Etaperazin

pharmachologic effect

Antipsychotic drug (neuroleptic), piperazine derivative of phenothiazine. It is believed that the antipsychotic effect of phenothiazines is due to the blockade of postsynaptic dopamine receptors in the mesolimbic structures of the brain. Perphenazine has a strong antiemetic effect, the central mechanism of which is associated with inhibition or blockade of dopamine D2 receptors in the chemoreceptor trigger zone of the cerebellum, and the peripheral mechanism is associated with blockade of the vagus nerve in the gastrointestinal tract. Has alpha-adrenergic blocking activity. Anticholinergic activity and sedation may occur from weak to moderate intensity, the hypotensive effect is weak. Has a pronounced extrapyramidal effect. The antiemetic effect may be enhanced by anticholinergic and sedative properties. Has a muscle-relaxing effect.

Pharmacodynamics and pharmacokinetics

The drug affects the central nervous system. This is an antipsychotic drug that has a wide spectrum of action. It has antipsychotic , antiemetic and cataleptogenic effects. In addition, the drug has alpha-adrenolytic activity. Anticholinergic and sedative effects occur to a weak or moderate extent. The hypotensive and muscle-relaxing effects are weakly expressed. The neuroleptic effect is combined with a stimulating one .

The drug is also characterized by a selective effect on deficiency symptoms. Significant extrapyramidal abnormalities are possible.

Etaperazine is well absorbed from the gastrointestinal tract. Significant fluctuations in maximum plasma . Strong binding to plasma proteins. The drug is intensively broken down, mainly in the liver. Excreted through the kidneys and with bile.

special instructions

Perphenazine should be used with caution in case of hypersensitivity to other phenothiazine drugs.

Phenothiazines are used with extreme caution in patients with pathological changes in the blood picture, liver dysfunction, alcohol intoxication, Reye's syndrome, as well as breast cancer, cardiovascular diseases, predisposition to the development of glaucoma, Parkinson's disease, gastric and duodenal ulcers , urinary retention, chronic respiratory diseases (especially in children), epileptic seizures, vomiting; in elderly patients (increased risk of excessive sedation and hypotensive effects), in depleted and weakened patients.

The development of tardive dyskinesia during the use of perphenazine is more likely in elderly patients, women and those with brain damage. Parkinsonian extrapyramidal reactions are more often observed in elderly patients, dystonic extrapyramidal reactions - in younger people. Symptoms of these disorders may occur in the first few days of treatment or after long-term therapy and may recur even after a single dose.

In case of hyperthermia, which is one of the elements of NMS, perphenazine should be discontinued immediately.

The simultaneous use of phenothiazines with absorbent antidiarrheals should be avoided.

During the treatment period, avoid drinking alcohol.

Recommendations for the use of perphenazine in children under 12 years of age have not been established. Children, especially those with acute illness, are more likely to develop extrapyramidal symptoms when using phenothiazines.

Impact on the ability to drive vehicles and operate machinery

It should be used with caution in patients engaged in potentially hazardous activities that require a high speed of psychomotor reactions.

Contraindications

The following contraindications to the use of this drug are known: progressive systemic diseases of the brain and spinal cord, cirrhosis , hemolytic jaundice , hematopoietic disorders, thromboembolic diseases, pregnancy , breastfeeding , hepatitis , nephritis , myxedema , decompensated heart disease , hypersensitivity to the active substance, late stages of bronchiectasis diseases .

Overdose

neuroleptic may occur . In such cases, the temperature often rises. coma is also possible .

The drug should be stopped immediately. Intravenous administration of Diazepam , nootropic drugs, dextrose solution , vitamins B and C is indicated. Treatment is symptomatic .

Experience of using alprazolam in complex therapy of mental disorders

Tranquilizers (benzodiazepines) constitute one of the main classes of psychotropic drugs and have been used in clinical medicine for more than 50 years.

Currently, about 30 different drugs of benzodiazepine structure (anxiolytics and hypnotics) are used. Despite the fact that in 1983 the WHO recognized the ability of benzodiazepines to cause drug dependence, they are still widely used not only in psychiatry, but also in other areas of medicine, and in a number of cases they are irreplaceable. The development of antidepressants with a pronounced anxiolytic effect (especially selective serotonin reuptake inhibitors), anxiolytics and hypnotics of non-benzodiazepine structure contributed to some displacement of benzodiazepines from medical practice, however, due to a specific mechanism of action that ensures high and rapidly developing psychotropic activity and good tolerability, they invariably occupy their niche in the treatment of mental disorders of the neurotic level.

In the spectrum of action of benzodiazepines, several main effects are traditionally distinguished: anxiolytic (anti-anxiety), sedative, hypnotic, muscle relaxant, anticonvulsant and amnestic. Currently, their anxiolytic and hypnotic effects are most important for clinical practice, while the rest are almost not used or are considered as side effects [10].

Alprazolam, a typical representative of benzodiazepine anxiolytics, has all the properties of drugs in this group to varying degrees.

The main thing for it is an anxiolytic effect. Alprazolam is a high-potency benzodiazepine, that is, a pronounced anxiolytic effect develops when using low doses of the drug. This is explained by the fact that alprazolam has a higher affinity for specific benzodiazepine receptors [1].

There are other properties that distinguish alprazolam from other representatives of this group: average duration of action, less pronounced sedation and behavioral toxicity. These features allow alprazolam to be widely used, including in outpatient practice. In addition, the ability of alprazolam to reduce the symptoms of depression is used in the treatment of mental disorders. Alprazolam is believed to be the only benzodiazepine tranquilizer that exhibits antidepressant activity [44].

The spectrum of clinical effects of alprazolam, like other benzodiazepines, is based on the modulation of GABAA receptors, followed by secondary neurochemical and hormonal changes. It is discussed that stimulation of GABA receptors leads to changes in the activity of the monoaminergic system [10]. At the same time, a weakening of the activity of the hypothalamic-pituitary-adrenal system is described [57]. Long-term use of benzodiazepines, including alprazolam, leads to a decrease in the sensitivity of GABA receptors [34]. This is the basis for the development of the phenomenon of addiction. However, it is believed that tolerance does not develop to all effects of benzodiazepines. It is unconditional regarding its hypnotic, muscle relaxant and anticonvulsant effects and is controversial regarding its anxiolytic effect [10]. Indeed, many patients take alprazolam long-term to relieve anxiety without reducing the effectiveness of treatment.

It is assumed that due to the selective effect on the α2 and α3 subunits of GABA receptors, the antidepressant effect of alprazolam is realized, which is absent in the spectrum of psychotropic activity of other tranquilizers, the action of which is associated with stimulation of GABA receptors [44].

There are interesting data on the bipolarity of the neurochemical action of alprazolam depending on the initial emotional state: in depression, the drug enhances noradrenergic activity (especially in the prefrontal cortex and hippocampus), and in anxiety it weakens it [46].

Benzodiazepines do not have an affinity for dopamine, serotonin, cholinergic, adrenergic, histamine and other receptors of the central nervous system and the autonomic nervous system. This determines the absence of side effects during their use, which are so characteristic of other classes of psychotropic drugs.

The average time to reach the maximum concentration of alprazolam in the blood is 1.5 hours [35, 36]. Due to its high lipophilicity, the drug, like other benzodiazepines, penetrates well through the blood-brain barrier, which explains the rapid onset of its therapeutic effect. Alprazolam is an intermediate-acting benzodiazepine: the average half-life of the drug is 11 hours [19].

According to various literature sources, alprazolam has a unique spectrum of psychotropic activity compared to other tranquilizers [2, 11]. The drug is most effective in the treatment of disorders, the clinical picture of which is mainly determined by anxiety symptoms of varying degrees of severity. Such conditions include, first of all, panic disorder, generalized anxiety disorder, various anxiety-depressive states, including reactive and somatogenic. In addition, alprazolam has proven itself in the treatment of obsessive-compulsive disorder, isolated phobias, and withdrawal states.

The effectiveness of alprazolam in the treatment of panic disorder is evidenced by the results of numerous comparative studies [45]. A number of studies [11] indicate that in the treatment of panic disorder, compared with other benzodiazepine tranquilizers, alprazolam significantly reduces the frequency of panic attacks and reduces the severity of anxiety and depressive symptoms. If cases of partial improvement are taken into account, alprazolam is effective in 80% of cases [9, 15]. It is believed that in this regard the effect of alprazolam is comparable only to clonazepam [7,11]. It has been established that alprazolam at an average dose of 4 to 7 mg/day. more effective than placebo during 4 weeks of observation [12]. However, there was no direct relationship between the concentration of the drug in the blood and the effectiveness of therapy. This means that the effectiveness of treatment largely depends not on the dose of the drug, but on clinical and psychopathological factors. In addition, it is indicated that the drug acts not only on anticipatory anxiety, but also on the symptoms of panic attacks themselves, reducing their severity and preventing the development of repeated panic attacks [6]. The dose range of alprazolam for the treatment of panic disorder is wider than for the treatment of other anxiety conditions, and is up to 10 mg/day. (on average 2-6 mg/day) [1.47], divided into 3-4 doses.

Numerous studies have examined the use of alprazolam for generalized anxiety disorder (GAD). The symptoms of GAD are effectively reduced by treatment with alprazolam at an average daily dosage of 0.5-4.0 mg, divided into 3-4 doses, in different age groups of patients, which is confirmed by the results of numerous placebo-controlled studies [14, 24, 25, 26, 29 ]. It has been established that, compared with other benzodiazepine tranquilizers, the use of alprazolam is accompanied by fewer side effects [6, 14, 27, 32]. It should also be noted that the effect is relatively rapid, manifesting itself already during the first week of treatment [33]. Despite the high effectiveness of alprazolam in the treatment of GAD, antidepressants are currently preferred in the treatment of this pathology [3, 48, 49]. However, even in this case, the role of benzodiazepines in the treatment of GAD cannot be underestimated. Considering the fact that the effect of antidepressants appears only several weeks after the start of therapy, the use of benzodiazepines at the beginning of treatment to relieve anxiety and insomnia does not yet have an alternative. Due to the risk of developing drug dependence, it is recommended to use alprazolam for several weeks followed by gradual withdrawal. In cases where this period is not enough to develop a lasting therapeutic effect, longer use of the drug is possible, subject to careful follow-up.

In a study of the effectiveness of alprazolam in patients with GAD manifested by irritable bowel syndrome, after 4 weeks of therapy there was a significant reduction in both anxiety symptoms (in 98% of patients) and gastrointestinal complaints (in 89% of patients) [58]. The drug has also proven itself in the treatment of anxiety in alcohol withdrawal states [40].

It is repeatedly mentioned in the literature that, in addition to the anxiolytic effect itself, the drug also has an antidepressant effect, which has not been detected in other tranquilizers [6, 17, 41,60]. Its presence was discovered shortly after the active introduction of alprazolam into clinical practice and was confirmed in a number of further studies. There are indications of the effectiveness of alprazolam not only in neurotic, but also in endogenous depression [6]. Moreover, its effect is comparable to tricyclic antidepressants [17, 39, 53, 55]. Many authors indicate the preference of its use for syndromes in the structure of which there is a combination of anxiety and depressive symptoms [4, 5,10].

There is evidence indicating the effectiveness of alprazolam in the treatment of premenstrual syndrome [30, 37].

The successful use of alprazolam in the treatment of acute stress and obsessive-compulsive disorders has been described. In this case, the drug was prescribed either at the beginning of the course in addition to selective serotonin reuptake inhibitors (SSRIs) to relieve severe anxiety, or as monotherapy in cases of resistance or intolerance to SSRIs [16, 42]. However, despite speculation, alprazolam was ineffective in the treatment of post-traumatic stress disorder (PTSD) [23].

Data have been obtained on the use of alprazolam as a corrector of extrapyramidal symptoms (especially acute dystonia and akathisia) caused by taking antipsychotics [38]. However, in the presence of other highly effective means of correcting neuroleptic syndrome, alprazolam cannot be considered as a first-line drug.

The most common side effects during therapy with alprazolam are sedation and drowsiness [31], which is explained by the interaction of the drug with GAMKA receptors and during the course of treatment the above side effects decrease significantly.

Regular use of alprazolam should be discontinued gradually to avoid the development of withdrawal syndrome. During this period, lasting from several weeks to months, the daily dosage of the drug is gradually reduced until complete discontinuation [54]. A number of studies [43, 48, 54] note that reducing the dose of benzodiazepine tranquilizers may be accompanied by withdrawal syndrome and the return of clinical manifestations of the underlying disease, especially in cases of abrupt cessation of therapy.

Despite the widespread perception of the risk of drug dependence, data from numerous studies indicate that the incidence of dependence among patients receiving alprazolam is relatively low [50, 51, 52]. The authors note that dependence on benzodiazepines is a relatively rare phenomenon and occurs mainly in individuals who abuse alcohol or drugs.

There are some other side effects of alprazolam worth mentioning. A number of studies have revealed a deterioration in the processes of perception and reproduction of new information [28, 56]. This feature must be taken into account when driving a car [18]. It is also important to note the interaction of alprazolam with alcohol, because Many patients with anxiety symptoms independently resort to drinking alcohol to alleviate their condition. Their combined use leads to a significant deterioration in results when performing psychological tests [20], and in some patients it increases aggression and irritability [21,22].

Thus, as numerous data show, including recent years, alprazolam remains a fairly popular and effective tranquilizer. However, many issues require clarification and additional study. In particular, the place of alprazolam in the complex treatment of mental disorders along with new drugs from other psychopharmacological groups needs to be considered. Questions remain not entirely clear regarding the dosages of alprazolam used, the possible duration of its use, as well as the frequency and conditions for the formation of dependence.

Purpose of the study: to analyze the use of alprazolam in the complex treatment of various mental disorders to clarify the indications for its use.

The medical histories of 124 patients who were undergoing inpatient (58 people - 46.8%) and outpatient (66 people - 53.2%) treatment in the psychiatric clinic named after. S.S. Korsakov First Moscow State Medical University named after. THEM. Sechenov and taking alprazolam at a certain stage of therapy. All patients underwent a thorough psychiatric and somato-neurological examination using the necessary paraclinical methods to assess the effectiveness of therapy and possible side effects.

Among the patients there were 74 women (59.7%) and 50 (40.3%) men aged from 26 to 70 years. The duration of the diseases ranged from 2 months to 40 years.

According to the results of the assessment of mental disorders according to ICD-10, patients were distributed as follows: schizophrenia F20 was diagnosed in 24 patients (19.4%), of which paranoid F20.0 - in 10 (8.1%), sluggish F21 - in 14 (11.3 %); affective disorders F3 - in 46 (37.2%), including a depressive episode of varying severity F32 - in 8 (6.5%), recurrent depressive disorder F33 - in 26 (21.0%), bipolar disorder F31 - in 12 (9.7%); organic brain lesions F06 - in 6 (4.8%), of which organic anxiety disorder F06.4 - in 4 (6.4%), organic personality disorder F07.0 - in 2 (1.6%); psychogenic disorders F4 - in 48 (38.7%), including panic disorder F41.0 - in 16 (12.9%), generalized anxiety disorder F41.1 - in 4 (3.2%), obsessive-compulsive disorder F42.2 - in 2 (1.6%), adaptation disorders in the form of depressive F43.21 and anxiety-depressive reaction F43.22 - in 26 (21.0%).

All patients received treatment with psychotropic drugs of various pharmacological groups in accordance with the leading psychopathological syndrome. As part of complex therapy, all patients were prescribed alprazolam as a main or auxiliary agent in a daily dose of 0.5 to 1.5 mg in 2-3 doses [1]. About half of the patients are 59 people. (47.6%) fell ill for the first time: they were diagnosed with a first-time depressive episode (8), adaptation disorders (26), neurotic anxiety-phobic disorders (14), organic disorders (4), low-grade schizophrenia (5) and paranoid schizophrenia (2 ). Before entering the clinic, these patients practically did not receive (with the exception of some recommendations from neurologists) psychotropic drugs, including tranquilizers. The remaining patients had previously taken various drugs, including benzodiazepines, but none of the patients had symptoms of established drug dependence at the time of their visit to the clinic.

When prescribing alprazolam, primarily its anxiolytic and antidepressant effects were taken into account. Weak sedative, hypnotic, muscle relaxant and amnestic effects, especially in small doses, made it possible to use it as a daytime tranquilizer in outpatients, including workers.

As is known, one of the main indications for the use of alprazolam is generalized anxiety disorder (GAD), but the diagnostic criteria for GAD are still controversial [3], and anxiety is often present in other forms of neuroses and depression. In our study, there were few patients with this diagnosis, and all of them took alprazolam in combination with SSRI antidepressants, mainly paroxetine. The anti-anxiety effect of these antidepressants is comparable to alprazolam [48], but it appears several weeks after the start of therapy. In the first weeks of treatment, anxiety may increase and sleep may be disrupted. It is during this period that the prescription of tranquilizers, and in particular alprazolam, has no alternative. The duration of treatment in patients with GAD is from two weeks to two months at an average dose of 0.75 mg per day (0.25 mg 3 times a day).

When treating patients with panic disorder, doses of up to 1 mg per day were used in 3-4 doses. The duration of therapy ranged from 3 to 8 months. Observation of patients over time shows that at first panic attacks disappear quite quickly, then the anxious anticipation of an attack gradually reduces, fears decrease and, accordingly, avoidant behavior disappears. In some cases, in the presence of symptoms of depression and in order to prevent panic attacks, antidepressants from the SSRI group, in particular Cipralex, were additionally prescribed.

For obsessive-compulsive disorder, alprazolam (dose 0.5 mg per day) was used in one case in combination with fluoxetine for 1 month, then due to insufficient effectiveness, therapy was changed. In another case, in a patient with various obsessions (fears, ideas, compulsions) in combination with panic attacks and avoidant behavior, alprazolam at a dose of up to 1.5 mg per day in combination with etaprazine up to 8 mg per day was successfully used for a long time (more 4 years) with almost complete reduction of symptoms and restoration of social functioning, in the absence of symptoms of addiction.

Patients with depressive disorders, including endogenous and neurotic depression, in our study made up more than half of all observations - 58.2%. In most cases, the structure of the depressive syndrome included symptoms of anxiety, which was an indication for the prescription of apprazolam, especially in the first weeks of therapy, before the onset of the anxiolytic effect of antidepressants. For primary depressive episodes and recurrent depression, alprazolam was used mainly as part of complex therapy along with antidepressants of various generations (maprotiline, azaphene, paroxetine, mirtazapine, Cymbalta, Valdoxan, etc.), and small doses of some antipsychotics (sulpiride). In some cases, hypnotics (zopiclone) were additionally prescribed for sleep disturbances. Treatment of depression in the context of bipolar disorder (BD) had its own characteristics, taking into account the possibility of transition to the manic phase, especially with BD-1. Antidepressants that do not cause an inversion of affect were used (azafen, valdoxan, fevarin). Already during the relief therapy, anticonvulsants (vaporates, carbamazepine) and antipsychotics (quetiapine, olanzapine) were prescribed, which the patients continued to take during the period of remission as maintenance therapy. In bipolar disorder-11, depressive symptoms were treated with antidepressants from the SSRI group, venlafaxine, valdoxan in combination with alprazolam, which has an anxiolytic effect, especially in the first weeks of therapy before the development of the antidepressants’ own effects, and potentiates their antidepressant activity [5]. Among anticonvulsants, preference was given to lamotrigine and valproic acid preparations, and among antipsychotics, preference was given to quetiapine. In almost half of the cases of neurotic depression (12 people), alprazolam was used as monotherapy, at a dose of 0.75-1 mg for 4-7 weeks with a good effect, i.e. almost complete recovery.

This once again indicates that alprazolam has an antidepressant effect.

Many patients with depression experienced symptoms of somatic anxiety (including somatized depression), which disappeared along with mental anxiety. Perhaps in this case we can talk about the vegetotropic effect of alprazolam, like other benzodiazepines (phenazepam, diazepam). Another explanation is possible: along with anxiety, its somato-vegetative “accompaniment” also goes away.

In the history of many patients with panic disorder, anxiety-phobic disorders, and recurrent depression, there were episodes of effective use of alprazolam with tianeptine with a fairly rapid reduction of symptoms and restoration of social functioning.

For organic brain lesions, alprazolam was used as an anti-anxiety and sedative in combination with small doses of sedative antipsychotics (clozapine, olanzapine), nootropics. The duration of therapy is no more than a month, daily doses are up to 0.75 mg. Antipsychotics in these cases were prescribed as behavior correctors, and alprazolam “mitigated” the side effects.

In case of sluggish schizophrenia, alprazolam was prescribed as part of a polymorphic neurosis-like syndrome, which included anxiety-phobic, panic, obsessive-compulsive and depressive disorders. As a rule, it was used in combination with antidepressants (rexetine, mirtazapine, amitriptyline), antipsychotics (sulpiride, sonapax, chlorprothixene, quetiapine), hypnotics (zopiclone, zolpidem), short courses from two to four weeks at a dose of 0.5-0. 75 mg per day.

A special group consisted of patients with paranoid schizophrenia, to whom alprazolam was prescribed in addition to antipsychotics (clozapine, olanzapine, paliperidone, risperidone) as an anti-anxiety agent and potentiating sedative effect. This made it possible to reduce doses of antipsychotics, which is especially important when conducting treatment on an outpatient basis in order to improve social adaptation and quality of life. Courses of therapy of varying durations, from two weeks to several months, depending on the indications, the dose of the drug is 1-1.5 mg per day.

Thus, the study confirmed that alprazolam has high anxiolytic activity even in small doses with insignificant sedative and hypnotic effects, which allows its use as a daytime tranquilizer and anxiolytic in patients with a wide range of anxiety-phobic and panic disorders of various origins. Alprazolam differs favorably from other benzodiazepines by having an antidepressant effect, so it can be used to treat not only anxiety, but also depressive disorders. There is good tolerability and high safety of the drug, as well as a virtual absence of the risk of drug dependence when using small doses and strictly observing the indications for use. Alprazolam can be prescribed in inpatient and outpatient settings, both in short courses and long-term, depending on the nature of mental disorders.

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Experience of alprazolam usage in a complex therapy of psychiatric disorders.

NA Tuvina, DS Danilov, VV Balabanova, SV Prochorova, IG Korobkova

Department of Psychiatry and Addiction

IM Sechenov First Moscow State Medical University

SUMMARY : Literary data, defining the peculiarities of alprazolam action, its psychotropic effects, tolerability, the possibility of its usage in various psychiatric disorders proven by numerous studies, were analyzed. Our own experience of alprazolam use, mainly in combination with drugs of other psychopharmacological groups [antidepressants, neuroleptics, anticonvulsants] in the treatment of psychiatric disorders: depressions of various genesis, disorders of anxiety and phobic spectrum, obsessions were represented. 124 psychiatric in- and outpatients showed high efficacy and good tolerability of small daily doses of alprazolam and the absence of dependence and withdrawal syndrome.

KEY-WORDS : alprazolam, panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, acute stress disorder, schizophrenia, affective disorder.

CONTACT : NA Tuvina ( [email protected] ].

Interaction

Suppression of the nervous and respiratory systems increases when combined with drugs that depress the nervous system, as well as ethanol-containing drugs and ethanol .

Combination with drugs that provoke extrapyramidal reactions increases the number and frequency of extrapyramidal disorders. Fluoxetine can also cause extrapyramidal symptoms and dystonia .

Anticonvulsants may lower the seizure threshold , and medications to treat hyperthyroidism , in turn, increase the likelihood of agranulocytosis .

Interaction with drugs that cause hypotension may cause orthostatic hypotension .

Combination with drugs that have anticholinergic effects may lead to an increase in anticholinergic effect, and the antipsychotic effect of the antipsychotic may be reduced.

Concomitant use of Etaperazine with MAO inhibitors , tricyclic antidepressants and Maprotiline increases the likelihood of developing NMS . And combination with antacids , lithium salts and antiparkinsonian drugs interferes with the absorption of phenothiazines .

Interactions with amphetamines , clonidine , Epinephrine , Levodopa and Guanethidine may reduce their effect.

Combination with Ephedrine may weaken its vasoconstrictor effect.

Side effects

From the central nervous system: drowsiness, akathisia, blurred vision, dystonic extrapyramidal reactions, parkinsonian extrapyramidal reactions.

From the liver: rarely - cholestatic jaundice.

From the hematopoietic system: rarely - agranulocytosis.

Metabolic disorders: rarely - heat stroke, melanosis.

Allergic reactions: rarely - skin rash accompanied by contact dermatitis.

Dermatological reactions: rarely - photosensitivity.

Effects due to anticholinergic action: possible dry mouth, accommodation disturbances, constipation, difficulty urinating.

Etaperazine price, where to buy

Tablets of 10 mg (50 pieces in a package) cost approximately 300 rubles. And the price of Etaperazine in 4 mg tablets (50 pieces in a package) is about 270 rubles.

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Dosage

For adults and children over 12 years of age, when taken orally, the daily dose is 4-80 mg. In the chronic course of the disease and in resistant cases, the daily dose can be increased to 150-400 mg. The frequency of administration and duration of treatment are determined individually.

For adults and children over 12 years of age, with intramuscular administration, a single dose is 5-10 mg. For intravenous administration, a single dose is 1 mg.

Maximum doses: adults and children over 12 years of age with intramuscular administration - 15-30 mg/day, with intravenous administration - 5 mg/day.