Fluphenazine synonyms. Fluphenazine - drug use and possible side effects

1 ml of solution contains:

active substance: fluphenazine decanoate - 25 mg;

excipients: benzyl alcohol - 15 mg, sesame oil - up to 1 ml.

Transparent, yellowish oily liquid. May have a slight benzyl alcohol odor.

Fluphenazine is a piperazine derivative of phenothiazine. Fluphenazine decanoate provides a prolonged effect - from one to several weeks after a single injection; belongs to the group of polyvalent antipsychotics - it has a pronounced antipsychotic effect, combined with some activating effect, as well as a moderate sedative effect, has an antiemetic effect.

The antipsychotic effect is due to the blockade of dopamineD 2 -receptors of the mesolimbic and mesocortical system. The sedative effect (moderately expressed and observed when used in high doses) is due to the blockade of adrenergic receptors of the reticular formation of the brain stem; antiemetic action - blockade of dopamineD 2 -trigger zone receptors;hypothermic action - blockade of dopamine receptors of the hypothalamus.

The effect of the drug usually appears 24-72 hours after injection, the antipsychotic effect is most pronounced within 48 to 96 hours after intramuscular administration.

Suction

Fluphenazine decanoate is slowly absorbed at the site of administration and is hydrolyzed in plasma to active substance - fluphenazine.

Distribution

Fluphenazine, in the form of an ester of a high molecular weight fatty acid and an oil solution, accumulates in fat depots and is slowly released.

After intramuscular administration, the maximum plasma concentration is reached after approximately 24 hours. binds to blood plasma proteins by more than 90%.

Fluphenazine crosses the blood-brain barrier, easily penetrates the placental barrier and is not removed from the body by hemodialysis.

Metabolism

Fluphenazine is actively and completely metabolized in the liver with the participation of enzymes of the cytochrome P450 system (including the isoenzymeCYP2 D6) and is excreted in urine and bile. The activity of fluphenazine metabolites has not been studied.

Withdrawal

The plasma half-life of fluphenazine varies from 2.5 to 16 weeks. A stable level of the drug in blood plasma is achieved by injections at intervals of 2-4 weeks.

Long-term maintenance therapy of chronic forms of schizophrenia and other psychoses.

Prevention of exacerbations of schizophrenia.

-Hypersensitivity to fluphenazine decanoate or other components of the drug;

-simultaneous administration of epinephrine ("Overdose", "Interaction with other medicinal products", " special instructions");

-pronounced atherosclerosis of the vessels of the brain;

-severe cardiovascular disease (decompensated chronic insufficiency blood circulation, arterial hypotension);

-pronounced inhibition of the function of the central nervous system (CNS) and coma any etiology; traumatic brain injury, progressive systemic diseases of the brain and spinal cord;

-hepatic and / or renal failure;

-blood diseases;

-severe depression;

Pheochromocytoma;

-pregnancy, lactation period;

-children under 12 years of age (due to the lack of clinical data and the content of benzyl alcohol in the composition);

-simultaneous intake of alcohol ("Interaction with other medicinal products", "Special instructions").

-Alcohol dependence (increased predisposition to hepatotoxic reactions);

-impaired liver function;

-impaired renal function;

-a history of allergic reactions to phenothiazine derivatives;

-application in very hot weather;

-breast tumors;

-angle-closure glaucoma;

-severe myasthenia gravis(Myasthenia gravis);

-hyperplasia of the prostate with clinical manifestations;

-peptic ulcer and duodenum (during an exacerbation);

-diseases accompanied by an increased risk of thromboembolic complications;

-parkinson's disease;

-epilepsy, history of seizures;

-heart rhythm disturbances;

-hypothyroidism (myxedema) and hyperthyroidism (thyrotoxicosis);

-chronic diseases accompanied by respiratory failure (especially in children);

-reye's syndrome (increased risk of increased hepatotoxicity in adolescents);

Cachexia;

Vomiting;

-old age, especially in debilitated and / or at risk of developing hypothermia in patients;

-for patients with a history of cardiovascular disease, before the appointment of fluphenazine, it is necessary to make an ECG and correct the electrolyte balance.

Fluphenazine should be used with caution in patients who are exposed to organophosphate insecticides.

Pregnancy period: the safety of fluphenazine when used in pregnant patients has not been established, therefore, the drug should be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus.

Newborns whose mothers took antipsychotic drugs during the third trimester are at increased risk of developing extrapyramidal disorders and withdrawal. The duration and severity of symptoms can vary. Anxiety, hypertension, hypotension, tremors, drowsiness, and impaired breathing and / or feeding were observed.

Breastfeeding period: can stand out in breast milktherefore, taking fluphenazine during lactation is not recommended.

Fluphenazine decanoate is used as intramuscular injection... Since the drug is in the form of an oily solution, use a needle of at least 21G. The syringe and needle must be dry.

Fluphenazine is not intended for courses of therapy less than 3 months.

Adults

Patients who have not previously taken the drug in the form of decanoate (prolonged release)

Initial dose- deep intramuscular injection into the gluteal region, 0.5 ml (12.5 mg) for adult patients and 0.25 ml (6.25 mg) for elderly patients. Subsequent doses and intervals between injections are determined individually, depending on the response to treatment.

The onset of a pharmacological effect is usually noted between 24 and 72 hours after injection, and a marked decrease in psychotic symptoms is observed after 48-96 hours. Maximum flexibility must be observed in dosing to ensure an optimal therapeutic response with minimal side effects; in most patients it is possible to achieveoptimal maintenance therapy at dosages from 0.5 ml (12.5 mg) to 4.0 ml (100 mg) with the introduction of the drug every 2-5 weeks.

Supportive therapy

When using fluphenazine as a maintenance therapy, one injection provides control over the manifestations of schizophrenia within 4-6 weeks. It is necessary to select an individual dose with minimal side effects. In most patients, the desired pharmacological effect is achieved with the introduction of fluphenazine in doses from 0.5 ml (12.5 mg) to 4.0 ml (100 mg) with an interval of 2 to 5 weeks. A single dose of fluphenazine should not exceed 100 mg. If more than 50 mg of the drug is required, each subsequent dose should be increased under the supervision of a specialist, with caution, by no more than 12.5 mg, taking into account the individual variability of the response to treatment, which is also often characterized by a delayed effect. When therapy is discontinued, a relapse of the disease may appear only after several weeks or months.

Patients with severe agitation

Fluphenazine decanoate is prescribed after relief of excitement with other antipsychotics, including injections. After cupping acute manifestations you can enter 25 mg (1 ml) solution of fluphenazine decanoate; subsequent doses are adjusted if necessary.

Patients who have previously taken oral antipsychotics

There is no single scheme for switching to fluphenazine decanoate with other antipsychotics. Doses and transfer scheme should be selected by the doctor individually for each specific patient.

Patients who have previously taken in the form of decanoate (prolonged-release injections)

If a relapse of schizophrenia occurs after cessation of fluphenazine decanoate therapy, the same initial dose is used, but with a possible increase in the frequency of injections in the first weeks of treatment, until the desired effect is achieved

Elderly patients

Most elderly patients require smaller doses - from 1/4 to 1/3 of the dose given to younger patients. Elderly patients may exhibit increased sensitivity to the drug in the form of an increase in the incidence of extrapyramidal reactions, sedative and hypotensive effects (see sections "Side Effects" and "Special Instructions").

The patients childhood up to 12 years

Route of administration: intramuscularly.

Blood disorders and lymphatic system

Leukopenia, agranulocytosis, thrombocytopenic and non-thrombocytopenic purpura, eosinophilia and pancytopenia.

External violations immune system

Hypersensitivity reactions, anaphylactic reactions.

Metabolic and nutritional disorders

Change in body weight, peripheral edema, hyponatremia, syndrome of impaired secretion of antidiuretic hormone.

Mental disorders

Agitation, emotional excitement, insomnia.

Nervous system disorders

-acute extrapyramidal disorders such as extrapyramidal syndrome, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonus and hyperreflexia, tardive dyskinesia (a syndrome manifested by involuntary choreoathetoid movements of the tongue, muscles of the face, mouth, lips or jaw, puffing out stretching the lips, chewing movements) muscles of the trunk and limbs) usually develop within the first 24-48 hours;

-neuroleptic malignant syndrome (NMS) with a possible fatal outcome (hyperpyrexia, muscle stiffness, changes mental state, autonomic disorders - fluctuations in heart rate or blood pressure, tachycardia, increased sweating, cardiac arrhythmias), ZNS may also be accompanied by the development of leukocytosis, fever, increased creatine phosphokinase (CPK) activity, impaired liver function and acute cardiac renal failure, akinesia; drowsiness, confusion (sometimes turning into a stupor or coma), changes in the encephalogram and protein content in cerebrospinal fluid, cerebral edema;

-a parkinson-like condition may develop between the second and fifth days after injection, but often diminish with subsequent injections;

-tardive dyskinesia, the severity of this syndrome and the deterioration caused by it can vary significantly in different patients. Tardive dyskinesia occurs either during treatment with dose reduction or after discontinuation of therapy.

Early detection of tardive dyskinesia is very important. To detect this syndrome in initial stage it is recommended to periodically reduce the dose of the neuroleptic (if possible due to the patient's condition) and monitor the patient during this period. This approach is extremely important, since treatment with antipsychotics can mask the manifestations of tardive dyskinesia. Headache, epileptiform attacks, seizures.

In elderly patients, sedative and hypotensive effects may be expressed (see sections "Dosage and Administration" and "Special instructions").

Violations of the organ of vision

Blurred vision, glaucoma, clouding of the lens and cornea (with prolonged use of the drug).

Heart disorders

Span lengtheningQT, ventricular arrhythmias, including ventricular fibrillation, ventricular tachycardia, cardiac arrest, sudden death.

Vascular disorders

Hypotension, including orthostatic hypotension, fluctuations in blood pressure.

Frequency unknown: deep vein thrombosis, venous thromboembolism.

Respiratory and mediastinal disorders

Nasal congestion, embolism pulmonary artery, asymptomatic form of pneumonia, bronchospasm.

Frequency unknown: laryngeal edema (with prolonged use of the drug).

Gastrointestinal disorders

Nausea, constipation, dry mouth, bowel obstruction.

Liver and biliary tract disorders

Cholestatic jaundice, especially in the first months of therapy, hepatitis.

Skin and subcutaneous tissue disorders

Angioneurotic edema, urticaria, atypical skin pigmentation (with prolonged use of the drug), skin rash, photosensitivity reactions, exfoliative dermatitis, eczema.

Musculoskeletal and connective tissue

Very rare: systemic lupus erythematosus.

Kidney disorders and urinary tract

Difficulty urinating, urinary incontinence, atony bladder, renal failure.

Pregnancy, postpartum and perinatal conditions

Frequency not known: drug withdrawal syndrome in neonates.

Genital and breast disorders

Pathological lactation, gynecomastia, disorder menstrual cycle, false positive pregnancy test, impotence in men, libido changes in women.

Laboratory and instrumental data :

Changes in liver function parameters, rare transient increases in serum cholesterol have been reported in patients receiving oral administration.

Very rare: appearance antinuclear antibodies.

If any of those specified in the instructions side effects aggravated or you notice any other side effects not listed in the instructions,tell your doctor about it.

Severe extrapyramidal disorders, hypotension, excessive sedation, depression of consciousness up to coma with areflexia. In such cases, it is necessary to discontinue the medication and begin supportive symptomatic treatment.

With the development of severe hypotension, immediate intravenous administration vasoconstrictor drugs.

Epinephrine (adrenaline) not recommended to apply, since when taken simultaneously with phenothiazine derivatives, an even greater decrease in blood pressure is noted.

With the development of severe extrapyramidal disorders, prescribeantiparkinsonian drugs for a few weeks. Antiparkinsonian drugs should be withdrawn gradually to avoid recurrence of extrapyramidal disorders.

Hemodialysis, peritoneal dialysis, exchange transfusions and forced diuresis are ineffective in case of fluphenazine poisoning.

Fluphenazine enhances the deprimating effectsand alcohol, sleeping pills and sedatives; enhances actionanticoagulants , cardiodepressant effectquinidine,suction corticosteroids, digoxin, muscle relaxants.

Simultaneous use withnarcotic analgesics can cause hypotension, depression of the central nervous system and respiration.

Tricyclic antidepressants: phenothiazine derivatives violatemetabolism of tricyclic antidepressants. Serum concentrations of both tricyclic antidepressants and phenothiazine derivatives increase. The sedative and m-anticholinergic effects, as well as the arrhythmogenic effect of tricyclic antidepressants, can be enhanced or prolonged.

Lithium preparationswhen used simultaneously with fluphenazine, they can increase neurotoxicity.

Angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics: possibly an increase in the hypotensive effect (severe postural hypotension).

Other antihypertensive drugs: the antihypertensive effect of guanethidine, clonidine and possibly other antiadrenergic drugs may be reduced. may reduce the antipsychotic effect of phenothiazines.

Beta-blockers: the concentration of beta-blockers and phenathiazine derivatives in blood plasma may increase.

With the simultaneous use of beta-blockers and phenothiazine derivatives, it is recommended to reduce the dose of drugs of both groups.

Metrizamide can cause seizures with fluphenazine. It is recommended to withdraw it 48 hours before myelography and not prescribe it for at least 24 hours after myelography.

Eninephrine and other adrenergic agonists : phenothiazine derivatives are their pharmacological antagonists, as a result of which severe hypotension may develop.

Levodopa: derivatives of phenothiazine can reduce the antiparkinsonian effect of the drug.

M-anticholinergics: when fluphenazine is administered in combination with m-anticholinergics may increase the blocking of cholinergic receptors, especially in the elderly. M-anticholinergic effects are potentiated or prolonged.

When using the drug simultaneously with m-anticholinergics, careful observation and selection of doses of drugs is necessary.

Anticonvulsants: fluphenazine can reduce themanticonvulsant effect.

Barbiturates: induce the metabolism of phenothiazines. Simultaneousthe use of barbiturates with phenothiazines can lead to a decrease in serum levels of both drugs.

Fluphenazine may prolong the intervalQT, which can increase the risk of developing ventricular arrhythmias such as "pirouette", which are potentially dangerous (risk of "sudden death"). Span lengtheningQTespecially worse in the presence of bradycardia, hypokalemia and congenital or acquired lengthening of the intervalQT.

Sharing drugs that lengthen the intervalQTand fluphenazine is contraindicated. Examples are certain antiarrhythmic drugs, such as classI A (including disopyramide and) and class III (including and), tricyclic antidepressants (including), certain tetracyclic antidepressants (such as), certain antipsychotic drugs (including phenothiazides and pimozide), certain antihistamines (including terfenadine, lithium, quinine, pentamidine, and sporfloxacin).

Inhibitors reverse capture serotonin: inhibit the metabolism of phenothiazines.

Hypoglycemic agents: phenothiazine derivatives causedecompensation of diabetes mellitus.

Cimetidine: may reduce the concentration of phenothiazine derivatives in plasmablood.

Antacids / antidiarrheals: may affect absorptionfluphenazine. Antacids should be taken 1 hour before or 2-3 hours after fluphenazine injection.

Anorexigenic drugs are pharmacological antagonists of fluphenazine.

Isoenzyme substrates or inhibitorsCYP2 D6 :metabolized by isoenzymeCYP2 D6 and at the same time is an inhibitor of this isoenzyme. Consequently, the plasma concentration and effects of fluphenazine may increase with drugs that are also metabolized byCYP2 D6 or inhibit it, resulting in cardiotoxicity, adverse reactionscaused by m-anticholinergic action, or orthostatic hypotension.

Phenylpropanolamine : when interacting with fluphenazine, it can cause ventricular arrhythmia.

Imbalance of electrolytes in the blood (especially hypokalemia): greatly increases the risk of lengthening the intervalQT.

Monoamine oxidase (MAO) inhibitors, combined use enhances sedation, constipation, dry mouth, hypotension.

Methyldopa : increases the risk of developing extrapyramidal disorders.

Slow calcium channel blockers: their hypotensive effectincreases when combined with antipsychotics.

-Due to possible cross-sensitivity, the drug should be prescribed with caution to patients withallergic reactions a history of phenothiazine derivatives;

With development cholestatic jaundice as an adverse reaction, fluphenazine treatment should be discontinued;

-when conducting surgical operations patients taking high doses of phenothiazine derivatives may experience a sharp decrease in blood pressure;

-may require reduction doses anesthetics or antipsychotics in some patients during drug treatment; it is possible to potentiate the effect of m-anticholinergics, since it has an m-anticholinergic effect;

-should be used with caution ri very hot weather or poisoning with organophosphate insecticides , patients with convulsive seizures in the anamnesis;

-used with caution whenmitral valve insufficiency or others disorders of the cardiovascular system or with pheochromocytoma ;

-the drug should be prescribed with caution at breast cancer , since as a result of the prolactin secretion induced by phenothiazine derivatives, the risk of disease progression and resistance to treatment with endocrine and cytostatic drugs;

Development cases venous thromboembolism have been reported with antipsychotic medications. Because risk factors for venous thromboembolism are often present in patients taking antipsychotic drugs, it is necessary to assess these factors before and during treatment and take appropriate preventive measures;

-when prescribed to patients withparkinson's disease possibly increased extrapyramidal symptoms;

-arising in the form of side reactions extrapyramidal symptoms are generally reversible, but may be persistent. The likelihood and severity of such undesirable side reactions depends to a greater extent on individual sensitivity than on other factors, but the dose and age of the patient matter. The patient should be warned in advance about such manifestations and their reversibility. Usually, to eliminate these undesirable phenomena, it is sufficient to prescribe m-anticholinergics or antiparkinsonian drugs and / or reduce the dose of the drug;

In elderly patients, sedative and hypotensive effects may be expressed (see sections "Dosage and Administration" and "Side Effects").

Malignant neuroleptic syndrome

With the development of this adverse reaction, you should immediately stop taking antipsychotics and other drugs taken that do not affect the maintenance of vital functions, and you also need intensive symptomatic treatment, constant monitoring of vital functions and therapy for concomitant diseases.

Cerebrovascular accident and increased mortality in elderly patients with dementia

An approximately 3-fold increase in the risk of developing disorders of cerebral circulation was observed when taking some atypical antipsychotics in elderly patients withdementia history. There has been a slight increase in mortality in elderly patients with a history of dementia during antipsychotic drug therapy. The risk and causes of this phenomenon are unknown. It should be remembered that it is not indicated for the treatment of elderly patients with dementia.

Hypotension is rare during treatment with fluphenazine. At the same time, in patients with pheochromocytoma, cerebrovascular, renal and severe heart failure (for example, in patients with mitral valve insufficiency), hypotension develops more often while taking fluphenazine; these patients must be closely monitored.

With the development of severe hypotension, rapid intravenous administration of vasoconstrictor drugs is necessary. Best suited for this is injection. it is not recommended to use, since phenothiazine derivatives distort the reaction to, as a result of which there is an even greater decrease in blood pressure.

With the development of diseases of the mucous membranes of the mouth, gums or throat, or infections of the upper respiratory tract in combination with a change in the number of leukocytes, confirming the inhibition of hematopoiesis, fluphenazine therapy should be canceled, and the necessary therapeutic measures should be started immediately.

Sick with seizures a history of phenothiazine derivatives should be used with caution, including.

It should be borne in mind that the antiemetic effect of phenothiazine derivatives (including fluphenazine) can mask vomiting associated with an overdose of other drugs.

Abrupt withdrawal of the drug : Basically, taking phenothiazine derivatives does not cause mental dependence, however, there have been cases of nausea, vomiting, sweating, insomnia, dizziness with abrupt withdrawal of high doses of phenothiazine derivatives. These symptoms decreased with subsequent, after discontinuation of antiparkinsonian drugs for several weeks. The dose reduction should be gradual.

The preparation contains sesame oil, which in rare cases can cause severe allergic reactions.

The benzyl alcohol contained in the preparation can cause severe toxic and anaphylactoid reactions in children over 12 years of age.

Alcohol intake during drug treatment is prohibited.

Do not store the drug in the refrigerator, as this leads to precipitation of triglycerides that make up sesame oil. When a precipitate appears, the drug should be heated to 37 ° C, while the precipitate dissolves without losing the activity of the active substance.

The drug has a strong effect on the patient's psychomotor reactions, therefore, during the period of treatment, it is forbidden to work with mechanisms or drive a car.

Solution for intramuscular injection (oil), 25 mg / ml.

1 ml of the drug in vials, hermetically sealed with rubber stoppers and crimped with combined caps (aluminum with plastic safety caps).

5 bottles, together with instructions for use, are placed in a box made of cardboard box.

In a dark place at a temperature not exceeding 25 ° C.

Keep out of the reach of children.