Flyuanksol

General characteristics. Structure:

Active ingredient: 20 mg or 100 mg цис (Z) - a flupentiksola of a dekanoat (in 1 ml of solution of 20 mg/ml - 20 mg, 100 mg/ml - 100 mg).

Excipients: triglycerides of an average chain.

Flyuanksol is antipsychotic means of group of thioxanthenes. Flyuanksol solution for intramuscular introduction (oil) is intended for depot injections, being the deposited form of a flupentiksol.

Pharmacological properties:

Pharmacodynamics. Flyuanksol possesses the expressed antipsychotic, activating and anxiolytic action. Antipsychotic action of neuroleptics is connected with blockade of dopamine receptors, but, perhaps, and blockade of 5 HT (5-gidroksitriptaminovy) receptors.

Flyuanksol is shown for treatment of patients with chronic psychoses. It reduces the main symptoms of psychosis such as hallucinations, nonsense and disturbances of thinking. Antipsychotic action amplifies with increase in a dose.

In small and medium doses (to 100 mg of 1 times in 2 weeks) Flyuanksol does not show sedative action which can develop when using drug in higher doses. Flyuanksol renders rastormazhivayushchy (anti-autistic and activating) action, and also weakens secondary frustration of mood that promotes activation of patients with depressive symptomatology, increases their skill to communicate and facilitates social adaptation.

Flyuanksol in this dosage form has considerably the big duration of action and allows to carry out continuous antipsychotic therapy that is especially important for treatment of the patients who are not carrying out medical appointments. Thus, Flyuanksol prevents the frequent recurrence connected with any interruption by patients of reception of peroral medicines. Flyuanksol's injections can be carried out bucketed in 2-4 weeks.

Pharmacokinetics. After an injection цис (Z) - the flupentiksola деканоат is exposed to zymolysis on active component цис (Z) - флупентиксол and decanoic acid.

The seeming volume of distribution (Vd) β makes about 14,1 l/kg. Linkng with proteins of a blood plasma about 99%. The maximum concentration цис (Z) - a flupentiksola in blood serum is reached by the end of the first week after introduction. Concentration in serum decreases exponential with the elimination half-life equal to about 3 weeks that reflects the speed of release of drug from depot; equilibrium concentration is reached approximately in 3 months of administration of drug.

Tsis (Z) - флупентиксол slightly gets through a placental barrier and in small amounts is allocated with breast milk. Metabolites have no antipsychotic activity; are allocated, generally with a stake and, partially, with urine. The elimination half-life makes about 35 hours.

Pharmacokinetically the dose of Flyuanksol entered intramusculary in a dose of 40 mg of 1 times in 2 weeks is equivalent to daily reception of Flyuanksol inside in a dose of 10 mg/days within 2 weeks.

Indications to use:

The schizophrenia and other psychotic states proceeding with hallucinations, nonsense and disturbances of thinking, which are followed by apathy, an anergy, a depression and autism.

Route of administration and doses:

Flyuanksol is entered deeply intramusculary into an upper outside quadrant of a rump. It is not recommended to enter into other muscles. If the necessary volume of solution exceeds 2 ml, it is recommended to divide it into two parts and to make two injections.

Flyuanksol of 20 mg/ml:
At the supporting treatment the range of dosages usually makes 20-40 mg (1-2 ml) each 2-4 weeks. Higher doses or shorter intervals between injections can be necessary for some patients. At an aggravation or an acute recurrence of a disease administration of drug in a dose up to 400 in one step bucketed mg in 2 can be required or even 1 week.

Flyuanksol of 100 mg/ml:
Range of dosages usually makes 50 mg (0,5 ml) each 4 weeks - 300 mg (3 ml) each 2 weeks. The dose to 400 mg (4 ml) a week can be required by some patients. After stopping of acute symptomatology gradual decrease in a dosage to a maintenance dose is made - usually to 20-200 mg there are each 2-4 weeks.

Upon transition from treatment by peroral forms of Flyuanksol on the supporting treatment by Flyuanksol entered intramusculary it is necessary to be guided by the following scheme: the daily dose of Flyuanksol in tablets in mg increased on 4 = Flyuanksol's dose in mg for intramuscular injection introduction at an interval of 2 weeks.

At the same time within the first week after the first injection it is necessary to continue oral administration of Flyuanksol, but in the reduced dose. Patients who are transferred from therapy of depot by forms of other drugs have to receive a dose in the ratio: 40 mg of a flupentiksol of a dekanoat are equivalent to 25 mg of Fluphenazin of a dekanoat, 200 mg of a zuklopentiksol of a dekanoat or 50 mg of a haloperidol of a dekanoat. The subsequent doses and intervals between injections have to be established according to clinical effect. The maximum dose of Flyuanksol entered intramusculary makes 400 mg in one step with an interval between injections of 1 week.

Features of use:

At the accompanying treatment of a diabetes mellitus Flyuanksol's appointment can demand insulin dose adjustment.

If earlier the patient was treated by neuroleptics or tranquilizers with sedative action, then their reception should be stopped gradually.

At long therapy, especially with use of high doses of Flyuanksol, it is necessary to carry out careful control and periodic assessment of a condition of patients.

During pregnancy Flyuanksol it is necessary to apply, only if the estimated advantage for mother exceeds potential risk for a fruit.

At newborns whose mothers accepted neuroleptics in the last trimester of pregnancy or at the time of delivery, symptoms of intoxication, such as lethargy, tremor and hyperexcitability can be observed. Besides, at such newborns the low point on a scale Apgar is noted.

During treatment by Flyuanksol feeding is allowed by a breast if it is recognized as clinically necessary. Nevertheless, it is recommended to watch a condition of the newborn, especially in the first 4 weeks after the birth.

During treatment it is necessary to refrain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of emergence of side effects and their weight are most expressed in an initiation of treatment, decrease in process of therapy continuation.
- From a nervous system: extrapyramidal frustration, parkinsonism, tremor, akathisia, dystonia, dyskinesia, alalias; infrequently - dizziness, is rare - late dystonia.
- From mental activity: depression, sleeplessness, agitation; infrequently - aggression.
- From cardiovascular system: orthostatic hypotension, tachycardia.
- From bodies of a hemopoiesis: seldom - a granulocytopenia, an agranulocytosis (is more probable between 4 and 10 weeks of treatment), a leukopenia, hemolitic anemia.
- From organs of sight: okulogirny crisis, opacification of a cornea and/or crystalline lens with a possible vision disorder, accommodation paresis; infrequently - accommodation disturbance.
- From the alimentary system: the increased salivation, a dysphagy (dysphagia), cholestatic jaundice (is more probable between 2 and 4 weeks of treatment); infrequently - a lock.
- Disturbances of metabolism and frustration of food: infrequently - a loss of appetite.
- From endocrine system: a galactorrhoea, a gynecomastia, a dysmenorrhea, impotence, decrease in a libido, increase in appetite, increase in body weight, the increased sweating, inflows, change of carbohydrate metabolism.
- From an urinary system: ischuria.
- From an organism in general: weakness, adynamy.
- Allergic reactions: infrequently - skin rash, dermatitis, a photosensitization.
- Local reactions: seldom - an erythema, hypostasis, an inflammation or abscess.

There are data on development of the malignant antipsychotic syndrome (MAS). The main symptoms of ZNS are the hyperthermia, muscular rigidity and disturbance of consciousness in combination with dysfunction of the autonomic nervous system (labile arterial pressure, tachycardia, the increased sweating). Except the immediate termination of reception of neuroleptics use of the general supporting measures and a symptomatic treatment is extremely necessary.

There can be motility disturbances, especially in the first few days after an injection and at early stages of treatment. In most cases these side effects are controlled by a dose decline and/or antiparkinsonichesky drugs. However routine use of antiparkinsonichesky means for prevention of side effects is not recommended.

Late dyskinesia can sometimes occur at the patients receiving a long course of treatment. Antiparkinsonichesky drugs do not reduce its manifestation, and are even capable to aggravate a state. The dose decline or, whenever possible, the treatment termination is recommended.

At a persistent akathisia there can be useful benzodiazepines or propranolol.

Sleeplessness (tranzitorny) and feeling of alarm, especially can be observed if patients accepted the neuroleptics possessing sedation earlier.

There are single messages on development of minor passing changes of indicators of functional hepatic trials.

At reception of a flupentiksol the following side effects arising at reception and other neuroleptics were also registered: in rare instances lengthening of an interval of QT, ventrikulyarny (ventricular) arrhythmia - fibrillation of ventricles, ventricular tachycardia, development of paroxysms of ventricular tachycardia (Torsade de Pointes) and sudden death.

Interaction with other medicines:

Flyuanksol can strengthen sedative effect of alcohol, action of barbiturates and other oppressing TsNS of substances.

Flyuanksol it is not necessary to appoint together with guanetidiny or similarly operating drugs because of possible weakening of hypotensive action of these means.

Simultaneous use of neuroleptics and lithium increases risk of a neurotoxicity.

Tricyclic antidepressants and neuroleptics mutually inhibit metabolism of each other.

Flyuanksol can reduce effect of a levodopa and effect of adrenergic drugs, and the combination with Metoclopramidum and piperazin increases risk of development of extrapyramidal disturbances.

The increase in QT of an interval characteristic of therapy by antipsychotic means, can be strengthened at a concomitant use of the drugs extending QT an interval: antiarrhytmic IA and III medicines of classes (quinidine, Amiodaronum, соталол, дофетилид), some antipsychotic means (thioridazine), some antibiotics macroleads (erythromycin) and antibiotics of a hinolonovy row (гатифлоксацин, moxifloxacin), some antihistamines (терфенадин, астемизол), and also a tsizaprida, lithium and other medicines increasing QT an interval. It is necessary to avoid a concomitant use of Flyuanksol and the drugs stated above.

Flyuanksol it is necessary to appoint with care along with the drugs causing electrolytic disturbances (thiazide and tiazidopodobny diuretics) and the drugs capable to increase concentration of a flupentiksol of a dekanoat in a blood plasma, because of possible increase in risk of lengthening of QT of an interval and developing of life-threatening arrhythmias.

Flyuanksol should not mix up with the deposited forms on the basis of sesame oil as it can exert considerable impact on pharmacokinetics of the administered drugs.

Contraindications:

Hypersensitivity to a flupentiksol or any of excipients (including the known hypersensitivity to fenotiazina).

Vascular collapse, oppression of consciousness of any origin (including caused by alcohol intake, barbiturates or opiates), a coma. Children's age (up to 18 years).

With care: organic diseases of a brain, convulsive frustration, a heavy liver failure, a hypopotassemia, a hypomagnesiemia, cardiovascular diseases in the anamnesis (risk of a tranzitorny lowering of arterial pressure), including lengthening of QT of an interval, bradycardia <50 beats per minute, recently postponed acute myocardial infarction, unindemnifiable heart failure, arrhythmia; existence of risk factors of development of a stroke, glaucoma (and predisposition to it), a peptic ulcer of a stomach and duodenum, alcoholism (oppression of TsNS can amplify); pheochromocytoma, leukopenia; the breath disturbance connected with acute infectious diseases, bronchial asthma or emphysema of lungs; Parkinson's disease (strengthening of extrapyramidal effects), an ischuria, a prostate hyperplasia with clinical manifestations (risk of an ischuria), a syndrome to Reja (increase in risk of development of a hepatotoxic action), epilepsy (as a result of decrease in a convulsive threshold increase of attacks is possible); pregnancy, breastfeeding period.

It is not recommended to appoint to patients in a condition of psychomotor excitement since the activating Flyuanksol's action in small doses (10-20 mg of 1 times in 2 weeks) can lead to an aggravation of this symptomatology.

Overdose:

Symptoms. Drowsiness, coma, extrapyramidal symptoms, spasms, shock, hyperthermia/hypothermia. At a concomitant use with the drugs exerting impact on cordial activity changes on an ECG, lengthening of an interval of QT, development of paroxysms of ventricular tachycardia (Torsade de Pointes), a cardiac standstill, ventrikulyarny arrhythmia were registered.

Treatment. Symptomatic and supporting. The measures directed to maintenance of activity of respiratory and cardiovascular systems have to be taken. It is not necessary to use Epinephrinum (adrenaline) since it can lead to the subsequent lowering of arterial pressure. Spasms can be stopped diazepam, and extrapyramidal symptoms Biperidinum.

Storage conditions:

List B. In the place protected from light at a temperature not above 25 °C. To store in places, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for intramuscular introduction (oil), 20 mg/ml, 100 mg/ml. Epakovka: On 1 ml in an ampoule from colourless glass of type 1 (Evr. Pharm.). 1 or 10 ampoules with the application instruction in a cardboard pack with perforated control of the first opening (a uvula for opening) on the substrate from a cardboard pasted to a pack bottom. The red point specifying the place of a break is applied on an ampoule.