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

Active substanceFluphenazineFluphenazine

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R-PHARM, CJSC Russia

Dosage form: & nbspSolution for intramuscular administration [oily].

Composition:

1 ml of the solution contains:

active substance: fluphenazine decanoate - 25 mg;

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

Description:

Transparent, oily liquid of yellowish color. May have a faint smell of benzyl alcohol.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.B.02 Fluphenazine

Pharmacodynamics:

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 neuroleptics - it has a pronounced antipsychotic effect, combined with some activating effect, as well as a moderate sedative effect, has antiemetic effect.

The antipsychotic effect is due to the blockade of dopamine D₂receptors of the mesolimbic and mesocortical system. Sedative action (moderately expressed and observedwhen used in high doses) is due to blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D₂receptors of the trigger zone; hypothermic action - blockade of dopamine receptors of the hypothalamus.

The effect of the drug usually manifests itself 24-72 hours after the injection, the antipsychotic effect is most pronounced in terms of 48 to 96 hours after intramuscular injection.

Pharmacokinetics:

Suction

Fluphenazine decanoate is slowly absorbed in the injection area and hydrolyzed in plasma to the active substance - fluphenazine.

Distribution

Fluphenazine in the form of a high-molecular fatty acid ester and an oily solution is accumulated in fat stores and slowly released.

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

Fluphenazine passes through 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, isoenzyme CYP2D6) and is excreted in the urine and bile.The activity of fluphenazine metabolites has not been studied.

Excretion

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

Indications:

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

Prevention of exacerbations of schizophrenia.

Contraindications:

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

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

- pronounced atherosclerosis of cerebral vessels;

- severe cardiovascular diseases (decompensated chronic circulatory failure, arterial hypotension);

- pronounced central nervous system (CNS) function depression and comatose states of any etiology; craniocerebral trauma, progressive systemic diseases of the brain and spinal cord;

- hepatic and / or renal insufficiency;

- blood diseases;

- severe depression;

- pheochromocytoma;

- pregnancy, lactation;

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

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

Carefully:

- Alcohol dependence (increased predisposition to hepatotoxic reactions);

- abnormal liver function;

- impaired renal function;

- allergic reactions to phenothiazine derivatives in the anamnesis;

- application in very hot weather;

- breast tumors;

- angle-closure glaucoma;

- Myasthenia gravis (Myasthenia gravis);

- hyperplasia of the prostate with clinical manifestations;

- Stomach ulcer and duodenal ulcer (during exacerbation);

- diseases accompanied by an increased risk of thromboembolic complications;

- Parkinson's disease;

- epilepsy, convulsive fits in the anamnesis;

- heart rhythm disturbances;

- hypothyroidism (myxedema) and hyperthyroidism (thyrotoxicosis);

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

- Reye syndrome (increased risk of increased hepatotoxicity in adolescents);

- cachexia;

- vomiting;

- elderly age, especially in weakened and / or at risk of developing hypothermia in patients;

- patients who have a history of cardiovascular disease, before the appointment of fluphenazine, it is necessary to make an ECG and carry out correction of the electrolyte balance.

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

Pregnancy and lactation:

Pregnancy Period: the safety of fluphenazine when used in pregnant women is not established, so the drug should be prescribed only if the expected benefit for the mother exceeds the potential risk to the fetus.

Newborns, whose mothers took antipsychotics in the third trimester, are at increased risk of developing extrapyramidal disorders and withdrawal symptoms. The duration and severity of the symptoms may vary. There was anxiety, hypertension, hypotension, tremor, drowsiness, respiratory and / or feeding disorders.

Breastfeeding period: fluphenazine can be excreted into breast milk, so taking fluphenazine during lactation is not recommended.

Dosing and Administration:

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

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

Adults

Recommended doses for all indications

Patients who had not previously taken the drug in the form of decanoate (fluphenazine sustained release)

Initial dose - deeply intramuscularly to 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 administrations are determined individually depending on the response to treatment.

The manifestation of the pharmacological effect is usually noted between 24 and 72 hours after the injection, and a marked decrease in psychotic symptoms occurs after 48-96 hours. It is necessary to observe the maximum flexibility in determining the dosage to provide the optimal therapeutic response with minimal side effects; most patients manage to achieve optimal maintenance therapy at dosages of 0.5 ml (12.5 mg) to 4.0 ml (100 mg) with the administration of the drug every 2-5 weeks.

Supportive therapy

When using fluphenazine as maintenance therapy, one injection provides control over the manifestations of schizophrenia for 4-6 weeks. It is necessary to select an individual dose with minimal side effects. In most patients, the necessary pharmacological effect is achieved by the administration of fluphenazine at doses of 0.5 ml (12.5 mg) to 4.0 ml (100 mg) at intervals 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. With the cessation of therapy, relapse can only occur after a few weeks or months.

Patients with severe agitation

Fluphenazine decanoate is prescribed after arresting excitation with other antipsychotics, including injectable ones. After relief of acute manifestations, 25 mg (1 ml) of flufenazine decanoate solution can be administered; the subsequent doses are adjusted if necessary.

Patients who had previously taken oral antipsychotics

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

Patients previously taking fluphenazine in the form of decanoate (long-acting injection)

If there is a relapse of schizophrenia after the discontinuation of fluphenazine therapy with decanoate, 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 young patients. Elderly patients may show increased sensitivity to the drug in the form of increased frequency of extrapyramidal reactions, sedative and hypotensive effects (see the sections "Side effects" and "Special instructions").

Patients under the age of 12 years

It is not recommended to apply (see the section "Contraindications").

Method of administration: intramuscularly.

Side effects:

Violations of the blood and lymphatic system

Leukopenia, agranulocytosis, thrombocytopenic and netrombotsitopenicheskaya purpura, eosinophilia and pancytopenia.

Immune system disorders

Hypersensitivity reactions, anaphylactic reactions.

Disorders from the metabolism and nutrition

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

Disorders of the psyche

Agitation, emotional arousal, insomnia.

Disturbances from the nervous system

- acute extrapyramidal disorders, such as extrapyramidal syndrome, dystonia, dyskinesia, akathisia, oculogy crisises, opisthotonus and hyperreflexia, tardive dyskinesia (a syndrome manifested by involuntary choreoathetoid movements of the tongue, facial muscles, mouth, lips or jaw (for example, protruding the tongue, inflating the cheeks, stretching of the lips, chewing movements) of the muscles of the trunk and extremities) usually develop during the first 24-48 hours;

- malignant neuroleptic syndrome (CNS) with possible fatal outcome (hyperpyrexia, rigidity of muscles, changes in mental state,vegetative disorders - fluctuations in heart rate or blood pressure, tachycardia, increased sweating, heart rhythm disturbances), ZNS can also be accompanied by the development of leukocytosis, fever, increased activity of creatine phosphokinase (CK), impaired liver function and acute cardiac renal insufficiency, akinesia; drowsiness, confusion (sometimes turning into a stupor or to whom), changes in the encephalogram and protein content in cerebrospinal fluid, cerebral edema;

- Parkinson-like conditions can develop between the second and fifth days after injection, but often decrease after subsequent injections;

- tardive dyskinesia, the severity of this syndrome and the resulting worsening of the condition can vary significantly in different patients. Late dyskinesia is manifested either during treatment with a reduced dose, or after discontinuation of therapy.

Early detection of tardive dyskinesia is very important. To detect this syndrome at the initial stage, it is recommended that the dose of the antipsychotic is periodically reduced (if possible by the patient's condition) and that the patient is monitored during this period.This approach is extremely important, since treatment with neuroleptics may mask the manifestations of tardive dyskinesia. Headache, epileptiform attacks, convulsive attacks.

In elderly patients, sedative and hypotensive effects can be expressed (see the section "Dosing and Administration" and "Special instructions").

Disturbances on the part of the organ of sight

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

Heart Disease

Interval lengthening QT, ventricular arrhythmias, including ventricular fibrillation, ventricular tachycardia, cardiac arrest, sudden death.

Vascular disorders

Hypotension, including orthostatic hypotension, fluctuations in blood pressure.

The frequency is unknown: deep vein thrombosis, venous thromboembolism.

Disturbances from the respiratory system and mediastinal organs

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

The frequency is unknown: laryngeal edema (with prolonged use of the drug).

Disorders from the gastrointestinal tract

Nausea, constipation, dry mouth, intestinal obstruction.

Disturbances from the liver and bile ducts

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

Disturbances from the skin and subcutaneous tissues

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

Disturbances from musculoskeletal and connective tissue

Very rarely: systemic lupus erythematosus.

Disorders from the kidneys and urinary tract

Difficulty urinating, urinary incontinence, atony of the bladder, kidney failure.

Pregnancy, postpartum and perinatal conditions

Frequency unknown: withdrawal syndrome in newborns.

Violations of the genitals and mammary gland

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

Laboratory and instrumental data:

Changes in liver function indicators, reported rare transient increases in serum cholesterol in patients receiving fluphenazine orally.

Very rare: appearance antinuclear antibodies.

If any of the side effects listed in the manual are aggravated or you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

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

With the development of severe hypotension, immediate intravenous administration of vasoconstrictive drugs is necessary.

Epinephrine (adrenaline) it is not recommended to apply, since simultaneous administration with phenothiazine derivatives there is an even greater decrease in blood pressure.

When development of severe extrapyramidal disorders is prescribed antiparkinsonics for several weeks. Antiparkinsonics should be phased out gradually in order to avoid recurrence of extrapyramidal disorders.

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

Interaction:

Fluphenazine enhances the effects of deprivation aalcohol, sleeping pills and sedatives; increases the effect anticoagulants, cardiodepressive action quinidine, suction corticosteroids, digoxin, muscle relaxants.

Simultaneous application with narcotic analgesics can cause hypotension, depression of the central nervous system and respiration.

Tricyclic antidepressants: phenothiazine derivatives disrupt metabolism of tricyclic antidepressants. Serum concentrations of both tricyclic antidepressants and phenothiazines increase. Sedation and m-cholinoblocking effects may be prolonged or prolonged, as well as the arrhythmogenic effect of tricyclic antidepressants.

Lithium preparations with simultaneous application with fluphenazine may increase neurotoxicity.

Angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics: possibly increased hypotensive effect (pronounced postural hypotension).

Other antihypertensives: the antihypertensive effect of guanethidine, clonidine and possibly other anti-adrenergic agents may be reduced. Clonidine can reduce the antipsychotic effect of phenothiazines.

Beta-blockers: can increase concentrations of beta-adrenoblockers and derivatives of phenathiazine in blood plasma.

With the simultaneous use of beta-adrenoblockers and phenothiazine derivatives, a reduction in the dose of drugs of both groups is recommended.

Metrizamide can cause convulsive seizures amid the use of fluphenazine. Recommended to cancel fluphenazine 48 hours before myelography and do not prescribe it at least 24 hours after myelography.

Eninephrine and other adrenomimetics: derivatives of phenothiazine are their pharmacological antagonists, as a result of which development of severe hypotension is possible.

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

M-holinoblokatory: when fluphenazine is administered in combination with m-holinoblokatorami possible strengthening of the blocking of cholinergic receptors, especially in the elderly. M-cholinoblocking effects are potentiated or prolonged.

When using the drug Fluphenazine At the same time as m-holinoblokatorami careful monitoring and selection of doses of drugs is necessary.

Anticonvulsants: flufenazine can reduce them anticonvulsant effect.

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

Fluphenazine may contribute to lengthening the interval QT, which may increase the risk of ventricular arrhythmias such as pirouettes, which are potentially dangerous (risk of "sudden death"). Interval lengthening QT especially increased in the presence of bradycardia, hypokalemia and congenital or acquired lengthening interval QT.

Joint use of drugs that extend the interval QT and fluphenazine is contraindicated. Examples are certain antiarrhythmic drugs, for example, class IA (including, quinidine, disopyramide and procainamide) and III class (including, amiodarone and sotalol), tricyclic antidepressants (including, amitriptyline), certain tetracyclic antidepressants (such as maprotiline), certain antipsychotics (including phenothiazides and pimozide), certain antihistamines (including terfenadine, lithium, quinine, pentamidine, and sparfloxacin).

Inhibitors of serotonin reuptake: inhibit the metabolism of phenothiazines.

Hypoglycemic agents: derivatives of phenothiazine cause decompensation of diabetes mellitus.

Cimetidine: can reduce the concentration of phenothiazine derivatives in plasma blood.

Antacids / antidiarrhoeals: may affect absorption flufenazine. Take antacids should be 1 hour before or 2-3 hours after the injection of fluphenazine.

Anorexigenic agents are pharmacological antagonists of fluphenazine.

Substrates or inhibitors of the isoenzyme CYP2D6: fluphenazine is metabolized by isoenzyme CYP2D6 and at the same time is an inhibitor of this isoenzyme. Consequently, plasma concentrations and effects of fluphenazine may increase with the administration of drugs that are also metabolized by CYP2D6 or inhibit it, resulting in cardiotoxicity, adverse reactions caused by m-holin-blocking action, or orthostatic hypotension.

Phenylpropanolamine: when interacting with fluphenazine may cause ventricular arrhythmia.

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

Inhibitors of monoamine oxidase (MAO), joint use increases sedation, constipation, dryness of the oral mucosa, hypotension.

Methyldopa: increases the risk of developing extrapyramidal disorders.

Blockers of slow calcium channels: their hypotensive effect intensified when combined with antipsychotics.

Special instructions:

- In connection with the possible cross-sensitivity, caution should be given to administering the drug to patients with allergic reactions on phenothiazine derivatives in the anamnesis;

- when developing cholestatic jaundice as an adverse reaction, treatment with fluphenazine should be discontinued;

- in carrying out surgical operations patients who take high doses of phenothiazine derivatives, there may be a sharp drop in blood pressure;

- may require a reduction doses anesthetics or antipsychotics in some patients with drug treatment; Potentiation of the effect of m-holinoblokatorov is possible, since fluphenazine has m-anticholinergic action;

- should be cautiously appointed fluphenazine Pri very hot weather or poisoning with organophosphorous insecticides, patients with convulsive seizures in the anamnesis;

- use with caution when Mitral valve insufficiency or other disorders of the cardiovascular system or with pheochromocytoma;

- should be used with caution at breast cancer, because as a result of the phenothiazine-induced secretion of prolactin, the risk of disease progression and resistance to endocrine and cytotoxic drugs increases;

- cases of development venous thromboembolism were noted when taking antipsychotic medications. Since patients who take antipsychotic medications often have risk factors for venous thromboembolism, it is necessary to assess these factors before and during treatment and take appropriate preventive measures;

- when administered to patients with Parkinson's disease possibly increased extrapyramidal symptoms;

- arising as side reactions extrapyramidal symptoms, as a rule, they are reversible, but they can also be resistant. The likelihood of occurrence and severity of such undesirable side reactions depends more on the individualsensitivity than from other factors, but the magnitude of the dose and age of the patient are important. The patient should be warned in advance about such manifestations and their reversibility. Usually, m-cholinoblockers or antiparkinsonian drugs and / or dose reduction are sufficient to eliminate these undesirable phenomena;

- in elderly patients, sedative and hypotensive effects can be expressed (see the sections "Dosing and Administration" and "Side effects").

Malignant neuroleptic syndrome

With the development of this adverse reaction should immediately stop taking neuroleptics and other medications that do not affect the maintenance of vital functions, as well as intensive symptomatic treatment, continuous monitoring of vital functions and therapy of concomitant diseases.

Violation of cerebral circulation and increased mortality of elderly patients with dementia

Approximately 3-fold increase in the risk of developing cerebrovascular disorders was observed with some atypical antipsychotics in elderly patients with dementia in the anamnesis.There was a slight increase in the mortality of elderly patients with a history of dementia during antipsychotic medication therapy. The degree of risk and the causes of this phenomenon are unknown. It should be remembered that fluphenazine is not indicated for the treatment of elderly patients with dementia.

Hypotension against treatment with fluphenazine is rare. At the same time in patients with pheochromocytoma, cerebrovascular, renal and severe heart failure (for example, in patients with mitral valve insufficiency), hypotension with fluphenazine is more frequent; careful monitoring is necessary for these patients.

With the development of severe hypotension, rapid intravenous administration of vasoconstrictive drugs is necessary. Best for this is suitable norepinephrine for injections. Epinephrine It is not recommended to use it, because phenothiazine derivatives distort the reaction to epinephrine, resulting in an even greater reduction in blood pressure.

With the development of diseases of the mucous membrane of the mouth, gums or throat, or infection of the upper respiratory tract in combination with a change in the number of leukocytes,confirming oppression of hematopoiesis, therapy with fluphenazine should be canceled, and the necessary medical measures are immediately started.

Patients with convulsive seizures in the history it is necessary to appoint with caution the derivatives of phenothiazine, including fluphenazine.

It should be taken into account that the antiemetic effect of phenothiazine derivatives (including fluphenazine) may mask vomiting associated with overdose of other medications.

Drastic withdrawal of the drug: in general, the reception of phenothiazine derivatives does not cause psychic dependence, however, cases of nausea, vomiting, sweating, insomnia, dizziness were observed with a sharp abolition of high doses of phenothiazine derivatives. These symptoms decreased with subsequent withdrawal after taking antiparkinsonian drugs for several weeks. Dose reduction should be gradual.

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

Benzyl alcohol contained in the preparation can cause severe toxic and anaphylactoid reactions in children older than 12 years.

The intake of alcohol during treatment with the drug is prohibited.

Do not store the drug in the refrigerator, as this leads to the precipitation of triglycerides, which are part of sesame oil. When a precipitate appears, the preparation should be heated to 37 ° C, while the precipitate dissolves without loss of activity of the active substance.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Solution for intramuscular administration (oily), 25 mg / ml.

Packaging:

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

For 5 bottles together with the instructions for use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003634

Date of registration:16.05.2016

Expiration Date:16.05.2021

The owner of the registration certificate:R-PHARM, CJSC R-PHARM, CJSC Russia

Manufacturer: & nbsp

R-PHARM, JSC Russia

Representation: & nbspR-PHARM, JSC R-PHARM, JSC Russia

Information update date: & nbsp12.07.2016

Illustrated instructions

Instructions

Fluphenazine (Fluphenazine)