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

Clinical and pharmacological group: & nbsp

Neuroleptics

Included in the formulation

Moditen® depot

solution w / m

KRKA, dd, Novo mesto, AO

Moditen® depot

solution w / m

Bristol-Myers Squibb France

Fluphenazine

solution w / m

R-PHARM, CJSC Russia

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

N.05.A.B.02 Fluphenazine

Pharmacodynamics:

Antipsychotic agent (neuroleptic), piperazine derivative of phenothiazine. Has a pronounced antipsychotic effect, combined with some activating effect.

It blocks central postsynaptic dopamine D2 -receptors in the mesolimbic and mesocortical system, which causes a pronounced antipsychotic effect.

Effectively eliminates the productive symptoms of psychosis, including delirium, hallucinations, impaired thinking,

Has a weak antiemetic effect, hypotensive effect, has some anticholinergic activity. Antiemetic action is due to blockade of dopamine D2 receptors in the chemoreceptor trigger zone of the cerebellum, as well as blockade of the vagus nerve in the digestive tract. The hypotensive effect is associated with blockade of α-adrenergic receptors.

Oppression of D2- and D5- Dopamine receptors in the tuberoinfundibular system cause hyperprolactinemia, hypothermia, increased appetite and obesity.

Oppression of D2- and D5- Dopamine receptors in the tuberoinfundibular system cause hyperprolactinemia (gynecomastia, galactorrhea), hypothermia, increased appetite and obesity.

Oppression of dopamine D2receptors in the basal ganglia (nigrostriral zone) leads to drug parkinsonism (extrapyramidal disorders).

Pharmacokinetics:

Clinical data on the pharmacokinetics of fluphenazine are limited.

Phenothiazines have a high binding to plasma proteins - 90 %. They are mainly excreted by the kidneys and partly by bile.

Half-life fluphenazine decanoate 163-232 h, fluphenazine hydrochloride 33 h, fluphenazine enanthate 84-96 h. Biotransformation in the liver (CYP 2D6, 1A2, 3A3, 3A4), inhibitor - CYP2D6. Elimination with feces. Not removed during hemodialysis

Indications:Psychotic disorders, including schizophrenia; states, accompanied by hyperactivity and excitement. Supportive treatment of chronic schizophrenia without the phenomena of agitation after reaching a stable state with the help of neuroleptics of shorter action (for depot form).

ICD-10

V.F20-F29.F20 Schizophrenia

V.F20-F29.F21 Chrysotile disorder

V.F20-F29.F22 Chronic delusional disorders

V.F20-F29.F25 Schizoaffective disorder

V.F20-F29.F28 Other Inorganic Psychotic Disorders

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F00-F09.F09 Organic or symptomatic mental disorder, unspecified

V.F40-F48.F48.9 Neurotic disorder, unspecified

V.F60-F69.F60.0 Paranoid personality disorder

XVIII.R40-R46.R45.0 Nervousness

XVIII.R40-R46.R45.1 Anxiety and Excitement

XVIII.R40-R46.R45.3 Demoralization and apathy

XVIII.R40-R46.R45.6 Physical aggressiveness

Contraindications:Hypersensitivitynost; heavy cardiovascular system(decompensated)chronic heart failure, arterial hypotension), severe CNS depression and coma of any etiology; brain trauma, progressive systemic diseases of the brain and spinal cord; pregnancy, breast-feeding, children's age (up to 12 years). Acute intoxication with substances depressing the central nervous system (alcohol, antidepressants, antipsychotics, sedatives, anxiolytics, hypnotics and opioid analgesics).

Carefully:

Alcoholism, pathological changes in the blood, breast cancer, angle-closure glaucoma, prostate hyperplasia,hepatic and / or renal failure, gastric and duodenal ulcer (exacerbation period), diseases accompanied by an increased risk of thromboembolic complications, Parkinson's disease, epilepsy, epileptic seizures in a history, myxedema, chronic diseases accompanied by respiratory failure (especially in children) , Reye's syndrome, cachexia, vomiting, elderly age.

Not recommended for use in children.

Pregnancy and lactation:

Recommendations for FDA - Category C. When pregnancy is possible, the use of the drug, if the expected effect of therapy exceeds the potential risk to the fetus In newborns, it is possible to develop withdrawal syndrome, acute rhinitis, vomiting, respiratory disorders, extrapyramidal symptoms. Administration of fluphenazine to animals at a dose of 5-6 mg / kg leads to a slowing of bone formation (ossification).

Penetrates into breast milk. Do not apply!

Dosing and Administration:

Individual. Inside adults and adolescents - 1-5 mg 2-3 times a day, children depending on age - 250-750 mcg 1-4 times a day.

When administered intramuscularly in the form of a dosage form of usual durationActions - 1,25-2,5 mg if necessary and taking into account tolerability every 6-8 hours; for the depleted or weakened patients and the elderly, the dose is 1-2.5 mg per day. In the form of a depot form is administered intramuscularly or subcutaneously - 12.5-25 mg every 1-4 weeks. It is possible to increase the single dose to 50 mg.

Intramuscularly or subcutaneously apply fluphenazine Decanoate in the form of depot form in children aged 5-12 years - at 3.125-12.5 mg every 1-3 weeks, 12 years and older - at 6.25-25 mg every 1-3 weeks.

Maximum doses: for adults with oral intake, the daily dose is 20 mg; for intramuscular administration a single dose with fluphenazine in the form of a dosage form of usual duration of action - 10 mg, depot form - 100 mg.

Side effects:

From the side CNS: akathisia, parkinsonian syndrome, tardive dyskinesia, mimic hyperkinesis, fatigue, dizziness, intellectual disabilities, convulsive reactions.

From the side digestive system: dry mouth, constipation, nausea, transient liver dysfunction.

From the side of cardio-vascular system: heart rhythm disturbances, decreased blood pressure, tachycardia.

From the side hematopoiesis system: leukopenia, thrombocytopenia.

From the side endocrine system: galactorrhea, gynecomastia in men, menstrual irregularities.

Dermatological reactions: photosensitization.

Allergic reactions: skin rash, itching.

Overdose:

Severe extrapyramidal disorders, marked drop in blood pressure, miosis, hypothermia, urinary retention, ECG changes, cardiac rhythm disturbances similar to those with quinidine overdose, sedation, impaired consciousness up to its loss with areflexia, convulsions and coma.

Treatment is symptomatic. With arrhythmias, sodium bicarbonate is effective and magnesium sulfate. Central M-holinoblokatory for correction of extrapyramidal disorders. In severe hypotension, it is recommended to appoint only norepinephrine; adrenaline can further reduce blood pressure.

Interaction:

Contraindicated the combination of 4-nitro-N - [(1RS) -1- (4-fluorophenyl) -2- (1-ethylpiperidin-4-yl) ethyl] benzamide hydrochloride with fluphenazine, potentially capable of causing a polymorphic ventricular tachycardia of the pirouette type.

Alprazolam. Strengthens (mutually) the depression of the central nervous system; Care should be taken when concomitant use is indicated.

Buprenorphine. Strengthens (mutually) the depression of the central nervous system.

Valproic acid. Against the background of valproic acid, CNS depression is increasing.

Haloperidol. Fluphenazine enhances (mutually) the effect.

Gatifloxacin. With the simultaneous use of gatifloxacin with fluphenazine interaction is possible (may affect the rhythm of cardiac activity).

Hydroxysin. Fluphenazine enhances (mutually) the effect; when co-administered, the dose is reduced by 50% - the risk of developing severe, even fatal, complications is high.

Glipizide. Fluphenazine weakens the effect. When combined, dose adjustment may be required.

Guangfing. Strengthens (in high doses) a sedative effect.

Diazepam. Strengthens (mutually) the depression of the central nervous system.

Diphenhydramine. Strengthens (mutually) the depression of the central nervous system (may increase the hypnotic effect).

Carbamazepine. Against the background of carbamazepine, biotransformation is accelerated.

Clonazepam. Potentiation of CNS depression.

Levodopa. With simultaneous application with fluphenazine, suppression of the action of levodopa is possible.

Lithium carbonate. The case of the development of neurotoxicity symptoms (tremor, rigidity of muscles, ataxia, weakness, vomiting, confusion) is described with simultaneous application of fluphenazine with lithium carbonate.

Maprotiline.With the simultaneous use of fluphenazine with maprotilinom may increase the risk of malignant neuroleptic syndrome.

Metoclopramide. Fluphenazine strengthens sedation, weakens the stimulation of motor activity of the gastrointestinal tract, increases (mutually) the likelihood of developing extrapyramidal disorders.

Metformin. Fluphenazine weakens the effect (may provoke hyperglycemia); combined use requires constant monitoring of the level of glycemia.

Nitroglycerine. Fluphenazine strengthens the hypotensive effect.

Pacireotid should be used with caution at the same time as fluphenazine, which can prolong the QT interval.

Promethazine. Fluphenazine strengthens and prolongs (mutually) sedative effect; when co-administered, the dose should be reduced.

Repaglinide. Fluphenazine weakens hypoglycemic effect; when combined appointment requires the control of glycemia.

Risperidone. Strengthens (mutually) the effect; Care must be taken when sharing.

Sotalol. Lengthens the QT interval; joint application is not recommended.

Topiramate. Strengthens (mutually) the depression of the central nervous system.

Tramadol. Fluphenazine increases the risk of seizures.

Cyproheptadine. With the combined use of cyproheptadine and fluphenazine, de-stimulation is mutually reinforced and the rate of psychomotor reactions decreases.

Epinephrine. With simultaneous application with fluphenazine, suppression of the action of adrenaline is possible.

Ethanol. With the simultaneous use of fluphenazine and ethanol, an increase in CNS and respiratory depression is possible.

Ephedrine. With the simultaneous use of fluphenazine with ephedrine, the vasoconstrictive effect of ephedrine may be reduced.

Special instructions:

With caution combine with hypertensive drugs in elderly patients and apply to workers in conditions of elevated temperature, having contact with phosphorus-containing insecticides. With prolonged therapy, it is necessary to control the number of leukocytes, conduct functional tests of the liver.

The development of tardive dyskinesia is more likely in elderly patients, especially in older women. The risk of developing this syndrome and the likelihood of its irreversibility increases with prolonged treatment and an increase in the total cumulative dose of neuroleptic. When signs or symptoms of tardive dyskinesia appear, consider discontinuingtreatment with fluphenazine (however, some patients may require continued treatment, despite the presence of the syndrome).

When symptoms of neuroleptic malignant syndrome appear, fluphenazine should be discontinued immediately and an intensive symptomatic treatment should be performed.

It should be remembered about the possibility of liver damage, the development of pigment retinopathy, deposits in the lens and cornea and irreversible dyskinesia during long-term therapy.

During treatment, one should not engage in activities requiring increased attention, rapid mental and motor reactions.

Instructions

Fluphenazine (Fluphenazinum)