Fluanxol oil solution for injection 20 mg/ml ampoule 1 ml №10

Flyuksol rr d / in / m enter. oil 20mg / ml 1 ml №10.

Clinico-pharmacological group

Antipsychotic drug (neuroleptic)

Mechanism of action

Antipsychotic agent (neuroleptic), a derivative of thioxanthene with a pronounced antipsychotic, activating and anxiolytic action. The antipsychotic action of neuroleptics is associated with the blockade of dopamine receptors, but perhaps also with the blockade of serotonin 5-HT receptors.

Fluanxol reduces the main symptoms of psychosis, incl. hallucinations, paranoid delusions and thinking disorders.

The antipsychotic effect of Fluanxol begins to manifest when the drug is used orally at a dose of 3 mg / day; the intensity of the action increases with increasing dose as with ingestion and with i / m administration.

Fluanxol has disinhibiting (anti-antacistic and activating) properties, as well as weakens secondary mood disorders, which activates patients with depressive symptoms, increases their communicability and facilitates social adaptation.

In small and medium doses (up to 25 mg / day when taken orally and up to 100 mg intramuscularly 1 time every 2 weeks), the drug does not have a sedative effect, but in high doses it can cause a nonspecific sedation.

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

Fluanxol solution for i / m injection of oil is intended for depot injection, being the deposited form of flupentixol. In this dosage form, the drug has a significantly longer duration of action than Fluanxol in the form of tablets, and allows continuous antipsychotic therapy, which is especially important for the treatment of patients who do not follow medical prescriptions. The use of Fluanxol in the form of a solution for i / m administration prevents frequent recurrences associated with the voluntary interruption of treatment by patients while taking the drug inside. Fluanksola injections can be performed at intervals of 2-4 weeks.

Pharmacokinetics

Suction

After ingestion C_max flupentixol in plasma is reached after 3-6 hours. Bioavailability is about 40%.

After i / m administration of cis (Z) -flupentixol, decanoate is subjected to enzymatic cleavage into the active component of cis (Z) -flupentixol and decanoic acid. C_max Serum cis (Z) -flupentixol is reached by the end of the first week after injection.

Distribution

Seeming v_d is about 14.1 l / kg. Plasma protein binding is about 99%. With the / m injection solution for injection C_ss is achieved after 3 months of use of the drug.

Flupentiksol and cis (Z) -flupentixol slightly penetrate the placental barrier, in small quantities are excreted in breast milk.

Metabolism

Metabolites do not possess neuroleptic activity.

Removal

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

Metabolites flupentiksola not possess antipsychotic activity. Excreted mainly in the feces and, in part, with the urine. T_1/2 is approximately 35 h.

Pharmacokinetic dose Fluanksola 40 mg with the / m administration of 1 every 2 weeks is equivalent to the dose of Fluanxol 10 mg / day when taken orally for 2 weeks.

Indications for use of the drug

For oral administration in a dose of 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 a dose of 3 mg / day or more

- schizophrenia and schizophrenia-like psychosis with a predominance of hallucinatory symptoms, delusions, thinking disorders, also accompanied by apathy, anergy, decrease in mood and autism.

For i / m introduction

- schizophrenia and other psychotic states, occurring with hallucinations, delusions and thinking disorders, accompanied by apathy, anergy, decreased mood and autism.

Dosage and administration

For oral administration in a dose of up to 3 mg / day

At 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 1 time / day in the morning or 500 mcg 2 times / day.In the absence of a satisfactory therapeutic effect after 1 week, the dose may be increased to 2 mg / day. The daily dose, comprising 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 occurs within 2-3 days. If at reception of the maximum dose of 3 mg / day the effect is not observed within a week, then the drug should be canceled.

For oral administration in a dose of 3 mg / day or more

During therapy psychotic states the dose is set individually, depending on the condition of the patient. At the beginning of treatment, it is recommended to use the drug in low doses, which then, depending on the patient's response to treatment, quickly increase to achieve the optimal clinical effect.

The initial daily dose is 3-15 mg in 2-3 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 i / m introduction

The solution for i / m injection is introduced deeply in a / m in the upper outer quadrant of the buttock. It is not recommended to inject into other muscles. If the required volume of the solution exceeds 2 ml, it is recommended to divide it into 2 parts and make 2 injections.

The drug in the form of a solution for i / m injection of 20 mg / ml is usually administered in a dose of 20-40 mg (1-2 ml) every 2-4 weeks. Some patients may need higher doses or shorter intervals between injections. At exacerbation or acute relapse of the disease It may be necessary to administer the drug in a dose of up to 400 mg at one time at intervals of 2 or even 1 week.

The transition from Fluanksola for oral administration to the / m introduction

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

At the same time, during the 1st week after the 1st injection, the drug should be continued inside, but in a reduced dose.

Subsequent doses and intervals between injections are set in accordance with the clinical effect. The maximum dose Fluanksola with the / m introduction is 400 mg simultaneously with an interval between injections in 1 week.

Patients who are transferred from therapy with depo-forms of other drugs should receive Fluanxol taking into account the following ratios: 40 mg of flupentixol decanoate is equivalent to 25 mg of flufenazine decanoate, 200 mg of suklopentyxol decanoate or 50 mg of Haloperidol decanoate.

Side effect

Nervous system: drowsiness, headache, tremor, akathisia, parkinsonism, hypokinesia, dystonia, speech disorders, depression, insomnia, nervousness, agitation; sometimes - dizziness, attention disorders, extrapyramidal disorders (mainly muscular rigidity and hyperkinesis), dyskinesia, amnesia, convulsive disorders, aggression, decreased libido, confusion; rarely - late dystonia.

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

With prolonged drug treatment may develop tardive dyskinesia. Anti-Parkinsonian drugs do not eliminate its symptoms and may aggravate them. A dose reduction or, if possible, discontinuation of treatment is recommended.

Benzodiazepines or propranolol may be effective in persisting actatisia.

In the first few days after the injection and in the early stages of treatment, motility disorders may occur. In most cases, such effects are controlled by dose reduction and / or anti-Parkinsonian drugs. However, the routine use of anti-parkinsonian drugs for the prevention of side effects is not recommended.

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

Since the cardiovascular system: sometimes - orthostatic hypotension, tachycardia; in rare cases (like when taking other antipsychotics) - prolongation of the QT interval, ventricular arrhythmia (ventricular fibrillation, ventricular tachycardia, development of paroxysmal ventricular tachycardia of the pirouette type, sudden death).

From the hemopoietic system: rarely - granulocytopenia, agranulocytosis (more likely between 4 and 10 weeks of treatment), leukopenia, hemolytic anemia.

On the part of the organ of vision: accommodation disturbance, corneal and / or lens opacity with possible visual impairment; sometimes - oculogy crisis, accommodation paresis.

From the digestive system: dry mouth, digestive disorders (including constipation, diarrhea, dyspepsia , nausea), increased salivation, dysphagia, vomiting, cholestatic jaundice (more likely between 2 and 4 weeks of treatment), loss of appetite; in isolated cases - slight transient changes in the functional liver function tests.

On the part of the endocrine system: galactorrhea, gynecomastia, dysmenorrhea, impotence, decreased libido, increased appetite, weight gain, hot flashes, altered carbohydrate metabolism.

From the urinary system: sometimes - urinary retention, painful urination.

From the musculoskeletal system: sometimes arthralgia.

From the reproductive system: sometimes erectile dysfunction.

Allergic reactions: sometimes - itching, skin rash, dermatitis, photosensitization, increased sweating.

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

Other: weakness, asthenia.

Contraindications to the use of the drug

- vascular collapse;

- depression of consciousness of any origin (including caused by alcohol intake, barbiturates or opioid analgesics);

- coma;

- children's and teenage age up to 18 years;

- hypersensitivity to the drug;

- hypersensitivity to phenothiazines;

- hereditary intolerance to galactose and / or fructose; lapp lactase deficiency; lack of sucrase and isomaltase; impaired absorption of glucose and galactose (while taking pills).

WITH caution use in patients with organic brain diseases, convulsive disorders, incl. with epilepsy (as a result of lowering the threshold of convulsive readiness, an increase in seizures is possible); with severe liver failure; with hypokalemia, hypomagnesemia; a history of cardiovascular diseases (risk of transient reduction in blood pressure), incl. with prolongation of the QT interval, bradycardia less than 50 beats / min, with recent acute myocardial infarction, with uncompensated heart failure , with arrhythmias; with risk factors for stroke; with glaucoma (and predisposition to it); with gastric ulcer and duodenal ulcer; with alcoholism (possibly increased inhibitory effect on the central nervous system); with pheochromocytoma; with leukopenia; respiratory failure associated with acute infectious diseases, bronchial asthma, or pulmonary emphysema; in Parkinson’s disease (enhanced 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 a dose of up to 25 mg / day to patients in a state of psychomotor agitation, since the activating effect of Fluanxol in small doses (when administered orally up to 3 mg / day or when i / m administration of 10-20 mg 1 time every 2 weeks) can lead to an exacerbation of these symptoms.

Use of the drug during pregnancy and lactation

Use of Fluanxol during pregnancy and lactation (breastfeeding) is possible only in cases where the intended benefit of therapy for the mother outweighs the potential risk to the fetus.

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

Breast-feeding is allowed during treatment with Fluanxol if this 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.

Application for violations of the liver

With caution, the drug is prescribed to patients with liver failure.

special instructions

In the case of prior treatment with neuroleptics or tranquilizers with a sedative effect, their intake should be stopped gradually.

With long-term therapy, especially with the use of Fluanxol in high doses, it is necessary to carefully monitor and periodically assess the condition of patients in order to timely adjust the maintenance dose.

With the concomitant treatment of diabetes, the prescription of Fluanxole may require correction of the insulin dose.

Influence on ability to drive motor transport and control mechanisms

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

Overdose

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

When taken simultaneously with drugs that affect cardiac activity, ECG changes, prolongation of the QT interval, ventricular arrhythmias, incl. arrhythmia type "pirouette", cardiac arrest.

Treatment: conduct symptomatic and supportive therapy. In the case of taking the drug inside it is necessary to wash the stomach as soon as possible, it is recommended to take a sorbent. Measures should be taken to support the activity of the respiratory and cardiovascular systems. Do not use epinephrine (adrenaline), because this can lead to a subsequent decrease in blood pressure. Spasms can be stopped by diazepam, and extrapyramidal symptoms - biperidenom.

Drug interaction

With simultaneous use Fluanxol may enhance the sedative effect of ethanol, barbiturates and other means that have a inhibitory effect on the central nervous system.

Fluanxol should not be used in conjunction with guanethidine and agents with a similar effect, becauseantipsychotics can weaken their hypotensive action.

Tricyclic antidepressants and neuroleptics (including Fluanksol) mutually inhibit metabolism.

The simultaneous use of neuroleptics and lithium increases the risk of neurotoxicity.

With simultaneous use Fluanxol can reduce the effectiveness of levodopa and the action of adrenergic agents.

With simultaneous use of Fluanxol with Metoclopramide and piperazine increases the risk of extrapyramidal disorders.

Prolongation of the QT interval, characteristic of antipsychotic therapy, may increase while taking drugs that have the same effect, including antiarrhythmics IA and III classes (quinidine, Amiodarone , sotalol, dofetilide), some antipsychotics (thioridazine), some macrolide antibiotics (erythromycin) and antibiotics of the quinolone series (gatifloxacin, moxifloxacin), some antihistamines (terfenadine, astemizole), cisapride, lithium preparations. It is necessary to avoid simultaneous administration of Fluanxol and the listed drugs.

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 the blood plasma, the risk of prolongation of the QT interval and the occurrence of life-threatening arrhythmias may increase.

Pharmaceutical Interaction

Fluanxol in the form of a solution for i / m injection should not be mixed with the deposited forms based on sesame oil, because this may have a significant effect on the pharmacokinetics of the drugs administered.

Terms and conditions of storage

List B. Tablets should be stored at a temperature not exceeding 30 ° C.

The solution for i / m injection of oil should be stored in a dark place at temperatures not above 25 ° C.

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