Moditenum of Depot

General characteristics. Structure:

Active ingredient: 25 mg of Fluphenazin of a dekanoat in 1 ml of solution.

Pharmacological properties:

Pharmacodynamics. Antipsychotic means (neuroleptic) of long action; treats group of polyvalent neuroleptics - has the expressed antipsychotic effect which is combined with some activating effect and also moderate sedative action, has antiemetic effect.

Antipsychotic action is caused by blockade dopamine D2 receptors of mesolimbic and mesocortical system. Sedative action (it is expressed moderately and it is observed at use in high doses) is caused by blockade of adrenoceptors of a reticular formation of a trunk of a brain; antiemetic action - blockade dopamine D2 receptors of a trigger zone of the emetic center; hypothermal action - blockade of dopamine receptors of a hypothalamus.

Effect of drug is usually shown in 24-72 hours after an injection, the antipsychotic effect is most expressed in terms from 48 to 96 watch after intramuscular introduction.

Pharmacokinetics. Fluphenazin in the form of ether of high-molecular, fatty acid and Solutio oleosa collects in fat depos and is slowly released.

After intramuscular introduction the maximum concentration in plasma is reached approximately in 24 hours. Fluphenazin contacts proteins of a blood plasma more than for 90%.

Fluphenazin passes through a blood-brain barrier, easily gets through a placental barrier and is not removed from an organism a hemodialysis.

Fluphenazin is actively and completely metabolized in a liver with the participation of enzymes of system of P450 cytochrome (including, CYP2D6 isoenzyme) and removed with urine and bile. Activity of metabolites of Fluphenazin is not studied.

Fluphenazin elimination half-life makes 7-10 days of a blood plasma.

Indications to use:

— long maintenance therapy of chronic forms of schizophrenia;

— prevention of exacerbations of schizophrenia.

Route of administration and doses:

The drug Moditenum of Depot is not intended for therapy courses less than 3 months. Initial dose: for most of patients the initial dose from 12,5 to 25 mg (0,5-1 ml) is recommended. The subsequent doses and intervals between introductions are defined in, dependences on the response to treatment.

Initial dose to the patients who were earlier not treated by drugs - derivatives of a fenotiazin, it is necessary to select administration of Fluphenazin of bystry action (Fluphenazin a hydrochloride).

Maintenance therapy. One injection allows to control schizophrenia symptoms within 4 weeks. During a maintenance therapy the effect of one dose at some patients remains up to 6 weeks.

The dose of the drug Moditenum of Depot should not exceed 100 mg. If introduction more than 50 mg of drug is required, it is necessary to raise each subsequent dose with care no more than on 12,5 mg.

Patients with the expressed excitement. Treatment should be begun with Fluphenazin of bystry action, such as Fluphenazin a hydrochloride for injections. After subsiding of acute manifestations it is possible to use 25 mg (1 ml) of Fluphenazin of a dekanoat of solution for intramuscular introduction.

The subsequent doses if necessary, are adjusted.

Patients with the increased risk of complications. At the known hypersensitivity to derivatives of a fenotiazin or frustration, предрасполагшопщх to adverse reactions, treatment should be begun carefully with hydrochloride Fluphenazin Inside or parenterally. After assessment of pharmacological effect and definition of an optimum dose it is possible to enter Fluphenazin деканоат for intramuscular introduction in an equivalent dose.

The subsequent dose adjustment is carried out depending on the response to treatment. There is no uniform scheme of transition from Fluphenazin of bystry action to administration of solution of Fluphenazin of a dekanoat. However it is known that the dose of 20 mg in days of Fluphenazin of a hydrochloride is equivalent to one injection of 1 ml (25 mg) of solution of Fluphenazin of a dekanoat each three weeks. Smaller doses - from 1/4 to 1/3 doses, appointed to young patients, and observation of reaction to treatment are required for most of elderly patients. If necessary the dose can be raised gradually.

Features of use:

Use at pregnancy and feeding by a breast. Use of drug at pregnancy and in the period of a lactation is contraindicated.

Use at abnormal liver functions. With care it is necessary to use drug at a liver failure.

Use at renal failures. With care it is necessary to use drug at a renal failure.

Use for children. It is contraindicated to children up to 12 years.

Use for elderly patients. With care it is necessary to use drug at elderly patients.

Special instructions. Due to the possible cross sensitivity it is necessary to appoint with care the drug Moditenum of Depot sick with allergic reactions to derivatives of a fenotiazin in the anamnesis.

At development of cholestatic jaundice as side reaction treatment by the drug Moditenum of Depot has to be stopped.

When carrying out surgeries by the patient accepting high doses of derivatives of a fenotiazin the sharp lowering of arterial pressure can be observed. Decrease in doses of anesthetics or neuroleptics at some patients at treatment can be required with the drug Moditenum of Depot; potentiation of effect of m-holinoblokatorov as Fluphenazin possesses m-holinoblokiruyushchim action is possible.

It is necessary to appoint with care the drug Moditenum of Depot at very hot weather or poisoning with phosphoric insecticides, to patients with convulsive attacks in the anamnesis (as against the background of treatment Fluphenazin described cases of big epileptic seizures), and also to patients at insufficiency of the mitral valve or, other disturbances of cardiovascular system or with a pheochromocytoma.

It is necessary to appoint with care drug at a breast cancer since as a result of induced by derivatives - the fenotiazina, secretions of prolactin increases risk to progress diseases and resistance to treatment by endocrine and cytostatic drugs.

Cases of development, venous thromboembolism were noted at reception of antipsychotic medicines. As the patients accepting antipsychotic medicines often have risk factors of development of a venous thromboembolism, it is necessary before and during treatment to estimate these factors and to take the appropriate preventive measures.

At appointment to patients with Parkinson's disease strengthening of extrapyramidal effects is possible.

The extrapyramidal symptoms arising in the form of side reactions as a rule, are reversible, but can be and resistant. The probability of emergence and expressiveness of such undesirable side reactions more depends on individual sensitivity, than on other factors, but the size of a dose and age of the patient matter. The patient has to be in advance warned about such manifestations and their reversibility. Usually for elimination of these undesirable phenomena; there is enough purpose of m-holinoblokatorov or antiparkinsonichesky drugs and/or a dose decline of drug.

Late dyskinesia. Expressiveness of it sindroma. the aggravation of symptoms caused by it can differ considerably at different patients. Late - dyskinesia is shown or during treatment at a dose decline, or after the therapy termination. Early detection of late dyskinesia is very important. For, detection of this syndrome, in an initial stage it is recommended to a periodic dose decline of a neuroleptic (if it is possible on a condition of the patient) and observation of the patient during this period. Such approach is extremely important; as treatment by neuroleptics can hide displays of late dyskinesia.

Malignant antipsychotic syndrome. At development of this side reaction it is necessary to stop immediately reception of the neuroleptics and other accepted drugs which are not influencing maintenance of vital signs and also the intensive symptomatic treatment, constant control of vital signs, and therapy of associated diseases is necessary.

Disturbances of cerebral circulation. Approximately 3-fold increase in risk of development of disturbances of cerebral circulation was observed at reception of some atypical neuroleptics at patients with dementia in the anamnesis. Increase in mortality of elderly patients with dementia in the anamnesis was observed during therapy by antipsychotic medicines. The risk degree and the reasons of this phenomenon are unknown.

The reason of this phenomenon is unknown, however it is impossible to exclude the increased risk of development of disturbances of cerebral circulation in other populations of patients or at reception of other neuroleptics. In this regard it is necessary to be careful at administration of drug Moditenum of Depot by patients with risk of development of disturbances of cerebral circulation:

Hypotension against the background of treatment by Fluphenazin meets seldom. At the same time, at patients with a pheochromocytoma, - the tssrebrovaskulyarny, renal and expressed heart failure (for example, at patients with insufficiency of the mitral valve) the gipotsgaiya against the background of administration of drug Moditenum of Depot develops more often; for these patients careful observation is necessary. At development of the expressed hypotension bystry intravenous administration of vasoconstrictive drugs is necessary. Best of all for this purpose Norepinephrinum is suitable for injections. Epinephrinum Should not be applied as derivatives of a fenotiazin pervert reaction to Epinephrinum owing to what a bigger decrease in the ABP is noted.

At development of diseases of a mucous membrane of an oral cavity, desenit throats or upper respiratory tract infections in combination with change of quantity of the leukocytes confirming hemopoiesis oppression, therapy by the drug Moditenum of Depot has to be cancelled, and necessary medical actions are immediately begun.

Patients with convulsive attacks in the anamnesis should appoint derivatives of a fenotiazin, including the drug Moditenum of Depot with care.

It is necessary to consider that antiemetic action of derivatives of a fenotiazin (including the drug Moditenum of Depot) can mask the vomiting connected with overdose of other medicines.

Sharp drug withdrawal: generally reception of derivatives of a fenotiazin. does not cause mental, dependences, however were noted cases of gastritis, nausea and vomiting, dizziness at sharp cancellation of high doses of derivatives of a fenotiazin. The specified symptoms decreased at the subsequent ambassador of cancellation reception of antiparkinsonichesky drugs within several weeks.

Drug contains sesame oil which in rare instances can cause heavy allergic reactions.

The benzyl alcohol which is contained in drug can cause heavy toxic and anaphylactoid reactions in children 12 years are more senior.

Alcohol intake during treatment of drugs is prohibited.

It is not necessary to store drug in the refrigerator as it will lead to sedimentation of the triglycerides which are a part of sesame oil. At emergence of a deposit drug should be heated to 37 °C, at the same time the deposit will be dissolved without loss of activity of active ingredient.

Influence on ability to driving of motor transport and to control of mechanisms. Drug makes strong impact on psychomotor reactions of the patient therefore during treatment it is forbidden to work with mechanisms or to drive the car.

Side effects:

From TsNS: extrapyramidal frustration, such as an extrapyramidal syndrome, an allotopia, dyskinesia, an akathisia, okulogirny crises, an opisthotonos and a hyperreflexia, late dyskinesia (the syndrome which is shown the involuntary choreoathetoid movements of language, face muscles, a mouth, lips or jaws (for example, protrusion of language, inflation of cheeks, a pulling of lips, the chewing movements) мьгшц a trunk and extremities).

Other neurologic frustration: the malignant antipsychotic syndrome (MAS) with a possible lethal outcome (a hyper pyrexia, muscle tension, changes of a mental state, vegetative frustration — fluctuation of frequency, pulse or arterial pressure, tachycardia, the increased sweating, disturbances of a cordial rhythm), ZNS can be also followed by development of a leukosis, fever, increase in activity of a kreatinfosfokinaza of LSFK), abnormal liver functions and an acute heart failure; drowsiness, confusion of consciousness, change of an encephalogram and cerebrospinal fluid protein content, brain hypostasis.

From the autonomic nervous system: orthostatic hypotension, fluctuations of arterial pressure, nausea, appetite loss, hypersalivation, a polyuria, perspiration, dryness in a mouth, a headache, a lock (as a rule, pass after a dose decline or drug withdrawal), hypotension. Also vision disorders, glaucoma, a bladder atony, impassability of intestines, tachycardia, a nose congestion are possible.

From cardiovascular system: lengthening of an interval of QT, ventricular arrhythmias, including fibrillation of ventricles, ventricular tachycardia, sudden death, cardiac standstill.

Metabolic and endocrine frustration: change of body weight, peripheral hypostases, a hyponatremia, a syndrome of disturbance of secretion of antidiuretic hormone, a pathological lactation, a gynecomastia, disturbance of a menstrual cycle, the false positive test for pregnancy, impotence at men, changes of a libido at women.

Allergic reactions: itch, erythema, urticaria, seborrhea, photosensitization, eczema and exfoliative dermatitis, anaphylactic reactions, bronchospasm, Quincke's disease, throat hypostasis.

From system of blood: a leukopenia, an agranulocytosis, thrombocytopenic and not thrombocytopenic - a purpura,
eosinophilia and pancytopenia.

From function of a liver: cholestatic jaundice, especially in the first months of therapy, change laboratory, function indicators baking clinical signs of hepatitis.

Others: convulsive attacks, at prolonged treatment - fever, vomiting, a volchanochnopodobny syndrome, changes an ECG, and also a xanthopathy, a phacoscotasmus and corneas, renal failures, a pigmental retinopathy, development of a closed-angle form of glaucoma, an irreversible diskinenziya, an asymptomatic form of pneumonia, a venous thrombembolia, including an embolism of a pulmonary artery and a deep vein thrombosis.

Interaction with other medicines:

Against the background of use of Fluphenazin effect of alcohol, drugs, ugayetayushchy TsNS (hypnotic drugs, sedatives) and strong analgetics amplifies. Simultaneous use with narcotic analgetics can cause hypotension, oppression of the TsNS function and breath.

Tricyclic antidepressants: derivatives of a fenotiazin break metabolism of tricyclic antidepressants. Concentration increase in serum and tricyclic antidepressants; and derivative fenotiazin. Also m-holinoblokiruyushchy effects, and also aritmogenny action can amplify or be prolonged sedative
- tricyclic antidepressants.

Lithium drugs at simultaneous use with Fluphenazin can raise a neurotoxicity.

APF inhibitors, thiazide diuretics: strengthening of hypotensive action is possible.

Other, antihypertensives: antigipretenzivny action of a guanetidin, clonidine and perhaps other anti-adrenergic means can decrease. The clonidine can reduce antipsychotic effect of fenotiazin.

Beta adrenoblockers: concentration of beta adrenoblockers and derivatives of a fenatiazin in a blood plasma can increase. At simultaneous use of beta adrenoblockers and derivatives of a fenotiazin the dose decline of drugs of both groups is recommended.

Metrizamid can cause convulsive attacks against the background of Fluphenazin use. It is recommended to cancel Fluphenazin in 48 hours prior to a miyelografiya and not to appoint it at least 24 hours after a miyelografiya.

Epinephrinum and other adrenomimetik: derivatives of a fenotiazin are their pharmacological antagonists owing to what development of the expressed hypotension is possible.

Levodopa: derivatives of a fenotiazin can reduce antiparkinsonichesky effect of drug.

M-holinoblokatory: at administration of Fluphenazin in combination with m-holinoblokatorami strengthening of blocking of cholinergic receptors, especially at elderly people is possible. M-holinoblokiruyushchiye effects are potentiated or prolonged. When using the drug Moditenum of Depot along with m-holinoblokatorami careful observation and selection of doses of drugs is necessary.

Anticonvulsants: Fluphenazin can reduce their anticonvulsant effect.

Hypoglycemic means: derivatives of a fenotiazin cause a diabetes mellitus decompensation. Cimetidinum can reduce concentration of derivatives of a fenotiazin in a blood plasma.

Antacids / Anti-diarrheal means can break Fluphenazin absorption.

Amphetamine / Anorexigenic means are pharmacological antagonists of Fluphenazin.

Substrates or inhibitors of an isoenzyme CYP2D6: Fluphenazin is metabolized by means of an isoenzyme of CYP2D6 and at the same time is inhibitor of this isoenzyme. Therefore concentration in plasma and effects of Fluphenazin can increase at reception of such drugs owing to what cardiotoxicity, the side reactions caused by m-holinoblokiruyushchim action or orthostatic hypotension is shown.

Contraindications:

— hypersensitivity to Fluphenazin or other components of drug;
— serious cardiovascular illness (dekompensirovaniy chronic circulatory unefficiency, arterial hypotension);
— the expressed oppression of the TsNS function and comas of any etiology; craniocereberal injuries, the progressing general diseases of a head and spinal cord;
— abnormal liver functions and systems of blood;
— pregnancy, lactation period;
— children's age up to 12 years.

With care:
— alcoholism (the increased predisposition to hepatotoxic reactions);
— allergic reactions to derivatives of a fenotiazin in the anamnesis;
— pathological changes of blood (hemopoiesis disturbance);
— breast cancer;
— zakrytougolpy glaucoma;
— a prostate hyperplasia with clinical manifestations;
— liver and/or renal failure;
— a peptic ulcer of a stomach and duodenum (in the period of an aggravation);
— the diseases which are followed by the increased risk of tromboembolic episodes;
— Parkinson's disease;
— epilepsy, convulsive attacks in the anamnesis;
— myxedema;
— the chronic diseases which are followed by breath disturbance (especially at children);
— syndrome to Reja (increase in risk of development of a gepatotoksichiost in children and teenagers);
- cachexia;
— vomiting;
— advanced age.

Overdose:

The expressed extrapyramidal frustration, hypotension, excessive, sedation, oppression of consciousness up to a coma with an areflexia. In such cases it is necessary to cancel medicine and to begin the supporting symptomatic treatment.

At development of the expressed hypotension immediate intravenous administration of vasoconstrictive medicines is necessary. Epinephrinum (adrenaline) should not be applied as at a concomitant use with derivatives of a fenotiazin the perverted reaction (a bigger decrease in the ABP) is noted. At development of the expressed extrapyramidal frustration antiparkinsonichesky funds for several weeks are appointed. Antiparkinsonichesky means have to be cancelled gradually to avoid a recurrence of extrapyramidal frustration.

The hemodialysis, peritoneal dialysis, exchange transfusions and artificial diuresis at poisoning with the drug Moditenum of Depot are inefficient.

Storage conditions:

To store at a temperature from 15 °C to 25 °C in the place protected from light. To store in the place, unavailable to children. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

1 ml - ampoules of dark glass (5) - planimetric strip packagings (1) - packs cardboard.
1 ml - ampoules of dark glass (50-600) - planimetric strip packagings (1) - packs cardboard.