Atarax (Hydroxyzine hydrochloride) - instructions: indications, contraindications, side effects

pharmachologic effect

A derivative of diphenylmethane, it has moderate anxiolytic activity;
It also has a sedative, antiemetic, antihistamine and m-anticholinergic effect. Blocks central m-cholinergic receptors and histamine H1 receptors and inhibits the activity of certain subcortical zones. Does not cause mental dependence or addiction. The clinical effect occurs 15-30 minutes after taking the drug orally. Has a positive effect on cognitive abilities, improves memory and attention. Relaxes skeletal and smooth muscles, has bronchodilator and analgesic effects, and a moderate inhibitory effect on gastric secretion. Hydroxyzine significantly reduces itching in patients with urticaria, eczema and dermatitis. With long-term use, there was no withdrawal syndrome or deterioration of cognitive functions. Polysomnography in patients with insomnia and anxiety clearly demonstrates an increase in sleep duration and a decrease in the frequency of night awakenings after a single or repeated dose of hydroxyzine at a dose of 50 mg. A decrease in muscle tension in patients with anxiety was noted when taking the drug at a dose of 50 mg 3 times a day.

Atarax for anxiety disorders (review)

Ryabokon I.V.

Anxiety is a state of fear and anxiety experienced by a person in anticipation of trouble. The causes of anxiety are varied: emotional instability, a sharp change in living conditions, the upcoming completion of a difficult task, etc. Anxiety may arise due to anticipation of a future threat (punishment or loss of loved ones). Typically, anxiety leads to defensive reactions. Anxiety is the result of frustration or its anticipation and is the primary psychological manifestation of stress. Z. Freud considered anxiety as a symptomatic manifestation of an internal emotional conflict caused by the fact that a person unconsciously suppresses sensations, feelings or impulses that are too threatening or irritating for him. With the emergence of anxiety, behavioral activity increases, the very nature of behavior changes, and additional physiological mechanisms of adaptation to changed conditions are activated.

Anxiety is a person’s tendency to experience a state of anxiety. Most often, a person’s anxiety is associated with the expectation of social consequences of his success or failure. Anxiety and anxiety are closely related to stress. On the one hand, anxious emotions are symptoms of stress. On the other hand, the initial level of anxiety determines individual sensitivity to stress. Like stress in general, the state of anxiety cannot be called unequivocally bad or good.

In other cases, anxiety is unnatural, pathological, inadequate, harmful. It becomes chronic, constant and begins to appear not only in stressful situations, but also for no apparent reason. Then anxiety not only does not help the person, but, on the contrary, begins to interfere with him in his daily activities.

The line between a “normal” stress response and a pathological anxiety disorder is often quite blurred, and it is difficult for a person to know when to seek professional help. These subsyndromal anxiety disorders are the most difficult to diagnose and often remain untreated, while having an extremely negative impact on the quality of life of the patient and those around him. It is believed that treatment options should be considered when anxiety about everyday events is beyond the patient's control. The following disorders may also be the reason for prescribing therapy: nervousness, fussiness, impaired concentration, irritability, sleep disturbance, symptoms of autonomic dysfunction.

In everyday medical practice, various herbal medicines, tranquilizers, barbiturates, antidepressants, and some antipsychotics are used to treat anxiety disorders.

One of the most powerful and quickly relieving sleep disorders and anxiety are benzodiazepine drugs. Among the disadvantages of treatment with benzodiazepines, the following should be mentioned: withdrawal syndrome (rapid resumption or transient increase in symptoms after discontinuation of the drug), the risk of addiction and the formation of drug dependence, impaired cognitive functions (attention, concentration, memory), and impaired coordination. Therefore, benzodiazepine drugs are not recommended to be taken for more than 2 weeks.

Hydroxyzine (Atarax) is neither a benzodiazepine nor a phenothiazine. The non-benzodiazepine anxiolytic Atarax (hydroxyzine) is a derivative of diphenylmetane, an antagonist of histamine H1 receptors.

Hydroxyzine is one of the oldest psychotropic drugs; it was introduced into clinical practice back in 1955. Atarax has a pronounced anti-anxiety, antihistamine, antipruritic and antiemetic effect. By reducing the concentration of histamine at the central level, it has the property of reducing anxiety, reducing aggressiveness and causing a persistent anxiolytic effect [2]. The drug acts within 15–30 minutes after oral administration (Cmax is noted 2 hours after taking the drug) and maintains this effect for 6–8 hours. Its main advantages are the absence of the “rebound” phenomenon, addiction (dependence), withdrawal symptoms and positive effect on cognitive function.

Hydroxyzine has been successfully used in a variety of areas of medicine: as a means of controlling tobacco smoking [3]; in pediatric dentistry [4]; for its intended purpose – for the treatment of anxiety neurosis (even in the era of the existence of such a nosological form) and for “mild” depression [5]; for behavioral and learning disorders in children [6]. Due to its antihistamine properties, hydroxyzine was used in allergology, to treat itching [7], and for urticaria pigmentosa (mastocytosis) in children [8]; in oncology [9]; in burn patients [10], in narcology [11] and in many other conditions.

Recently, there has been interest among researchers in the use of hydroxyzine in patients with generalized anxiety disorder (GAD). The prevalence of this pathology and the associated burden of social consequences in the current scientific literature appear to be quite significant. According to one review [E.G. Starostina. Generalized anxiety disorder and anxiety symptoms in general medical practice. Rus. honey. magazine 2004; 22 (222), 12: 1277] with reference to numerous foreign works, “GAD is among the top ten diseases with the greatest temporary disability and according to this indicator is on a par with coronary artery disease, diabetes, joint diseases, peptic ulcers, and mental disorders – with depression or even ahead of it.”

In a double-blind, placebo-controlled RCT for the treatment of GAD [17], the anxiolytic activity of Atarax at a dose of 50 mg (in 3 doses of 12.5 mg in the morning and afternoon plus 25 mg in the evening) was shown, which was manifested in a statistically significant, rapid and significant decrease symptoms of anxiety already at the end of the 1st week of treatment, which persisted for another 1 week after cessation of treatment (n=110; course duration 4 weeks; Hamilton-A score). In this case, there was no phenomenon of “rebound” or return of anxiety.

In another double-blind multicenter RCT [18], in which, along with placebo control, the benzodiazepine drug bromazepam was also used, it was shown that hydroxyzine used for 3 months was statistically significantly different from placebo and was as effective as the comparison drug. Moreover, with benzodiazepine, side effects of severe drowsiness were observed twice as often as with hydroxyzine (n = 334; dose of hydroxyzine 50 mg/day in 3 divided doses; bromazepam - 6 mg/day in 3 divided doses; improvement on the Hamilton-A scale >50 %; p<0.03 at the end of the 6th week and p<0.001 - after 12 weeks; the number of patients who responded to treatment: 40% at the 6th and 60% at the 12th week, respectively).

Another study [19] showed the effectiveness of Atarax (50 mg in 3 doses), comparable to that of the control buspirone (20 mg in 3 doses), with a statistically significant difference between Atarax and placebo on the 28th day of treatment (p<0.015) . There was no rebound phenomenon with abrupt withdrawal of both drugs (n=244; age 18–65 years).

In addition, one of the advantages of hydroxyzine is that, unlike benzodiazepines, it does not depress cognitive abilities [20] (triple crossover, double-blind RCT; comparing a single dose of 50 mg of hydroxyzine with a single dose of 2 mg of lorazepam and placebo; n = 9; healthy volunteers; 3-day interval before cross-over; assessment of cognitive functions 2–5 hours after taking comparator drugs).

Some studies have shown a positive effect of hydroxyzine on cognitive function [21] (comparison with lorazepam; double-blind multicenter RCT; n=30; GAD, Atarax 100 mg in 3 divided doses, lorazepam 4 mg in 3 divided doses; Beck score 28– th day of treatment). Unlike lorazepam, with the same anxiolytic activity, hydroxyzine restored cognitive function to normal limits.

Similar results were obtained in another, less conclusive study - an open RCT (A.E. Bobrov et al. Journal of Neurology and Psychiatry named after S.S. Korsakov. 1988; 2. GAD; n=50; outpatients; treatment course is 4 weeks, plus 2 weeks of follow-up).

Considering the characteristics of the drug (quick onset of action, good tolerability), lack of dependence and depression of the central nervous system make it an alternative drug to benzodiazepines in children and adolescents. In a study conducted at the Children's Psychiatry Center [23], Atarax was prescribed for various forms of mental illness in children and adolescents with manifestations of anxiety, irritability and insomnia-type sleep disorders, and its effectiveness was assessed. The study included 50 patients aged 5 to 18 years with various forms of mental illness, who were undergoing outpatient observation and treatment at the Children's Psychiatry Center. At the end of the 4th week of therapy, there was a decrease in the manifestations of anxiety and various fears noted earlier: falling asleep in the dark, staying at home in the absence of parents, fears of animals, noise of household appliances; in one case, a five-year-old boy could stay at home with a nanny without his parents (he had previously shown a pronounced affective reaction). In addition, all patients' sleep improved already in the second week of therapy, tearfulness, moodiness, and irritability were reduced. Simultaneously with the reduction of anxiety, the mood improved in 7 patients with a mixed anxious and depressive reaction caused by an adaptation disorder and with a mixed anxiety and depressive disorder, which was associated not with the direct antidepressant effect of Atarax, but with the comorbid dependence of anxiety and depression: anxiety was reduced - depression went away.

In a comparative study [22] of etifoxine and Atarax (hydroxyzine), the compared anxiolytics demonstrated high effectiveness in a wide range of psychopathological manifestations of adjustment disorders and generalized anxiety disorder. The results of therapy with etifoxine and Atarax showed the comparability of the clinical effect of the compared drugs, confirmed by a number of formalized indicators. The proportions of responders were comparable: 73.3 and 53.3% in the HARS assessment; 66.7 and 53.3% - as assessed by CGI-S for the groups receiving etifoxine and Atarax. The main clinical effect of the drugs in both groups was a decrease in the severity of manifestations of mental anxiety: the symptoms of internal tension (ethifoxine - in the 2nd week, Atarax - in the 3rd week), reactive (emotional) lability (one of the sub-items of “depressive mood”) were most quickly reduced "). In general, similar dynamics of cognitive anxiety were observed in both groups.

To summarize, we can reiterate that hydroxyzine (Atarax) has shown clear advantages over benzodiazepine anxiolytics in the treatment of anxiety disorders. Being as therapeutically effective as benzodiazepine anxiolytics, it does not produce rebound effects, does not depress cognitive function, and does not cause pathological dependence.

Literature:

1. Psychotropics 2000/2001 Lundbeck.

2. Krebs MO. Le trouble anxieux: cliniqu et implicacion neurobiologiques. La Revfue des Entretiens de Bichat 2001; 2 (5).

3. Turle G. An investigation into the therapeutic action of hydroxyzine/Atarax in the treatment of nervous disorders and the control of tobacco-habit. Brit J Psychiat 1958; 104: 82 rub. 33.

4. Lang L. An evaluation of the efficacy of hydroxyzine (atarax–vistaril) in controlling the behavior of child patients. J-Dent-Child 1965; 32, 4: 253–8)

5. R.Middlefell, K.Edwards Hydroxyzine/Atarax in the relief of tension associated with anxiety neurosis and mild depressive states. Brit J Psychiat 1959; 105:792–4.

6. Segal L, Tansley A. A clinical trial with Hydroxyzine (Atarax) on a group of maladjusted educationally subnormal children. J Mental–Science; Br J Psychiat from 1963; 1957; 103:677–81.

7. Rhoades R, Leifer K, Cohan R, Wittig H. Suppression of histamine-induced pruritus by three antihistaminic drugs. J Allergy Clin Immunol, 1975 Mar.; 55, 3: 180–5.

8. Kettelhut B, Berkebile C, Bradley D, Metcalfe D. A double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine in the treatment of pediatric mastocytosis. J Allergy Clin Immunol 1989 May; 83, 5: 866–70)

9. Broder L, Lean N, Hilsenbeck S. A randomized blinded clinical trial comparing delta–9–tetrahydrocannabinol (THC) and hydroxizine (HZ) as antiemetics (AE) for cancer chemotherapy (CT). PROC–AM–ASSOC–CANCER–RES; 1982; 23:514.

10. Vitale M, Fields–Blache C, Luterman. A Severe itching in the patient with burns. J burn care & rehabilitation 1991; 12, 4: 330–3.

11. Kaim S, Klett C, B. Rothfeld. Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Agressologie: revue internationale de physio-biologie et de pharmacologie appliquees aux effets de l'agression, 1968; 9, 2: 305–8.

12. Chignon G. Le trouble Anxiete Generalise: du probleme diagnostique au defi therapeutique. Nervure J psychiat 1988; 11 (suppl.): 1–16.

13. Wittchen H–U, Jakobi F. Size and burden of mental disorders in Europe – a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15: 357–76; For details, see the February issue of our magazine).

14. Goodwin R, Gorman J. Psychopharmakologic Treatment of generalized anxiety disorder and risk of major Depression. Am J Psychiat 2002; 159:1935–7.

15. Goodwin RD, Jack M. Gorman. Treatment of generalized anxiety disorder with psychotropic drugs and the risk of major depressive disorder

16. Martin P. Coprescription, Antidepresseurs et anxiolytiques: consequences pratiques de la meilleure connaissance desmecanismes d'action putatifs des anxiolytiques. Actuel Psychiat 2001; 19 (1/2): 2–7.

17. Ferreri M, Hantouche T, M. Billardon. Interet de l'hydroxizyne dans des troubles d'anxiete generalisee: etude controlee en double aveugle versus placebo. L'encephale 1994; 20: 785–91.

18. Llorka P. et al. Efficiency and safety of hydroxysyne in the treatment of generalized anxiety disorder: a 3-month double-blind study. J Clin Psychiatry 2002; 63:1020–7.

19. Lader Scotto J. A multicenter double–blind comparison of hydroxizine, buspirone and placebo in patient with generalized anxiety disorder. Psychopharmacology 1998; 139:402–6.

20. De Brabander A, Deberdt W. Effect of hydroxizyne on attention and memory. Human Psychopharmacology 1990; 357–62.

21. Samuelian J, Billardon M, Guillou N. Retentissment sur les functions cognitives de deux traits anxiolitiques chez des patients souffrant d'anxiete generalisee. L'encephale 1995; 21:147

22. Andryushchenko A.V., Beskova D.A., Romanov D.V. Psychopharmacotherapy of generalized anxiety (experience with the use of Strezam and Atarax) Mental disorders in general medicine No. 1; pp. 33–36

23. Rezakov A.A. Experience of using hydroxyzine (atarax) in children and adolescents. "PHARMIndex-Practik" issue 10; 2006, pp.37–39

Pharmacokinetics

Suction

Hydroxyzine is highly absorbed from the gastrointestinal tract. Cmax is observed 2 hours after taking the drug.

After a single dose of the drug in a single dose of 25 mg or 50 mg in adults, the plasma concentration is 30 ng/ml and 70 ng/ml, respectively.

Bioavailability when taken orally and intramuscularly is 80%.

Distribution

Hydroxyzine is more concentrated in tissues (particularly skin) than in plasma. The distribution coefficient is 7-16 l/kg.

Hydroxyzine penetrates the BBB and the placental barrier, concentrating more in the fetal tissues than in the mother's body. Metabolites are found in breast milk.

Metabolism and excretion

Hydroxyzine is metabolized in the liver. The main metabolite (45%) is cetirizine, which is a histamine H1 receptor blocker. The total clearance of hydroxyzine is 13 ml/min/kg. T1/2 in adults is 14 hours. Only 0.8% of hydroxyzine is excreted unchanged in the urine.

Pharmacokinetics in special clinical situations

In children, the total clearance is 4 times less than in adults, T1/2 in children aged 14 years is 11 hours, in children aged 1 year - 4 hours.

In elderly patients, T1/2 is 29 hours, the distribution coefficient is 22.5 l/kg.

In patients with impaired liver function, T1/2 increases to 37 hours, the concentration of metabolites in the blood serum is higher than in young patients with normal liver function. The antihistamine effect can last for 96 hours.

Anti-anxiety effectiveness of Atarax

Sometimes anxiety is natural, adequate, and useful. Everyone feels anxious, restless or stressed in certain situations, especially if they have to do something unusual or prepare for it. For example, giving a speech in front of an audience or passing an exam. A person may feel anxious when walking down an unlit street at night, or when lost in a strange city. This type of anxiety is normal and even useful, as it prompts you to prepare a speech, study the material before an exam, and think about whether you really need to go out at night all alone. In other cases, anxiety is unnatural, pathological, inadequate, harmful. It becomes chronic, constant and begins to appear not only in stressful situations, but also for no apparent reason. Then anxiety not only does not help the person, but, on the contrary, begins to interfere with him in his daily activities. The line between a “normal” stress response and a pathological anxiety disorder is often quite blurred, and it is difficult for a person to know when to seek professional help. These subsyndromal anxiety disorders are the most difficult to diagnose and often remain untreated, while having an extremely negative impact on the quality of life of the patient and those around him. It is believed that treatment options should be considered when anxiety about everyday events is beyond the patient's control. The following disorders may also be a reason for prescribing therapy: nervousness, fussiness, impaired concentration, irritability, sleep disturbance, symptoms of autonomic dysfunction. The main approaches to the treatment of anxiety disorders are: • psychotherapy • pharmacotherapy For treatment purposes, you can use simple relaxation methods (muscle relaxation, calm breathing, distraction). Friendly and encouraging conversation also helps improve the condition. The main groups of drugs for the treatment of anxiety disorders: • Benzodiazepine tranquilizers • Antidepressants: – selective serotonin reuptake inhibitors, – tricyclic antidepressants • Neuroleptics • Non-benzodiazepine tranquilizers Benzodiazepines – quickly relieve sleep disorders and anxiety symptoms. Among the disadvantages of treatment with benzodiazepines, the following should be mentioned: “recoil” syndrome (rapid resumption or transient increase in symptoms after discontinuation of the drug), the risk of addiction and the formation of drug dependence, impaired cognitive functions (attention, concentration, memory), and impaired coordination. Therefore, drugs of the benzodiazepine group should not be taken for more than 2–4 weeks. Tricyclic antidepressants are powerful drugs that effectively relieve all anxiety and depressive symptoms (affecting both physical and mental manifestations of anxiety) and sleep disorders. Can be used for long-term treatment and prevention of anxiety. Tricyclic antidepressants have more pronounced side effects (dry mucous membranes, constipation, cardiovascular disorders, transient cognitive impairment). This worsens tolerability and increases the list of contraindications for their use in the treatment of anxiety, especially in patients with concomitant somatic diseases. Selective serotonin reuptake inhibitors are relatively safe, have a minimal range of side effects, are not addictive, and therefore can be used as long-term maintenance treatment. Their relative disadvantage is the long “waiting” period before the onset of the clinical effect of the drug (from 2 to 4 weeks). In addition, antidepressants in this group have side effects such as increased appetite and weight gain, nausea, loose stools, constipation, sweating, sleep disturbances, and sexual functions (libido and orgasm). In some cases, a positive effect in the treatment of anxiety is achieved with the use of antipsychotics. Typically, small doses of these drugs are used. However, when antipsychotics are prescribed, weakness, decreased blood pressure, menstrual irregularities, weight gain, colostrum secretion, and decreased libido may occur. Finally, international recommendations list another drug for the treatment of anxiety – hydroxyzine (Atarax). It is characterized by a rapid onset of effect, absence of addiction and drug dependence, does not impair cognitive functions, and has antipruritic and antiemetic effects. Hydroxyzine is neither a benzodiazepine nor a phenothiazine. The non-benzodiazepine anxiolytic Atarax (hydroxyzine) is a derivative of diphenylmetane, an antagonist of histamine H1 receptors. Hydroxyzine has been successfully used in a variety of areas of medicine: as a means of controlling tobacco smoking [1]; in pediatric dentistry [2]; for its intended purpose – for the treatment of anxiety neurosis (even in the era of the existence of such a nosological form) and for “mild” depression [3]; for behavioral and learning disorders in children [4]. Due to its antihistamine properties, hydroxyzine was used in allergology, to treat itching [5], and for urticaria pigmentosa (mastocytosis) in children [6]; in oncology [7]; in burn patients [8], in narcology [9] and in many other conditions. Recently, there has been interest among researchers in the use of hydroxyzine in patients with generalized anxiety disorder (GAD). The prevalence of this pathology and the associated burden of social consequences in the current scientific literature appear to be quite significant. According to one review [E.G. Starostina. Generalized anxiety disorder and anxiety symptoms in general medical practice. Rus. honey. magazine 2004; 12, 22 (222): 1277], with reference to numerous foreign works, “GAD is among the top ten diseases with the greatest temporary disability and according to this indicator is on the same level with ischemic heart disease, diabetes, joint diseases, peptic ulcer disease, and among mental disorders – with depression or even ahead of it.” In a double-blind, placebo-controlled study for the treatment of generalized anxiety disorder [10], the anxiolytic activity of Atarax at a dose of 50 mg (in 3 doses of 12.5 mg in the morning and afternoon plus 25 mg in the evening) was shown, which was manifested in a statistically significant, rapid and a significant reduction in anxiety symptoms already at the end of the 1st week of treatment, which persisted for another 1 week after cessation of treatment (n=110; course duration 4 weeks; Hamilton scale score - A). In this case, there was no phenomenon of “rebound” or return of anxiety. In another double-blind multicenter study [11], in which, along with placebo control, the benzodiazepine drug Bromazepam was also used, it was shown that hydroxyzine used for 3 months was statistically significantly different from placebo and was as effective as the comparison drug . Moreover, with benzodiazepine, side effects of severe drowsiness were observed twice as often as with hydroxyzine (n = 334; dose of hydroxyzine 50 mg/day in 3 divided doses; bromazepam - 6 mg/day in 3 divided doses; improvement on the Hamilton-A scale >50 %; p<0.03 at the end of the 6th week and p<0.001 - after 12 weeks; the number of patients who responded to treatment: 40% at the 6th and 60% at the 12th week, respectively). Another study [12] showed the effectiveness of Atarax (50 mg in 3 doses), comparable to that of the control buspirone (20 mg in 3 doses), with a statistically significant difference between Atarax and placebo on the 28th day of treatment (p <0.015) . There was no rebound phenomenon with abrupt withdrawal of both drugs (n=244; age 18–65 years). Another advantage of hydroxyzine is that, unlike benzodiazepines, it does not depress cognitive abilities [13] (triple crossover, double-blind clinical trial; comparing a single dose of 50 mg of hydroxyzine with a single dose of 2 mg of lorazepam and placebo; n = 9; healthy volunteers; 3-day interval before cross-over; assessment of cognitive functions 2-5 hours after taking comparator drugs). Some studies have shown a positive effect of hydroxyzine on cognitive function [14] (comparison with lorazepam; double-blind multicenter clinical trial; n = 30; GAD, Atarax 100 mg in 3 divided doses, lorazepam 4 mg in 3 divided doses; Beck score 28 -th day of treatment). Unlike lorazepam, with the same anxiolytic activity, hydroxyzine restored cognitive function to normal limits. Similar results were obtained in another, less evidence-based study - an open RCT [A.E. Bobrov et al. Journal neurol. and psychiatrist. them. S.S. Korsakov. 1988; 2] outpatients with GAD; (n=50). The course of treatment is 4 weeks, plus 2 weeks of follow-up. Features of Atarax - rapid onset of action, good tolerability, lack of dependence and depression of the central nervous system, make it an alternative drug to benzodiazepines in children and adolescents. In a study conducted at the Children's Psychiatry Center [15], Atarax was prescribed for various forms of mental illness in children and adolescents with symptoms of anxiety, irritability and insomnia-type sleep disorders, and its effectiveness was assessed. The study included 50 patients aged 5 to 18 years with various forms of mental illness, who were undergoing outpatient observation and treatment at the Children's Psychiatry Center. At the end of the 4th week of therapy, there was a decrease in the manifestations of anxiety and various fears noted earlier - falling asleep in the dark, staying at home in the absence of parents, fears of animals, noise of household appliances. In one case, a 5-year-old boy could stay at home with a nanny without his parents - a pronounced affective reaction was previously noted. In addition, all patients' sleep improved already in the second week of therapy, tearfulness, moodiness, and irritability were reduced. Simultaneously with the reduction of anxiety, the mood improved in 7 patients with a mixed anxious and depressive reaction caused by an adaptation disorder and with a mixed anxiety and depressive disorder, which was associated not with the direct antidepressant effect of Atarax, but with the comorbid dependence of anxiety and depression: anxiety was reduced - depression went away. Hydroxyzine (Atarax) has its obvious advantages over benzodiazepine anxiolytics in the treatment of anxiety disorders; it does not produce “rebound” phenomena, does not depress cognitive function and does not cause pathological dependence. References 1. Turle G. An investigation into the therapeutic action of hydroxyzine/Atarax in the treatment of nervous disorders and the control of tobacco–habit. Brit J Psychiat 1958; 104: 82 rub. 33. 2. Lang L. An evaluation of the efficacy of hydroxyzine (atarax–vistaril) in controlling the behavior of child patients. J–Dent–Child 1965; 32, 4: 253–8) 3.R.Middlefell, K.Edwards Hydroxyzine/Atarax in the relief of tension associated with anxiety neurosis and mild depressive states. Brit J Psychiat 1959; 105:792–4. 4. Segal L, Tansley A. A clinical trial with Hydroxyzine (Atarax) on a group of maladjusted educationally subnormal children.J Mental–Science; Br J Psychiat from 1963; 1957; 103:677–81. 5. Rhoades R, Leifer K, Cohan R, Wittig H. Suppression of histamine-induced pruritus by three antihistaminic drugs. J Allergy Clin Immunol, 1975 Mar.; 55, 3: 180–5. 6. Kettelhut B, Berkebile C, Bradley D, Metcalfe D. A double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine in the treatment of pediatric mastocytosis. J Allergy Clin Immunol 1989 May; 83, 5: 866–70) 7. Broder L, Lean N, Hilsenbeck S. A randomized blinded clinical trial comparing delta–9–tetrahydrocannabinol (THC) and hydroxizine (HZ) as antiemetics (AE) for cancer cancer (CT). PROC–AM–ASSOC–CANCER–RES; 1982; 23: 514. 8. Vitale M, Fields–Blache C, Luterman. A Severe itching in the patient with burns. J burn care & rehabilitation 1991; 12, 4: 330–3. 9. Kaim S, Klett C, B. Rothfeld. Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Agressologie: revue internationale de physio-biologie et de pharmacologieappliquees aux effets de l'agression, 1968; 9, 2: 305–8. 10. Ferreri M, Hantouche T, M. Billardon. Interet de l'hydroxizynedans des troubles d'anxiete generalalisee: etude controlee en double aveugle versus placebo. L'encephale 1994; 20: 785–91. 11. Llorka P. et al. Efficiency and safety of hydroxysyne in the treatment of generalized anxiety disorder: a 3–month double–blind study. J Clin Psychiatry 2002; 63:1020–7. 12. Lader Scotto J. A multicenter double–blind comparison of hydroxizine, buspirone and placebo in patient with generalized anxiety disorder. Psychopharmacology 1998; 139:402–6. 13. De Brabander A, Deberdt W. Effect of hydroxizyne on attention and memory. Human Psychopharmacology 1990; 357–62. 14. Samuelian J, Billardon M, Guillou N. Retentissmentsur les functions cognitives de deuxtraitmentsanxiolitiques chez des patients souffrantd'anxietegeneralisee. L'encephale 1995; 21: 147 15. Rezakov A.A. Experience of using hydroxyzine (atarax) in children and adolescents. “PHARMIndex-Practik” issue 10; 2006, pp. 37–39

Indications

- adults: for the relief of anxiety, psychomotor agitation, feelings of internal tension, increased irritability in neurological, mental (including generalized anxiety, adaptation disorders) and somatic diseases, chronic alcoholism; withdrawal syndrome in chronic alcoholism, accompanied by psychomotor agitation;

- as a sedative during premedication;

- skin itching (as symptomatic therapy).

Contraindications

- porphyria;

- pregnancy;

- period of labor;

- lactation period (breastfeeding);

- hypersensitivity to the components of the drug;

- hypersensitivity to cetirizine and other piperazine derivatives, aminophylline or ethylenediamine.

It is not recommended to prescribe Atarax tablets to patients with hereditary galactose intolerance, as well as impaired absorption of glucose and galactose, because The tablets contain lactose.

The drug should be prescribed with caution for myasthenia gravis, prostatic hyperplasia with clinical manifestations, difficulty urinating, constipation, increased intraocular pressure, dementia, and a tendency to seizures; with a predisposition to the development of arrhythmia; with simultaneous use of drugs that have arrhythmogenic effects; simultaneously with other CNS depressants or anticholinergics (dose reduction required). A reduction in the dose of the drug is required in patients with severe and moderate renal failure, with liver failure, and in elderly patients with decreased glomerular filtration.

Dosage

The drug is taken orally.

For the symptomatic treatment of itching in children aged 12 months to 6 years, the drug is prescribed in a daily dose of 1-2.5 mg/kg body weight in several doses; children over 6 years of age - at a dose of 1-2 mg/kg/day in several doses.

For premedication in children, the drug is prescribed at a dose of 1 mg/kg body weight 1 hour before surgery, and additionally the night before surgery.

For the symptomatic treatment of anxiety, adults are prescribed a dose of 25-100 mg/day in several doses during the day or at night. The average dose is 50 mg/day (12.5 mg in the morning, 12.5 mg in the afternoon and 25 mg at night). If necessary, the dose can be increased to 300 mg/day.

For the symptomatic treatment of itching, the initial dose is 25 mg; if necessary, the dose can be increased 4 times (25 mg 4 times a day).

The maximum single dose should not exceed 200 mg, the maximum daily dose is no more than 300 mg.

In elderly patients, the initial dose should be reduced by 2 times.

Patients with moderate to severe renal insufficiency, as well as hepatic insufficiency, require a dose reduction.

Atarax, tablets 25 mg, 25 pcs.

Manufacturer

USB Pharma S.A., Belgium

Compound

1 tablet: - hydroxyzine hydrochloride 25 mg
Excipients:

microcrystalline cellulose (Avicel PH102®),

colloidal silicon anhydride (Aerosil 200®),

magnesium stearate,

lactose monohydrate,

Opadry® Y-1-7000 (titanium dioxide, hydroxypropyl methylcellulose 2910 5cP, macrogol 400).

pharmachologic effect

Pharmgroup:

anxiolytic (tranquilizer).

Pharmaceutical action

A derivative of diphenylmethane, it has moderate anxiolytic activity; It also has a sedative, antiemetic, antihistamine and m-anticholinergic effect.

Blocks central m-cholinergic and H1-histamine receptors and inhibits the activity of certain subcortical zones. Does not cause mental dependence or addiction. The clinical effect occurs 15–30 minutes after ingestion of the tablets. Has a positive effect on cognitive abilities, improves memory and attention. Relaxes skeletal and smooth muscles, has bronchodilator and analgesic effects, and a moderate inhibitory effect on gastric secretion. Hydroxyzine significantly reduces itching in patients with urticaria, eczema and dermatitis.

With long-term use, there was no withdrawal syndrome or deterioration of cognitive functions. Polysomnography in patients with insomnia and anxiety clearly demonstrates an increase in sleep duration and a decrease in the frequency of night awakenings after taking hydroxyzine once or repeatedly at a dose of 50 mg. A decrease in muscle tension in patients with anxiety was noted when taking the drug at a dose of 50 mg 3 times a day.

Indications

- adults for the relief of anxiety, psychomotor agitation, feelings of internal tension, increased irritability in neurological, mental (generalized anxiety and adaptation disorder) and somatic diseases, as well as in chronic alcoholism, alcohol withdrawal syndrome, accompanied by symptoms of psychomotor agitation;

- as a sedative during premedication;

- symptomatic treatment of itching.

Contraindications

hypersensitivity to any of the components of the drug Atarax, cetirizine and other piperazine derivatives, aminophylline or ethylenediamine; porphyria; pregnancy; period of childbirth; breastfeeding period. hereditary galactose intolerance, impaired absorption of glucose-galactose (since the tablets contain lactose).

With caution: myasthenia gravis; prostatic hyperplasia with clinical manifestations, incl. difficulty urinating, constipation; increased intraocular pressure; dementia; tendency to seizures; patients prone to arrhythmia or receiving drugs that can cause arrhythmia; patients simultaneously receiving treatment with other CNS depressants or anticholinergic drugs (the dose should be reduced); patients with severe and moderate severity of renal failure, as well as liver failure (dose reduction is necessary); elderly patients (the dose is reduced in case of reduced glomerular filtration.

Side effects

They are mild and transient, usually disappearing within a few days of starting treatment or after reducing the dose.

Side effects are mainly related to CNS depression or paradoxical CNS stimulatory effects, anticholinergic activity or hypersensitivity reactions.

Anticholinergic effects: dry mouth, urinary retention, constipation or disturbance of accommodation are observed rarely and mainly in elderly patients. Drowsiness and general weakness may occur, especially at the beginning of treatment with the drug. If these effects do not disappear after a few days from the start of therapy, the dose of the drug must be reduced.

There have been reports of other side effects, such as headache, dizziness, increased sweating, hypotension, tachycardia, allergic reactions, nausea, fever, changes in liver function tests, bronchospasm. No clinically significant respiratory depression was observed when prescribed doses.

Involuntary motor activity, incl. very rare cases of tremors and convulsions, disorientation were observed with significant overdose.

Interaction

Atarax® potentiates the effect of drugs that depress the central nervous system, such as opioid analgesics, barbiturates, tranquilizers, hypnotics, ethanol (combinations require individual selection of drug doses).

Atarax®, when used simultaneously, interferes with the pressor effect of epinephrine (adrenaline) and the anticonvulsant activity of phenytoin, and also interferes with the action of betahistine and cholinesterase blockers.

With simultaneous use, Atarax® does not affect the activity of atropine, belladonna alkaloids, cardiac glycosides, antihypertensive drugs, histamine H2 receptor blockers.

Co-administration of Atarax with MAO inhibitors and anticholinergics should be avoided.

Hydroxyzine is an inhibitor of the CYP2D6 isoenzyme and, when used in high doses, may cause interactions with CYP2D6 substrates. Since hydroxyzine is metabolized in the liver, an increase in its concentration in the blood can be expected when co-administered with liver enzyme inhibitors.

How to take, course of administration and dosage

Inside.

Children: for the symptomatic treatment of itching. At the age of 12 months to 6 years - from 1 to 2.5 mg/kg/day of Atarax in several doses, from 6 years and older - from 1 to 2 mg/kg/day in several doses.

For premedication - 1 mg/kg 1 hour before surgery, and additionally the night before anesthesia.

Adults: For the symptomatic treatment of anxiety, 25–100 mg daily in divided doses throughout the day or at night. The standard dose of Atarax is 50 mg per day (12.5 mg in the morning, 12.5 mg in the afternoon and 25 mg at night).

In serious cases, the dose may be increased to 300 mg per day.

For premedication in surgical practice, 50–200 mg (1.5–2.5 mg/kg IM) is administered 1 hour before surgery.

For symptomatic treatment of itching, the initial dose is 25 mg; if necessary, the dose can be increased 4 times (25 mg 4 times a day).

In elderly patients, treatment begins with half the dose of Atarax. In case of renal and/or liver failure, doses should be reduced.

A single maximum dose should not exceed 200 mg, the maximum daily dose should not exceed 300 mg.

Overdose

A manifestation of an overdose of the drug Atarax may be a pronounced anticholinergic effect, depression or paradoxical stimulation of the central nervous system.

Symptoms (with significant overdose): nausea, vomiting, involuntary motor activity, hallucinations, impaired consciousness, arrhythmia, arterial hypotension.

Treatment: if there is no spontaneous vomiting, it is recommended to immediately lavage the stomach and induce vomiting artificially. General supportive measures are indicated, including monitoring the vital functions of the body and monitoring the patient until the symptoms of intoxication disappear and in the next 24 hours. If it is necessary to obtain a vasopressor effect, norepinephrine or metaraminol is prescribed. Epinephrine should not be prescribed. Hemodialysis is not effective. There is no specific antidote.

Special instructions

If allergy tests are necessary, Atarax should be discontinued 5 days before the test.

Since hydroxyzine can affect attention and the speed of psychomotor reactions, patients should be warned about this if it is necessary to drive a car or operate machinery.

Release form

Atarax tablets, white, oblong, film-coated, with a dividing transverse score on both sides.

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Best before date

5 years

Active substance

Hydroxyzine

Conditions for dispensing from pharmacies

On prescription

Dosage form

pills

Purpose

For children as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Mental disorders, Obsessive-compulsive disorder, Allergies, Alcoholism

Information in the State Register of Medicines

Barcode and weight

Barcode: 4603149000083, 5413787104512 Weight: 0.015 kg

Side effects

Side effects associated with anticholinergic effects: rarely (mainly in elderly patients) - dry mouth, urinary retention, constipation, impaired accommodation.

From the central nervous system: drowsiness, general weakness (especially at the beginning of treatment), headache, dizziness. If weakness and drowsiness do not disappear after a few days from the start of therapy, the dose of the drug must be reduced. Very rarely (with significant overdose) - tremors, convulsions, disorientation.

From the cardiovascular system: arterial hypotension, tachycardia.

From the digestive system: nausea, changes in liver function tests.

Other: increased sweating, allergic reactions, fever, bronchospasm.

When using the drug in recommended doses, no clinically significant respiratory depression was observed. Involuntary motor activity (including very rare cases of tremors and convulsions), disorientation were observed with significant overdose.

Side effects observed when taking Atarax are usually mild, transient and disappear within a few days of starting treatment or after reducing the dose.

Side effects

Since Atarax is a drug that acts on the central nervous system, it can sometimes cause suppression of certain functions or paradoxical stimulation. Also, when taking it, negative reactions from the body may occur:

From the cardiovascular system: blood pressure rarely decreases, heart rate increases.
From the point of view: decreased clarity of vision, impaired accommodation.
From the gastrointestinal tract: a feeling of dry mouth, rarely - vomiting, nausea, problems with intestinal motility and, as a result, constipation.
From the immune system: hypersensitivity, rarely anaphylactic shock may develop.
From the urinary system: urine retention is rarely possible.
From the respiratory system: rarely - bronchospasm and suffocation.
Neurological disorders: drowsiness, headache, insomnia, dizziness, rarely – convulsions.
Mental disturbances are rare: agitation, disorientation, and hallucinations are possible.
Skin: itching, rash, rarely - swelling.
General disorders: weakness, fever, fatigue.

Overdose

Symptoms: increased anticholinergic effects, depression or paradoxical stimulation of the central nervous system, nausea, vomiting, involuntary motor activity, hallucinations, impaired consciousness, arrhythmia, arterial hypotension; rarely - tremors, convulsions, disorientation, which occur with a significant overdose.

Treatment: if spontaneous vomiting is absent, it is necessary to induce it artificially or perform gastric lavage. Carry out general measures aimed at maintaining the vital functions of the body, and monitor the patient until the symptoms of intoxication disappear in the next 24 hours.

If it is necessary to obtain a vasopressor effect, norepinephrine or metaramenol is prescribed. Epinephrine should not be used. There is no specific antidote. The use of hemodialysis is ineffective.

Drug interactions

Atarax potentiates the effect of drugs that depress the central nervous system, such as opioid analgesics, barbiturates, tranquilizers, hypnotics, ethanol (combinations require individual selection of drug doses).

Atarax, when used simultaneously, interferes with the pressor effect of epinephrine (adrenaline) and the anticonvulsant activity of phenytoin, and also interferes with the action of betahistine and cholinesterase blockers.

With simultaneous use, Atarax does not affect the activity of atropine, belladonna alkaloids, cardiac glycosides, antihypertensive drugs, histamine H2 receptor blockers.

Co-administration of Atarax with MAO inhibitors and anticholinergics should be avoided.

Compatibility with other drugs

A separate issue when taking Atarax is its interaction with other medications. Thus, barbiturates, tranquilizers, opioid analgesics, ethanol-containing drugs, sleeping pills and any other drugs that depress the central nervous system, when taken simultaneously with the drug Atarax, enhance the effects. That is, lethargy, indifference, drowsiness and other effects will appear several times brighter and stronger. But if it is still necessary to take everything together, then the doctor monitoring the patient will draw up a dosage regimen and select an individual dosage for each drug.

Compatibility of other drugs with Atarax

The combination of Atarax + MAO inhibitors, anticholinergics is not recommended. Atarax is able to inhibit the action of epinephrine (adrenaline) and suspend the anticonvulsant effect of phenytoin.

Atarax has a destructive effect on the metabolism of substrate drugs for uridine diphosphate and glucuronyl transferase.

If you drink Cimetidine and Atarax at the same time, the concentration of hydroxyzine in the blood plasma will increase, but on the contrary, the concentration of metabolites will decrease.

As for cardiac glycosides, atropines, antihypertensive drugs, antiallergic drugs, Atarax does not in any way affect their functionality; the pharmacological effect provided.

However, it is worth remembering that it is better not to take drugs whose side effects indicate possible arrhythmia with Atarax. When they are mixed, there is a risk of prolongation of the QT interval and the development of ventricular tachycardia of the “pirouette” type.

special instructions

If allergy tests are necessary, Atarax should be discontinued 5 days before the test.

Patients taking Atarax should avoid drinking alcohol.

Impact on the ability to drive vehicles and operate machinery

Patients taking Atarax, if necessary to drive a car or operate machinery, should be warned that the drug may affect concentration and the speed of psychomotor reactions.