Active substancePerphenazinePerphenazine
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  • Etperazine
    pills inwards 
  • Dosage form: & nbspcoated tablets
    Composition:

    1 tablet coated film contains:

    Active substance:

    Perphenazine dihydrochloride
    (Etaperazine) .............................
    - 4.0 mg.................. - 6.0 mg................- 10.0 mg

    Excipients:

    lactose monohydrate .................- 86.0 mg.................- 111.0 mg..............- 125.0 mg

    potato starch.............- 9.0 mg..................- 11.70 mg..............- 13.50 mg

    calcium stearate ........................- 1.0 mg - 1.30 mg.................- 1.50 mg

    Shell accessories:

    sucrose....................................- 61.702 mg..............- 67.872 mg.............- 92.553 mg

    magnesium hydroxycarbonate ......- 34.169 mg..............- 37.586 mg..............- 51.254 mg

    Povidone ...................................- 0.669 mg .................. - 0.736 mg ................ - 1.004 mg

    silicon dioxide
    colloidal............................
    - 2.228 mg .................-2.451 mg .................- 3.342 mg

    tropeolin O...........................- 0.011 mg ................. - .......................... -



    quinoline yellow ...........-..................................- .............................- 0.131 mg


    indigo carmine .......................-..................................- .............................- 0.011 mg

    titanium dioxide.......................- 1.073 mg ..................- 1,192 mg ...............- 1.485 mg

    beeswax.......................- 0.148 mg ..................0.163 mg.- 0.220 mg

    Description:

    The tablets are coated, round, biconvex, with a dosage of 4 mg - from light yellow to yellow, 6 mg - white, 10 mg - from yellowish-green to green. On the fracture of the tablets, two layers are visible: a 4 mg dosage is a white or white core with a grayish hue and a coat of light yellow to yellow, 6 mg - the core of white or white with a grayish hue of color and a shell of white color, 10 mg - the core of white or white with a grayish shade of color and a coat from yellowish green to green.

    Pharmacotherapeutic group:Antipsychotic agent (antipsychotic).
    ATX: & nbsp

    N.05.A.B.03   Perphenazine

    Pharmacodynamics:

    Antipsychotic agent (neuroleptic), a phenothiazine derivative; has a sedative. antiallergic, weak anticholinergic, antiemetic, myorelaxing. weak hypotensive and hypothermic action, eliminates hiccups. The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical system. The blockade of D2-dopamine receptors in the polyneuronal synapses of the brain causes a reduction in the productive symptoms of psychosis: delusions and hallucinations. Antipsychotic action is combined with a pronounced activating influence and selective effect on the syndromes that occur with retardation, lethargy, apathy, primarily with sub-stuporic phenomena, as well as apathoabulic conditions. Sedative action is due to blockade of adrenoreceptors of the reticular formation of the brain stem. Severity of sedation - from mild to moderate. Has a strong antiemetic effect. Antiemetic activity is associated with inhibition of the trigger zone of the vomiting center due to blockadeD2-dopamine receptors (central action) and a decrease in secretion and motility of the gastrointestinal tract (GIT) as a result of blockade of m-cholinergic receptors (peripheral action). Inhibition of dopamine receptors in the nigrostriral zone and tubuloinfundibular region may result in extrapyramidal disorders and hyperprolactinaemia. Peripheral alpha-adrenoblocking effect is manifested by a decrease in arterial pressure (hypotensive effect is weakly expressed), and H1antihistamine - antiallergic action. Hypothermic action - blockade of dopamine receptors of the hypothalamus. Antipsychotic activity exceeds chlorpromazine. The antipsychotic effect develops after 4-7 days and reaches a maximum after 1.5-6 months (depending on the nature of the disease).

    Pharmacokinetics:

    Like all phenothiazine derivatives, it is well absorbed in the gastrointestinal tract. Binding to plasma proteins - 90%. Bioavailability is 40% after ingestion. Perphenazine is extensively metabolized in the liver by sulfoxylation, hydroxylation, dealkylation, and glucuronation to form a number of metabolites.Among patients taking phenothiazine derivatives, there are significant fluctuations in the maximum plasma concentration. Hydroxylation of perfenazine is carried out with the participation of an isoenzyme CYP 2D6 enzymatic system of cytochrome P450 and, therefore, depends on genetic polymorphism, that is, from 7% to 10% of the population of the Caucasus and a small percentage of the population of Asia have a low or completely absent activity, the so-called "low" metabolism. In patients with a "low" metabolism CYP 2D6 perphenazine will be absorbed more slowly, and they will have higher concentrations of etaperazine in the blood plasma compared to patients who have normal or "high" metabolism.

    After ingestion of perphenazine, its maximum concentration in the plasma, according to studies, is observed after 1-3 hours, 7-hydroxyperphenazine - 2-4 hours. The average equilibrium maximum concentrations (Cmax) are 984 pg / ml and 509 pg / ml, respectively. Time to reach the equilibrium concentration (Css) when ingested - 72 hours.

    It is excreted mostly by the kidneys and partly by the bile. The half-life of perphenazine is independent of the dose and is 9-12 hours, 7-hydroxyperphenazine 10-19 hours.

    Indications:

    - Schizophrenia in adults.

    - Severe nausea and vomiting in adults.

    Contraindications:

    - severe toxic oppression of the central nervous system (CNS) and comatose states of any etiology;

    - patients taking high doses of drugs depressing the central nervous system (barbiturates, alcohol, anesthesia, analgesics, antihistamines);

    - oppression of bone marrow hematopoiesis;

    - disorders of hematopoiesis;

    - severe renal or hepatic impairment;

    - decompensated hypothyroidism;

    - subcortical brain damage with or without hypothalamus function disorder;

    - progressive systemic diseases of the brain and spinal cord;

    - late stages of bronchiectasis;

    - diseases accompanied by a risk of thromboembolic complications;

    - hypersensitivity to the components of the drug;

    - cardiovascular diseases in the stage of decompensation;

    - violation of intracardiac conduction;

    - deficiency of lactase, sucrose / isomaltase;

    - intolerance to lactose, sucrose;

    - glucose-galactose malabsorption.

    Carefully:

    Alcoholism (predisposition to hepatotoxic reactions); pathological changes in blood; breast cancerglands (as a result of prolactin-induced phenothiazine secretion, the potential risk of disease progression and resistance to drugs assigned to patients with endocrine and metabolic diseases and cytostatic drugs increases); angle-closure glaucoma; hyperplasia of the prostate with clinical manifestations; renal or hepatic insufficiency of mild and moderate degree; peptic ulcer of stomach and duodenum (during exacerbation); diseases accompanied by an increased risk of thromboembolic complications; Parkinson's disease (extrapyramidal effects are intensified); epilepsy; chronic diseases accompanied by respiratory failure (especially in children); Reye syndrome (increased risk of hepatotoxicity in children and adolescents); cachexia; vomiting (antiemetic effect of phenothiazine derivatives may mask vomiting associated with overdose with other drugs); patients in the period of alcohol withdrawal; depression (the possibility of suicide persists); elderly age.

    Pregnancy and lactation:

    Perphenazine easily penetrates the placental barrier and is quickly excreted in breast milk, so the possibility of using the drug is determined by the doctor if the potential benefit to the mother exceeds the potential risk to the fetus or the baby.

    In newborns whose mothers took perphenazine at the end of pregnancy or during childbirth, there may be signs of intoxication, such as lethargy, tremors and excessive excitability. In addition, such neonates have a low Apgar score.

    With prolonged treatment of the mother, or with the use of high doses, as well as in the case of the appointment of the drug shortly before the birth, the monitoring of the activity of the nervous system of the newborn is justified.

    Dosing and Administration:

    Inside, after eating. Older patients are acceptable before bedtime.

    Doses are selected individually according to the severity of the condition.

    Older patients, who are depleted and weakened, usually require a smaller initial dose.

    When the maximum therapeutic effect is achieved, the dose is gradually reduced to a supporting dose.

    Schizophrenia: adults previously untreated antipsychotic drugs, the initial dose is 4-8 mg 3 times a day. Patients with a chronic course of the disease, if necessary, increase the dose to 64 mg / day. The duration of treatment depends on the patient's condition and the severity of side effects and is 1-4 months or more.

    Severe nausea and vomiting :, adults as an anti-emetic drug are prescribed for 8-16 mg 2-4 times a day.

    Side effects:

    Not all of the following side effects were recorded with perphenazine. However, pharmacological similarity with other phenothiazine derivatives requires that each be considered. Many of these side effects can be avoided by lowering the dose.

    From the nervous system and sensory organs: extrapyramidal disorder (especially dystonic) - spasm of the muscles of the back and neck, face, tongue, tonic spasm of the masticatory muscles, difficulty in speaking and swallowing, the feeling of stiffness in the throat, oculogyric crises, spasms and pain in the limbs, stiffness of arms and legs, hyperreflexia, akathisia . parkinsonism, ataxia; drowsiness, inhibition, lethargy,muscle weakness, decreased motivation, dizziness, miosis, mydriasis, blurred vision, glaucoma, pigmentary retinopathy, crystalline and corneal deposits, paradoxical reactions - exacerbation of psychotic symptoms, catalepsy, catatonic-like conditions, paranoid reactions, lethargy, inhibition, paradoxical agitation, anxiety, hyperactivity, night confusion, strange dreams, sleep disturbance. Their frequency and severity usually increase with increasing dose, but there are significant individual differences in the propensity to develop such symptoms. Extrapyramidal symptoms, as a rule, are corrected by simultaneous application of effective antiparkinsonian drugs or dose reduction. In some cases, however, these extrapyramidal reactions may persist after the abolition of perphenazine treatment.

    Late dyskinesia: rhythmical, involuntary movements of the tongue, face, mouth and jaw (for example, bulging tongue, inflating the cheeks, wrinkling of the mouth, chewing movements). Sometimes this can be accompanied by involuntary limb movements.There is no effective remedy for the treatment of tardive dyskinesia. There is evidence that vermicular movements of the tongue may be an early sign of the syndrome and if treatment is stopped - this syndrome may not develop.

    From the cardiovascular system: increase and decrease in blood pressure. orthostatic hypotension, change in pulse rate, tachycardia (especially with sudden significant increase in dose), bradycardia, cardiac arrest, weakness and dizziness, arrhythmia, fainting, changes in electrocardiogram, nonspecific (quinidine-like effect).

    From the blood (blood, gemostaz): leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, thrombopenic purpura, pancytopenia.

    On the part of the digestive system: nausea, vomiting, diarrhea, constipation, anorexia, increased appetite and body weight, polyphagia, abdominal pain, dry mouth, increased salivation, liver damage (bile stasis), cholestatic hepatitis, jaundice.

    Allergic reactions: skin rash, urticaria, erythema, eczema, exfoliative dermatitis, itching. hyperhidrosis, photosensitivity of the skin, bronchial asthma, fever, anaphylactoid reactions, laryngeal edema and Quinck edema, angioedema.

    Other: pallor, sweating, atony of the intestine and bladder, urinary retention. urination or urinary incontinence, polyuria, nasal canal blockage, kidney damage, increased intraocular pressure, skin pigmentation, photophobia, unusual breast milk secretion, breast enlargement and galactorrhea in women, gynecomastia in men, menstrual disorder, amenorrhea, changes in libido, decrease in ejaculation, syndrome of inadequate secretion of antidiuretic hormone, false positive pregnancy test, hyperglycemia, hypoglycemia, glucosuria. peripheral edema, systemic lupus erythematosus, as a syndrome.

    Malignant neuroleptic syndrome: hyperthermia, muscle rigidity, changes in mental status, autonomic instability (irregular pulse and fluctuations in blood pressure, tachycardia, sweating, and cardiac arrhythmia).
    Overdose:

    When an overdose of the drug, the appearance of acute neuroleptic reactions. Particularly should alarm the increase in body temperature, which may be one of the symptoms of malignant neuroleptic syndrome.In severe cases of overdose, various forms of impairment of consciousness, up to coma, can occur. Excess therapeutic dosages of perphenazine may be accompanied by extrapyramidal reactions, changes in the electrocardiogram - lengthening of the interval QTc, expansion of the complex QRS.

    Measures of help: discontinuation of therapy with neuroleptics, appointment of correctors, intravenous diazepam, glucose solution, symptomatic therapy.
    Interaction:

    With the simultaneous use of etazerazina with other drugs it is possible:

    - with drugs that have a depressing effect on the central nervous system (drugs for anesthesia, narcotic analgesics, ethanol and containing drugs, barbiturates, tranquilizers, etc.) increased oppression of the central nervous system, as well as respiratory depression;

    - with tricyclic antidepressants, maprotiline, or monoamine oxidase inhibitors - the lengthening and strengthening of sedative and m-cholinoblocking effects is possible, an increased risk of developing a malignant neuroleptic syndrome.

    - with anticonvulsants - it is possible to lower the threshold of convulsive readiness;

    - with drugs for the treatment of hyperthyroidism - increases the risk of agranulocytosis;

    - with other drugs that cause extrapyramidal reactions - it is possible to increase the frequency and severity of extrapyramidal disorders;

    - with antihypertensive drugs - possible pronounced orthostatic hypotension;

    - with ephedrine - it is possible to weaken the vasoconstrictive effect of ephedrine. Simultaneous use with tricyclic antidepressants, selective serotonin reuptake inhibitors, for example, fluoxetine, sertraline and paroxetine. which inhibit the cytochrome P isoenzyme450 2D6 (CYP 2D6), can dramatically increase plasma concentrations of phenothiazine derivatives and other antipsychotic drugs. When prescribing these drugs to patients already receiving antipsychotic therapy, careful observation is important and a dose reduction may become necessary to avoid side effects and toxicity. The appointment of alpha and beta-adrenomimetics (epinephrine) and sympathomimetics (ephedrine) can lead to a paradoxical decrease in blood pressure.The antiparkinsonian effect of levodopa is reduced due to the blocking of dopamine receptors. Perphenazine can suppress the effects of amphetamines, clonidine, guanetidine.

    Perphenazine increases the m-cholinoblocking effects of other drugs, while the antipsychotic effect of the antipsychotic may decrease.

    With simultaneous application perphenazine with a prochlorperazine related to the chemical structure, there may be a prolonged loss of consciousness.

    When combined with anti-Parkinsonian drugs, with lithium preparations, there is a decrease in absorption in the gastrointestinal tract. With simultaneous use with lithium preparations, the rate of elimination of lithium salts by the kidneys increases, and the severity of extrapyramidal disorders increases. Early signs of intoxication with lithium salts (nausea and vomiting) may be masked by the antiemetic effect of perphenazine.

    Aluminum- and magnesium-containing antacid drugs or antidiarrheal adsorbents reduce the absorption of perphenazine.

    Perphenazine can increase blood sugar and disrupt the control of diabetes. It is necessary to adjust the dose of antidiabetic drugs.

    Reduces the effect of anorectic drugs (with the exception of fenfluramine).

    Reduces the effectiveness of the emetic action of apomorphine, strengthens its inhibitory effect on the central nervous system.

    Increases the concentration in the plasma of prolactin and prevents the action of bromocriptine. Probucol, astemizole. cisapride, disopyramide, erythromycin, pimozide, procainamide and quinidine promote additional lengthening of the interval Q-T, which increases the risk of developing ventricular tachycardia.

    When combined with thiazide diuretics - increased hyponatremia. The combination with beta-adrenoblockers promotes the intensification of the hypotensive effect, increases the risk of developing irreversible retinopathy, arrhythmias and tardive dyskinesia. Drugs that inhibit bone marrow hematopoies increase the risk of myelosuppression.

    Special instructions:

    Elderly patients with psychoses due to dementia who received antipsychotics have an increased risk of death.

    Extrapyramidal disorders often occur when taking high doses. Late dyskinesia often develops in elderly patients, especially in women, whereas dystonia is more common in younger people.When signs or symptoms of tardive dyskinesia appear, consideration should be given to stopping treatment with an antipsychotic (however, some patients may require continued treatment, despite the presence of the syndrome).

    Perphenazine can reduce the convulsive threshold, so caution should be exercised when using the drug in patients with a predisposition to convulsive disorders and with alcohol withdrawal. With the simultaneous treatment of perphenazine and anticonvulsant drugs, an increase in the dose of the latter may be required.

    When using perphenazine, alcohol should be avoided. may have an additive effect and hypotension. The risk of suicide and the risk of an overdose of antipsychotics may be increased in patients who abuse alcohol during treatment, due to the potentiation of the depressive effect of the drug on the central nervous system.

    Care should be taken when prescribing the drug to patients with depression. The possibility of suicide in such patients during treatment is preserved, so it is necessary to exclude them access to a large number of medicines during treatment until the onset of complete remission.

    It should be used with caution perphenazine in patients with previously observed serious side effects when taking other phenothiazines. Some of the adverse reactions of perphenazine often appear when taking high doses. Perphenazine Use with extreme caution to persons exposed to heat or cold, because phenothiazine derivatives inhibit the mechanism of temperature regulation and, depending on the ambient temperature, can lead to hyperthermia and heat stroke or hypothermia and respiratory failure. A significant rise in body temperature can be caused by individual hypersensitivity. In the case of hyperthermia, treatment should be immediately withdrawn. Perphenazine increases the sensitivity of the body to the action of sunlight. It is recommended to use sunscreen, especially if patients have light skin and wear protective clothing while staying outdoors, and avoid prolonged sun exposure, visits to tanning beds and the use of ultraviolet lamps.

    It should be used with caution perphenazine in patients,suffering from respiratory system disorders due to the possible development of acute pulmonary infection, as well as in chronic respiratory diseases such as bronchial asthma or emphysema.

    Antipsychotic drugs increase the concentration of prolactin in the blood, which persists with prolonged use. Symptoms may include signs such as breast augmentation, dysmenorrhea, decreased libido, or discharge from the nipple.

    Care should be taken when administering the drug to patients receiving atropine or similar drugs, as well as in contact with phosphorus-containing insecticides (additive anticholinergic effect is possible).

    In the process of treatment should monitor the functions of the liver, kidney (with prolonged therapy), a picture of peripheral blood, an index of prothrombin. When signs or symptoms of blood dyscrasia appear, treatment should be discontinued and appropriate therapy prescribed. Treatment should also be discontinued if there are abnormalities in the liver tests, with a deviating blood urea nitrogen index. Most cases of agranulocytosis occurred between 4 and 10 weeks of therapy.During this period, patients should particularly closely monitor the appearance of sore throat or symptoms of infection. With a significant reduction in the number of leukocytes, the drug should be stopped and appropriate therapy started.

    Developing (rarely) against the background of jaundice treatment (between 2 and 4 weeks of therapy) is usually considered as a hypersensitivity reaction. The clinical picture is similar to that of infectious hepatitis, but the results of functional hepatic tests are characteristic of obstructive jaundice. Usually it is reversible, however, cases of chronic jaundice have been reported.

    Occasionally, cases of sudden death were reported in patients receiving phenothiazines. In some cases, the cause of death was cardiac arrest, in others - asphyxia due to the lack of cough reflex.

    An antiemetic effect can mask symptoms of toxicity caused by overdose of other drugs and make it difficult to diagnose diseases such as bowel obstruction, Reye syndrome, brain tumors or other encephalopathies.

    Patients with diabetes should take into account,that the carbohydrate content in one single dose of the drug (1 tablet) corresponds to: a dosage of 4 mg is 0.012 XE, a dosage of 6 mg is 0.015 XE. dosage of 10 mg is 0.018 XE.

    Caution should be exercised when using perphenazine in the elderly because they may be more sensitive to the action of the drug and the development of side effects such as extrapyramidal symptoms and tardive dyskinesia. Malignant neuroleptic syndrome (ZNS), the development of which is possible against the background of taking any classical neuroleptic drugs - a potentially fatal complex of symptoms. Diagnosis of patients with this syndrome is difficult. In differential diagnosis, it is important to identify cases in which the clinical picture includes serious medical conditions (eg, pneumonia, systemic infection, etc.), other extrapyramidal symptoms, central anticholinergic toxicity, heat stroke, drug fever, and primary pathologies of the central nervous system. Management of the NSA should include: 1) the immediate cessation of the use of antipsychotics and other medications concomitant therapy, if necessary; 2) intensive symptomatictherapy and medical control; 3) treatment of any associated serious health problems for which specific procedures are needed. There are no generally accepted specific pharmacological treatment regimens.

    It is recommended to closely monitor patients who take large doses of phenothiazine derivatives and who are undergoing surgery and interventions due to the possible development of antihypertensive effects.

    With prolonged therapy with phenothiazine derivatives, one should keep in mind the possibility of damage to the liver, cornea and the development of irreversible tardive dyskinesia. Patients who require long-term therapy should choose the minimum dose and, if possible. the shortest duration of treatment while maintaining clinical
    effectiveness. The need for continuation of treatment should be periodically reviewed.

    The simultaneous withdrawal of perphenazine therapy can lead to the development of withdrawal symptoms (dizziness, nausea, vomiting, stomach upset, trembling), so the dose should be gradually reduced until it stops completely.

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

    During the period of treatment, it is necessary to refrain from engaging in potentially dangerous activities, working with mechanisms, driving a car. perphenazine can reduce mental and / or physical performance, and also causes drowsiness (especially in the first 2 weeks of treatment).

    Form release / dosage:

    The coated tablets are 4 mg, 6 mg and 10 mg.

    For 10 tablets 4 mg or 10 mg in a contour cell package.

    5 contour squares with instructions for use are placed in a pack of cardboard.

    For the formation of military medicine kits, 6 mg of 1.2 kg in bags of polyethylene film. 2 packages of 1.2 kg per box of cardboard.

    Storage conditions:

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

    Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:P N001399 / 01
    Date of registration:17.06.2008
    The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp30.08.2015
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