Fluanxol^® (Tablets, Solution) 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 with pronounced antipsychotic, activating and anxiolytic action. The antipsychotic action of neuroleptics is associated with the blockade of dopamine receptors, but possibly also with the blockade of serotonin 5-HT receptors.

Fluanxol^® reduces the main symptoms of psychosis, including hallucinations, paranoid delusions and thought disorders.

The antipsychotic action of Fluanxol^® begins to manifest when the drug is administered orally at a dose of 3 mg/day; the intensity of the action increases with increasing dose both when taken orally and when administered intramuscularly.

Fluanxol^® has disinhibiting (anti-autistic and activating) properties, and also alleviates secondary mood disorders, which contributes to the activation of patients with depressive symptoms, increases their sociability and facilitates social adaptation.

In small and medium doses (up to 25 mg/day orally and up to 100 mg IM every 2 weeks) the drug does not have a sedative effect, however, in high doses it can cause a non-specific sedative effect.

When taken orally in small doses (up to 3 mg/day) the drug has an antidepressant effect.

Fluanxol^® solution for intramuscular injection, oily, is intended for depot injections, being a depot form of flupentixol. In this dosage form, the drug has a significantly longer duration of action than Fluanxol^® in tablet form, and allows for continuous antipsychotic therapy, which is especially important for the treatment of patients who do not comply with medical prescriptions. The use of Fluanxol^® in the form of a solution for intramuscular injection prevents frequent relapses associated with voluntary discontinuation of treatment by patients when taking the drug orally. Fluanxol^® injections can be administered at intervals of 2-4 weeks.

Pharmacokinetics

Absorption

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

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

Distribution

The apparent V_d is about 14.1 L/kg. Plasma protein binding is about 99%. With intramuscular injection of the injection solution, C_ss is reached after 3 months of using the drug.

Flupentixol and cis(Z)-Flupentixol slightly cross the placental barrier and are excreted in small amounts in breast milk.

Metabolism

Metabolites do not possess neuroleptic activity.

Excretion

With intramuscular injection of the injection solution, the serum concentration curve decreases exponentially with a T_1/2 of approximately 3 weeks, which reflects the rate of release of flupentixol from the depot.

The metabolites of flupentixol do not possess neuroleptic activity. They are excreted mainly in the feces and, partially, in the urine. T_1/2 is approximately 35 hours.

Pharmacokinetically, a dose of Fluanxol^® 40 mg administered intramuscularly once every 2 weeks is equivalent to a dose of Fluanxol^® 10 mg/day taken orally for 2 weeks.

Indications

For oral administration in doses up to 3 mg/day

• Mild to moderate depression with anxiety, asthenia and lack of initiative;
• Chronic neurotic disorders with anxiety, depression and apathy;
• Psychosomatic disorders with asthenic reactions.

For oral administration in doses of 3 mg/day and more

• Schizophrenia and schizophrenia-like psychoses with a predominance of hallucinatory symptoms, delusions, thought disorders, also accompanied by apathy, anergy, low mood and autism.

For intramuscular injection

• Schizophrenia and other psychotic conditions occurring with hallucinations, delusions and thought disorders, accompanied by apathy, anergy, low mood and autism.

ICD codes

Dosage Regimen

Tablets

The dose, method, regimen and duration of therapy are set individually depending on the indications, clinical situation, patient’s age, response to treatment and the dosage form used.

Solution

For oral administration in doses up to 3 mg/day

For mild to moderate depression with anxiety, asthenia and lack of initiative; chronic neurotic disorders with anxiety, depression and apathy; psychosomatic disorders with asthenic reactions the initial dose of the drug is 1 mg once/day in the morning or 500 mcg 2 times/day. If there is no satisfactory therapeutic effect after 1 week, the dose can be increased to 2 mg/day. A daily dose ranging from 2 mg to 3 mg should be divided into several doses. For elderly patients the recommended daily dose is 0.5-1.5 mg.

The therapeutic effect usually appears within 2-3 days. If no effect is observed within a week at the maximum dose of 3 mg/day, the drug should be discontinued.

For oral administration in doses of 3 mg/day and more

In the therapy of psychotic conditions the dose is set individually, depending on the patient’s condition. At the beginning of treatment, it is recommended to use the drug in low doses, which are then, depending on the patient’s response to treatment, quickly increased to achieve the optimal clinical effect.

The initial daily dose is 3-15 mg in 2-3 divided doses. If necessary, the dose can be increased to 20-30 mg/day. The maximum daily dose is 40 mg. For maintenance therapy, the drug is used in a dose of 5-20 mg/day.

For intramuscular injection

The solution for intramuscular injection is administered deep intramuscularly into the upper outer quadrant of the buttock. Injection into other muscles is not recommended. If the required volume of solution exceeds 2 ml, it is recommended to divide it into 2 parts and give 2 injections.

The drug in the form of a solution for intramuscular injection 20 mg/ml is usually administered at a dose of 20-40 mg (1-2 ml) every 2-4 weeks. Some patients may require higher doses or shorter intervals between injections. In case of exacerbation or acute relapse of the disease, administration of the drug at a dose of up to 400 mg at once with intervals of 2 or even 1 week may be required.

Transition from Fluanxol^® for oral administration to intramuscular injection

Daily dose (mg) of the drug for oral administration x 4 = single dose (mg) of the solution for intramuscular injection every 2 weeks.

At the same time, during the 1st week after the 1st injection, oral administration of the drug should be continued, but at a reduced dose.

Subsequent doses and intervals between injections are set according to the clinical effect. The maximum dose of Fluanxol^® for intramuscular injection is 400 mg at once with an interval between injections of 1 week.

Patients who are switched from therapy with depot forms of other drugs should receive Fluanxol^® taking into account the following ratios: 40 mg of flupentixol decanoate is equivalent to 25 mg of fluphenazine decanoate, 200 mg of zuclopenthixol decanoate or 50 mg of haloperidol decanoate.

Adverse Reactions

Nervous system disorders drowsiness, headache, tremor, akathisia, parkinsonism, hypokinesia, dystonia, speech disorders, depression, insomnia, nervousness, agitation; sometimes – dizziness, attention disturbances, extrapyramidal disorders (mainly muscle rigidity and hyperkinesis), dyskinesia, amnesia, seizure disorders, aggression, decreased libido, confusion; rarely – tardive dystonia.

It should be borne in mind that when using neuroleptics, including flupentixol, in rare cases, the development of NMS is possible. The main symptoms of NMS are: hyperthermia, muscle rigidity and impaired consciousness in combination with autonomic nervous system dysfunction (labile BP, tachycardia, increased sweating). If these symptoms appear, urgent withdrawal of the neuroleptic and the appointment of symptomatic and supportive therapy are necessary.

With long-term treatment with the drug, the development of tardive dyskinesia is possible. Antiparkinsonian drugs do not eliminate its symptoms and may worsen them. Dose reduction or, if possible, discontinuation of treatment is recommended.

For persistent akathisia, benzodiazepines or propranolol may be effective.

In the first few days after injection and in the early stages of treatment, motor disturbances may occur. In most cases, such effects are controlled by dose reduction and/or antiparkinsonian drugs. However, the routine use of antiparkinsonian agents for the prevention of side effects is not recommended.

Transient insomnia or anxiety may be observed, especially if patients have previously taken neuroleptics with a sedative effect.

Cardiovascular system disorders sometimes – orthostatic hypotension, tachycardia; in rare cases (as with the use of other neuroleptics) – QT interval prolongation, ventricular arrhythmia (ventricular fibrillation, ventricular tachycardia, development of torsades de pointes ventricular tachycardia paroxysms, sudden death).

Hematopoietic system disorders rarely – granulocytopenia, agranulocytosis (more likely between the 4th and 10th weeks of treatment), leukopenia, hemolytic anemia.

Visual disorders accommodation disturbance, clouding of the cornea and/or lens with possible visual impairment; sometimes – oculogyric crisis, accommodation paresis.

Digestive system disorders dry mouth, digestive disorders (including constipation, diarrhea, dyspepsia, nausea), increased salivation, dysphagia, vomiting, cholestatic jaundice (more likely between the 2nd and 4th weeks of treatment), decreased appetite; in isolated cases – minor transient changes in liver function test parameters.

Endocrine system disorders galactorrhea, gynecomastia, dysmenorrhea, impotence, decreased libido, increased appetite, weight gain, hot flashes, changes in carbohydrate metabolism.

Urinary system disorders sometimes – urinary retention, painful urination.

Musculoskeletal system disorders sometimes – arthralgia.

Reproductive system disorders sometimes – erectile dysfunction.

Allergic reactions sometimes – itching, skin rash, dermatitis, photosensitivity, increased sweating.

Local reactions rarely – erythema, edema, inflammation or abscess.

Other weakness, asthenia.

Contraindications

• Vascular collapse;
• Depression of consciousness of any origin (including that caused by alcohol, barbiturates or opioid analgesics);
• Coma;
• Childhood and adolescence under 18 years;
• Hypersensitivity to the components of the drug;
• Hypersensitivity to phenothiazines;
• Hereditary intolerance to galactose and/or fructose; lactase deficiency lapp; sucrase and isomaltase deficiency; glucose and galactose absorption disorder (when taking tablets).

With caution use in patients with organic brain diseases, seizure disorders, including epilepsy (as a result of lowering the seizure threshold, an increase in seizures is possible); with severe hepatic insufficiency; with hypokalemia, hypomagnesemia; with a history of cardiovascular diseases (risk of transient BP decrease), including with prolonged QT interval, bradycardia less than 50 beats/min, with a recent acute myocardial infarction, with uncompensated heart failure, with arrhythmia; with risk factors for stroke; with glaucoma (and predisposition to it); with peptic ulcer of the stomach and duodenum; with alcoholism (possible enhancement of the depressant effect on the CNS); with pheochromocytoma; with leukopenia; respiratory impairment associated with acute infectious diseases, bronchial asthma or pulmonary emphysema; with Parkinson’s disease (enhancement of extrapyramidal effects); with urinary retention, prostatic hyperplasia with clinical manifestations (risk of urinary retention); with Reye’s syndrome (increased risk of hepatotoxic action); during pregnancy, during lactation (breastfeeding).

It is not recommended to prescribe Fluanxol^® in doses up to 25 mg/day to patients in a state of psychomotor agitation, because the activating effect of Fluanxol^® in small doses (when taken orally up to 3 mg/day or when administered intramuscularly 10-20 mg once every 2 weeks) can lead to an exacerbation of this symptomatology.

Use in Pregnancy and Lactation

The use of Fluanxol^® during pregnancy and lactation (breastfeeding) is possible only in cases where the intended therapeutic benefit for the mother outweighs the potential risk to the fetus.

Newborns whose mothers took neuroleptics in the III trimester of pregnancy or during childbirth may show signs of intoxication, such as lethargy, tremor, excessive excitability. In addition, such newborns have a low Apgar score.

Breastfeeding is allowed during treatment with Fluanxol^® if it is deemed clinically necessary. In such cases, it is recommended to monitor the condition of the newborn, especially in the first 4 weeks after birth.

Use in Hepatic Impairment

The drug should be prescribed with caution to patients with hepatic insufficiency.

Pediatric Use

Contraindication: childhood and adolescence under 18 years.

Geriatric Use

For elderly patients the recommended daily dose for oral administration is 0.5-1.5 mg.

Special Precautions

In case of prior treatment with neuroleptics or tranquilizers with a sedative effect, their administration should be discontinued gradually.

During long-term therapy, especially with the use of Fluanxol^® in high doses, careful monitoring and periodic assessment of the patients’ condition is necessary in order to timely correct the maintenance dose.

In concomitant treatment of diabetes, the appointment of Fluanxol^® may require adjustment of the insulin dose.

Effect on ability to drive vehicles and operate machinery

During the treatment period, the patient should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms possible drowsiness, hyper- or hypothermia, extrapyramidal disorders, convulsions, shock, coma.

With simultaneous administration with drugs that affect cardiac activity, ECG changes, QT interval prolongation, ventricular arrhythmias, including torsades de pointes arrhythmia, cardiac arrest have been recorded.

Treatment symptomatic and supportive therapy is carried out. In case of oral administration of the drug, gastric lavage should be performed as soon as possible, intake of a sorbent is recommended. Measures should be taken to maintain the activity of the respiratory and cardiovascular systems. Epinephrine should not be used, as this may lead to a subsequent decrease in BP. Convulsions can be controlled with diazepam, and extrapyramidal symptoms with biperiden.

Drug Interactions

With simultaneous use, Fluanxol^® may enhance the sedative effect of ethanol, barbiturates and other agents that have a depressant effect on the CNS.

Fluanxol^® should not be used concomitantly with guanethidine and agents with a similar action, because neuroleptics may weaken their hypotensive action.

Tricyclic antidepressants and neuroleptics (including Fluanxol^®) mutually inhibit metabolism.

Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.

With simultaneous use, Fluanxol^® may reduce the effectiveness of levodopa and the action of adrenergic agents.

With simultaneous use of Fluanxol^® with metoclopramide and piperazine, the risk of developing extrapyramidal disorders increases.

Prolongation of the QT interval, characteristic of therapy with antipsychotic agents, may increase with the simultaneous administration of drugs that have the same effect, including class I A and III antiarrhythmics (quinidine, amiodarone, sotalol, dofetilide), some antipsychotic agents (thioridazine), some macrolide antibiotics (erythromycin) and quinolone antibiotics (gatifloxacin, moxifloxacin), some antihistamines (terfenadine, astemizole), cisapride, lithium preparations. Simultaneous administration of Fluanxol^® and the listed drugs should be avoided.

With simultaneous use with drugs that cause electrolyte disturbances (thiazide and thiazide-like diuretics) and drugs that can increase the concentration of flupentixol or flupentixol decanoate in blood plasma, an increase in the risk of QT interval prolongation and the occurrence of life-threatening arrhythmias is possible.

Pharmaceutical Interaction

Fluanxol^® in the form of a solution for intramuscular injection should not be mixed with depot forms based on sesame oil, as this may have a significant effect on the pharmacokinetics of the administered drugs.

Storage Conditions

List B. Tablets should be stored at a temperature not exceeding 30°C (86°F); shelf life – 3 years.

The oil solution for intramuscular administration should be stored in a light-protected place at a temperature not exceeding 25°C (77°F); shelf life – 4 years.

The drug should be stored out of the reach of children.

Dispensing Status

The drug is dispensed by prescription.

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.