Description
Pharmacological action of
The antipsychotic effect of antipsychotics is associated with blockade of dopamine receptors, but possibly blockade of 5 HT (5-hydroxytryptamine) receptors.
The antipsychotic effect of Fluanxole begins to appear even with a daily dose of 3 mg and its severity increases with increasing dose. Fluanxol has a pronounced anxiolytic effect. The drug has disinhibition (anti-autistic and activating) properties, promotes the activation of patients, increases their sociability and facilitates social adaptation.
In small and medium doses (up to 25 mg per day) Fluanxol does not have a sedative effect, however, when prescribing the drug in a dose of more than 25 mg / day. sedation may develop.
When taking small doses (up to 3 mg / day.) Fluanxol has an antidepressant effect.
Pharmacokinetics
Absorption
After oral administration of Cmax, flupentixol in plasma is reached after 3-6 hours. Bioavailability is about 40%.
After intramuscular administration of cis (Z) -fluupentixol, decanoate undergoes enzymatic cleavage into the active component of cis (Z) -flupentixol and decanoic acid. Serum Cmax cis (Z) -fluupentixol is reached by the end of the first week after injection.
Distribution of
The apparent Vd is about 14.1 l / kg. Plasma protein binding is about 99%. With intramuscular injection of a solution for injection, Css is achieved after 3 months of use of the drug.
Flupentixol and cis (Z) -flupentixol slightly penetrate the placental barrier, excreted in small amounts with breast milk.
Metabolism
Metabolites do not have antipsychotic activity.
Excretion of
With an intramuscular injection of the injection solution, the serum concentration curve decreases exponentially with a T1 / 2 of about 3 weeks, which reflects the rate of release of flupentixol from the depot.
Flupentixol metabolites do not have antipsychotic activity. They are excreted mainly with feces and, partially, with urine. T1 / 2 is approximately 35 hours.
Pharmacokinetically, a dose of Fluanxole 40 mg when administered intramuscularly once every 2 weeks is equivalent to a dose of Fluanxol 10 mg / day when taken orally for 2 weeks.
Indications
Schizophrenia and other psychotic conditions occurring with hallucinations, delusions and impaired thinking, accompanied by apathy, anergy, decreased mood and autism.
Contraindications
Inhibition CNS
acute alcohol intoxication
acute intoxication barbiturates
acute intoxication opioid analgesics
coma
pathological changes in blood
bone marrow suppression
pheochromocytoma
collapse
pregnancy
lactation (breastfeeding)
childhood
increased sensitivity to neuroleptic thioxanthene structure.
Patients in a state of agitation or hyperactivity should not be prescribed in insufficiently high doses (up to 3 mg).
Use during pregnancy and lactation
Use of Fluanxole during pregnancy and lactation (breastfeeding) is possible only if the intended benefit of the therapy for the mother outweighs the potential risk to the fetus.
In newborns whose mothers took antipsychotics in the third trimester of pregnancy or during childbirth, signs of intoxication can be observed, such as lethargy, tremor, excessive irritability. Moreover, such newborns have a low Apgar score.
During treatment with fluanxol, breastfeeding is allowed if clinically recognized as necessary. In such cases, it is recommended to monitor the condition of the newborn, especially in the first 4 weeks after birth.
Composition of
1 ml of solution for intramuscular injection contains:
active substance:
cis (Z) -flupentixol decanoate 20 mg,
excipients:
Dosage and administration
The solution for intramuscular injection is injected deeply intramuscularly into the upper outer quadrant of the buttock. Into other muscles is not recommended. If the required volume of the solution exceeds 2 ml, it is recommended to divide it into 2 parts and make 2 injections.
A preparation in the form of a solution for intramuscular injection of 20 mg / ml is usually administered at a dose of 20-40 mg (1-2 ml) every 2-4 weeks. Some patients may need higher doses or shorter intervals between injections. With an exacerbation or acute relapse of the disease, it may be necessary to administer the drug in a dose of up to 400 mg at a time at intervals of 2 or even 1 week.
Transition from Fluanksol for oral administration to intramuscular injection
Daily dose (mg) of the drug for oral administration x 4 = singlethe second dose (mg) of the solution for intramuscular administration every 2 weeks.
In this case, within 1 week after the 1st injection, you should continue to take the drug inside, but in a reduced dose.
Subsequent doses and intervals between injections are set according to the clinical effect. The maximum dose of Fluanxole for intramuscular administration is 400 mg at a time with an interval between injections of 1 week.
Patients who are being transferred from therapy to 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 zuclopentixol decanoate or 50 mg of haloperidol decanoate.
Side effects
The incidence of side effects and their severity are most pronounced at the beginning of treatment, decrease as therapy continues.
From the nervous system: drowsiness, dizziness, headache, tremor, akathisia, parkinsonism, hypokinesia, dystonia infrequently – impaired attention, extrapyramidal disorders (mainly muscle rigidity and hyperkinesis), dyskinesia, amnesia, convulsive disorders, tardive dystonia.
From the side of mental activity: insomnia, nervousness, agitation infrequently – decreased libido, depression, confusion.
From the cardiovascular system: infrequently – palpitations, orthostatic hypotension.
From the hemopoietic organs: rarely – granulocytopenia, agranulocytosis (more likely between 4 and 10 weeks of treatment), leukopenia, hemolytic anemia.
From the side of the organs of vision: violation of accommodation, clouding of the cornea and / or lens with possible visual impairment infrequently – oculogyric crisis.
From the digestive system: dry mouth, digestive disorders (including constipation, diarrhea, dyspepsia, nausea), increased salivation, vomiting, cholestatic jaundice (more likely between 2 and 4 weeks of treatment).
Metabolic and nutritional disorders: infrequently – decreased appetite, increased appetite.
From the respiratory system: infrequently – shortness of breath.
From the endocrine system: dysmenorrhea, gynecomastia, diabetes mellitus, decreased potency, changes in carbohydrate metabolism, hot flashes.
From the urinary system: infrequently – urinary retention, painful urination.
Allergic reactions: infrequently – itching, dermatitis, skin rash, photosensitivity, increased sweating.
Disorders of the musculoskeletal system and connective tissue: infrequently – arthralgia.
From the reproductive system: infrequently – erectile dysfunction, galactorrhea.
On the part of the body as a whole: weakness, asthenia infrequently – weight gain.
There is evidence of the development of malignant antipsychotic syndrome (ZNS). The main symptoms of ZNS are hyperthermia, muscle rigidity and impaired consciousness in combination with autonomic nervous system dysfunction (labile blood pressure, tachycardia, increased sweating). In addition to the immediate cessation of antipsychotic administration, the use of general supportive measures and symptomatic treatment is imperative.
Patients on long-term treatment may develop tardive dyskinesia. Antiparkinsonian drugs do not eliminate its symptoms and may exacerbate them. Dose reduction or, if possible, discontinuation of treatment is recommended.
With persistent akathisia, benzodiazepines or propranolol may be useful.
There are few reports of the development of minor transient changes in the performance of liver function tests.
When taking flupentixol, the following side effects were also reported when taking other antipsychotics: in rare cases, prolongation of the QT interval, ventricular (ventricular) arrhythmia – ventricular fibrillation, ventricular tachycardia, sudden death and the development of paroxysms of ventricular tachycardia (Torsade de Pointes).
Drug Interaction
Fluanxol can enhance the sedative effect of alcohol, the action of barbiturates and other CNS depressants.
Fluanxol should not be given together with guanetidine or similarly acting drugs because of the possible attenuation of the antihypertensive effect of these agents.
Concomitant use of neuroleptics and lithium increases the risk of neurotoxicity.
Tricyclic antidepressants and neuroleptics mutually inhibit each other’s metabolism.
Fluanxol can reduce the effect of levodopa and the action of adrenergic drugs, and the combination with metoclopramide and piperazine increases the risk of extrapyramidal disorders.
The increase in QT interval characteristic of antipsychotic therapy may be enhanced by concomitant administration of drugs, QT prolonging interval: antiarrhythmic drugs IA and III classes (quinidine, amiodarone, sotalol, dofetilide), some antipsychotics (thioridazine), some antibiotics-macrolides (erythromycin), and antibiotics quinolifaxine, ginolifaxine, , astemizole) as well as cisapride, lithium and other drugs that increase QT interval. Concomitant use of Fluanxol and the above drugs should be avoided.
Fluanxol should be used with caution at the same time as drugs that cause electrolyte abnormalities (thiazide and thiazide-like diuretics) and drugs that can increase the concentration of flupentixol in blood plasma due to a possible increase in the risk of prolongation of Q
Pharmaceutical Interaction
Fluanxol in the form of a solution for intramuscular injection should not be mixed with deposited sesame oil based forms, because this can have a significant effect on the pharmacokinetics of the drugs administered.
Overdose
Symptoms. Drowsiness, coma, extrapyramidal symptoms, convulsions, shock, hyperthermia / hypothermia.
Changes to the ECG, QT prolongation, and QT prolongation were reported with concomitant medication with cardiac function. development of paroxysms of ventricular tachycardia (Torsade de Pointes), cardiac arrest, ventricular arrhythmia.
Treatment. Symptomatic and supportive. Gastric lavage should be performed as soon as possible, activated carbon is recommended. Steps must be taken to maintain the activity of the respiratory and cardiovascular systems. Epinephrine (epinephrine) should not be used because this can lead to a subsequent decrease in blood pressure. Seizures can be stopped with diazepam and extrapyramidal symptoms with biperiden.
Storage conditions
At a temperature not exceeding 25C.
Shelf suitability
4 Year
Active ingredient
Flupentixol
Terms of delivery from pharmacies
Prescription
dosage form
dosage form
injection
