necessary in order to switch to treatment using lower doses.

During treatment with flupentixol, antiparkinsonian agents should be prescribed only in the presence of appropriate indications and should not be used prophylactically.

Before starting and during treatment with flupentixol, it is necessary to determine the risk factors for the development of venous thromboembolism and take precautions.

Against the background of the use of flupentixol, changes in the concentration of insulin and glucose in the blood are possible, which may require correction of the doses of hypoglycemic drugs in patients with diabetes mellitus.

Flupentixol should not be used simultaneously with guanethidine and other agents with a similar mechanism of action.

Influence on the ability to drive vehicles and mechanisms

During treatment with flupentixol, it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use, Flupentixol enhances the effects of drugs that have a depressant effect on the CNS, ethanol; may potentiate the action of anesthetic agents.

With simultaneous use, a decrease and complete inhibition of the hypotensive effect of guanethidine and agents with a similar mechanism of action is possible.

With simultaneous use, a decrease in the effects of levodopa and adrenergic agents is possible.

With simultaneous use with lithium carbonate, the development of extrapyramidal disorders is possible; with metoclopramide, piperazine – the risk of developing extrapyramidal disorders increases.

Tricyclic antidepressants and neuroleptics mutually inhibit each other’s metabolism.

Concomitant use with metoclopramide and piperazine increases the risk of developing extrapyramidal disorders.

QT interval prolongation, characteristic of antipsychotic therapy, may be enhanced by the simultaneous use of drugs that prolong the QT interval: class IA and III antiarrhythmic drugs (quinidine, amiodarone, sotalol, dofetilide), some antipsychotic agents (thioridazine), some macrolide antibiotics (erythromycin) and quinolone antibiotics (gatifloxacin, moxifloxacin), some antihistamines (terfenadine, astemizole), as well as cisapride, lithium and other drugs that increase the QT interval.

With simultaneous use of thiazide and thiazide-like diuretics and drugs that can increase the concentration of flupentixol in plasma, the risk of QT interval prolongation and life-threatening arrhythmias increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.