Flupentixol - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Neuroleptics

Included in the formulation

Fluansoxol

solution w / m

H. Lundbeck A / S Denmark

Fluansoxol

pills

H. Lundbeck A / S Denmark

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

N.05.A.F.01 Flupentixol

Pharmacodynamics:

Antipsychotic (neuroleptic) thioxanthene derivative.

It blocks central postsynaptic dopamine D2 -receptors in the mesolimbic and mesocortical system, which causes a pronounced antipsychotic effect.

Effectively eliminates the productive symptoms of psychosis, including delirium, hallucinations, impaired thinking, as well as negative symptoms of schizophrenia (5HT unit2A serotonin receptor), weakens secondary mood disorders, promotes activation of patients with depressive symptoms and lack of initiative, improves communicability and improves social adaptation.

A block of dopamine D2-receptor chemoreceptor trigger zone of the vomiting center determines the antiemetic effect. Oppression of dopamine D2receptors in the basal ganglia (nigrostriral zone) leads to drug parkinsonism (extrapyramidal disorders). Oppression of D2- and D5- Dopamine receptors in the tuberoinfundibular system cause hyperprolactinemia, hypothermia,increased appetite and obesity. Central alpha block2-adrenergic and H1-gistaminovyh receptors - a sedative effect. Peripheral alpha-adrenoblocking and H1-gistaminoblocking effects are manifested by lowering blood pressure and antiallergic effect.

It has anxiolytic, disinhibiting (anti-astatic and activating) and antidepressant action. Antipsychotic effect is manifested at a dose of 3 mg per day and increases with increasing dose; antidepressant effect - in doses up to 3 mg per day. In high doses (25 mg per day or more) can cause a nonspecific sedation.

Depot forms of flupentixol are used for long-term therapy, as well as for the prevention of relapses associated with arbitrary interruption of treatment by patients.

Pharmacokinetics:Bioavailability of flupentixol after oral administration is about 40%. The dosage forms for intramuscular administration (depot form) are subjected to enzymatic cleavage with isolation of the active component of cis- (Z) -flupentixol and decanoic acid. The maximum concentration at ingestion is reached in 3-6 hours, with the introduction of depot forms - by the end of the first week after the injection.Equilibrium concentration with oral administration in most patients is achieved in 7-10 days, with the introduction of depot forms - after 3 months. Theoretical volume of distribution averages 14.1 l / kg, binding to plasma proteins - about 99%. In high concentrations found in the liver, lungs, intestines and kidneys, in smaller concentrations - in the heart, spleen, brain and blood. In small amounts passes through the placental barrier and penetrates into breast milk (the ratio of the concentration of the substance in breast milk and plasma is 1: 3). Biotransformirue(sulfo-oxidation, N-dealkylatione and glucuronation) with the formation of inactive metabolites, which are excreted mainly through the intestine and partly by the kidneys (in a ratio of 4: 1). Half-life with oral intake is about 35 hours, and for depot forms - 3 weeks. The system clearance is 0.29 (± 0.13) l / min. The effect of violations of the liver and kidneys on the pharmacokinetics of flupentixol has not been investigated, however, based on predominantly extrarenal elimination, renal dysfunction should not significantly affect the pharmacokineticsical parameters, whereas with a severe violation of liver function, the elimination process can be slowed down.

Indications:

Tablets (at a dose of up to 3 mg): mild and moderate depression, combined with anxiety, asthenia and lack of initiative; chronic neurotic disorders with anxiety, depression and apathy; psychosomatic disorders with asthenic manifestations; acute and situationally caused anxiety disorders and emotional stress conditions, which do not require a sedative / hypnotic effect (especially if the patient is suspected of being at risk of abuse of tranquilizers).

Tablets (at a dose of 3 mg or more), drops (4-40 mg per day), depot form: psychotic states with a predominance of hallucinatory symptoms, paranoid delusions and mental disorders, accompanied by apathy, anergy and autism.

Drops (in a dose of 40-150 mg per day): acute and chronic psychoses resistant to therapy (including schizophrenia); alcohol abstinence syndrome.

ICD-10

V.F10-F19.F19.3 Mental and behavioral disorders, causing. at the same time. Ex. Several. drugs and uses. other psychoactive substances - withdrawal symptoms

V.F20-F29.F20 Schizophrenia

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F30-F39.F32 Depressive episode

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F45.3 Somatoform dysfunction of the autonomic nervous system

V.F60-F69.F60.0 Paranoid personality disorder

XVIII.R40-R46.R44.3 Other hallucinations

XVIII.R40-R46.R45.1 Anxiety and Excitement

XVIII.R40-R46.R45.3 Demoralization and apathy

XVIII.R40-R46.R45.7 Condition of emotional shock and stress, unspecified

XVIII.R40-R46.R46.4 Retardation and delayed reaction

XVIII.R50-R69.R53 Malaise and fatigue

Contraindications:HypersensitivityAcute intoxication with alcohol and other drugs, oppressive central nervous system (barbiturates, opioid analgesics), coma, malignant neuroleptic syndrome, history of central hyperthermia, state of excitation and hyperactivity, pathological changes in blood, bone marrow suppression, collapse, pheochromocytoma, pregnancy, lactation , children's age till 18 years.

Carefully:Convulsive syndrome; progressive liver disease; cardiovascular diseasesthat system (including arrhythmia, severe hypotension, orthostatic disorders of blood circulation regulation); lesions of the brain, including the trunk (Parkinson's disease); breathing disorders associated with acute infectious diseases, asthma, emphysema; glaucoma, including an occlusive, or predisposedgo to it; clinically pronounced prostatic hypertrophy (risk of urinary retention); violation of emptying the bladder to form residual urine; Stomach ulcer and duodenal ulceroh intestines (possibly worsening of the condition); Reye's syndrome (increased risk of hepatotoxicityth exposure); alcoholism (possibly increased oppression of the central nervous system); renal failure, prolactin-dependentth tumors, stenosis of the gastrointestinal tract.

Pregnancy and lactation:

Category FDA - C. Flupentixol and its active metabolite penetrate insignificantly through the placental barrier, in small concentrations are excreted in breast milk. It is not recommended to use during pregnancy and lactation (breastfeeding).

In pregnancy, the drug may be used if the expected effect of therapy exceeds the potential risk for the fetus (animal experiments have revealed a teratogenic and embryotoxic effect, studies in humans have not been conducted).

Dosing and Administration:Inside. Pills. Depression and anxiety disorders: the initial dose is 1 mg once a day in the morning or 0.5 mg 2 times a day, if necessary, after 1 week, the dose is increased to a maximum daily dose of 3 mg divided into 2-3 doses; in the absence of effect in a dose of 3 mg per day, therapy is canceled.Psychotic conditions: the initial dose - 5-15 mg per day in 2-3 doses, if necessary - up to 40 mg per day; Supporting - 5-20 mg once a day in the morning.

Drops. Psychotic conditions: 4-16 mg per day (1-4 drops per day) in 2-3 doses, if necessary - up to 40 mg per day (10 drops per day). Acute and chronic psychoses resistant to therapy: the dose is set individually; 40-150 mg 4 times a day at the beginning of therapy, then 1-3 times a day.

Intramuscularly, deep into the gluteus muscle. Depot forms: 20-200 mg every 2-4 weeks, with exacerbation - up to 400 mg every 1-2 weeks, followed by a gradual decrease in the dose to the maintenance dose - 20-200 mg every 2-4 weeks.

Transition from oral forms to depot forms is carried out according to the scheme: oral daily dose (mg) x 4 = single dose (mg) of the depot form intramuscularly once in 2 weeks; In the first week after the injection, oral administration should be continued in reduced doses.

Side effects:

From the side CNS and sensory organs: at a dose of less than 3 mg per day - insomnia, drowsiness, anxiety, extrapyramidal disorders, at higher doses - extrapyramidal disorders (akathisia, parkinsonism, tremor, hypokinesia), insomnia, fatigue, depression (for depot forms), anxiety, accommodation paresis , drowsiness,dizziness; In addition, dyskinesia is late and early, epileptiform seizures provoked, glaucoma attacks, dystonic reactions (especially in children and young people), late dystonia, dyskinesia caused by drug withdrawal, deposition of opaque substances in the lens and cornea, retinopathy, swelling of the nasal mucosa ; in isolated cases - malignant neuroleptic syndrome (hyperthermia, muscle rigidity, impaired consciousness, vegetative-vascular dystonia - lability of blood pressure, tachycardia, increased sweating) with possible fatal outcome.

From the side of cardio-vascular system: arterial hypotension (at a dose above 40 mg per day), hematopoiesis (agranulocytosis, etc.), thrombosis, conduction disorders of the heart, tachycardia, orthostatic disorders of blood circulation regulation.

From the side organs of the digestive tract: hypersalivation, nausea, dry mouth, constipation, diarrhea, paralytic intestinal obstruction, cholestasis, in some cases - jaundice, transient changes in liver tests.

From the side genitourinary system: delayed urination, menstrual irregularity, sexual disorders (decreased sexual potency).

From the side skin integument: change in skin coloration (more often in women, with long-term therapy in high doses), toxic and allergic skin reactions, photosensitization.

Other: increased body weight, increased appetite, decreased sweating, increased mammary glands (in women and men), unusual secretion of milk.

Overdose:

Symptoms: severe respiratory failure, palpitations, drowsiness, coma, extrapyramidal disorders, pupillary narrowing, convulsions, arterial hypotension, unusual agitation, fatigue or severe weakness, shock, hypo- or hyperthermia.

Treatment: Gastric lavage and sorbent administration, if flupenthixol was prescribed inside, monitoring of vital functions, symptomatic and supportive therapy. With convulsions - the introduction of diazepam, extrapyramidal disorders - biperiden.

Interaction:

Amiodarone, Astemizole, Gatifloxacin. The increase in the QT interval, characteristic for therapy with antipsychotic agents, can be enhanced by simultaneous use of drugs that extend the QT interval. Avoid simultaneous application of flupenthixola and gatifloxacin, flupenthixol and astemizole, flupenthixol and amiodarone.

Levodopa. Flupentixol can reduce the effect of levodopa.

Metoclopramide.The simultaneous use of flupenthixol with metoclopramide increases the risk of extrapyramidal disorders.

Moxifloxacin. The increase in the QT interval, characteristic for therapy with antipsychotic agents, can be enhanced by the simultaneous use of moxifloxacin, which prolongs the QT interval. Avoid simultaneous use of flupenthixol and moxifloxacin.

Piperazine adipate. The simultaneous use of flupenthixol with piperazine adipinate increases the risk of extrapyramidal disorders.

Sotalol, Terfenadine, Thioridazine, Quinidine, Cisapride, Erythromycin. The increase in the QT interval, characteristic for therapy with antipsychotic agents, can be enhanced by simultaneous use of drugs that extend the QT interval. Avoid simultaneous application of flupenthixol and sotalol, flupenthixol and terfenadine, flupenthixol and thioridazine, flupentixol and quinidine, flupenthixol and cisapride, flupentixol and erythromycin.

Ethanol. Flupentixol can enhance the sedative effect of alcohol.

Special instructions:

A fatal outcome is possible with flupenthixol together with antiarrhythmic agents. More than haloperidol, causes motor (extrapyramidal) disorders at the beginning of treatment.

Solution for injection (depot form) can not be mixed with other solutions for injection (except for clopixol-acuphase in the form of co-injection).

Impact on the ability to drive vehicles and manage mechanisms.

Although in most cases the drug does not cause sedation, it is necessary to consider the possibility of its influence on the ability to drive and other mechanisms.

When flupenthixol is used (especially at the beginning of treatment), avoidance of potentially hazardous activities should be avoided until an individual response is determined.

Instructions

Flupentixol (Flupentixolum)