Doxylamine-SZ
Dosage form
film-coated tablets
Compound
1 tablet contains:
Dosage 15 mg:
active ingredient: doxylamine succinate – 15 mg;
excipients: microcrystalline cellulose – 15.0 mg, croscarmellose sodium – 9.0 mg, lactose monohydrate (milk sugar) – 98.2 mg, magnesium stearate – 1.4 mg, colloidal silicon dioxide (aerosil) – 1.4 mg ;
shell composition: hypromellose – 2.04 mg, polysorbate-80 (Tween-80) – 0.85 mg, talc – 0.68 mg, titanium dioxide E 171 – 0.43 mg.
Description
White film-coated tablets, round, biconvex, scored. On a cross-section, the core of the tablet is white or almost white.
ATX code
R06AA09
Pharmacological properties
Pharmacodynamics
Blocker of Hl-histamine receptors from the group of ethanolamines. It has a hypnotic, sedative and M-anticholinergic effect. Reduces the time to fall asleep, increases the duration and quality of sleep, without changing the sleep phases. Duration of action – 6-8 hours.
Pharmacokinetics
The maximum concentration in blood plasma (Cmax) is achieved on average 2 hours after oral administration. The half-life of doxylamine (T1/2) is about 10 hours.
Absorption is high, metabolized in the liver. Penetrates well through histohematic barriers, including the blood-brain barrier. 60% is excreted unchanged by the kidneys, partially through the gastrointestinal tract (GIT).
Pharmacokinetics of the drug in special groups of patients
In patients over 65 years of age, as well as with hepatic and renal insufficiency, the half-life may be prolonged. When repeated courses of treatment, a stable concentration of the drug and its metabolites in the blood plasma is achieved later and at a higher level.
Indications for use
Transient sleep disturbances.
Contraindications
– hypersensitivity to doxylamine and other components of the drug, or to other antihistamines;
– angle-closure glaucoma or family history of angle-closure glaucoma;
– diseases of the urethra and prostate gland, accompanied by impaired urine outflow;
– congenital galactosemia, glucose-galactose malabsorption, lactase deficiency;
– childhood and adolescence (up to 15 years).
Carefully
Patients with a history of apnea - due to the fact that doxylamine can aggravate sleep apnea syndrome (sudden cessation of breathing during sleep).
Patients over 65 years of age - due to possible dizziness and delayed reactions with the risk of falls (for example, when waking up at night after taking sleeping pills), as well as due to a possible increase in the half-life.
Patients with renal and hepatic insufficiency (half-life may increase).
Use during pregnancy and breastfeeding
Based on adequate and well-controlled studies, doxylamine can be used in pregnant women throughout pregnancy.
If this drug is prescribed in late pregnancy, the atropine-like and sedative properties of doxylamine should be taken into account when monitoring the condition of the newborn.
It is not known whether doxylamine passes into breast milk. Due to the possibility of developing a sedative and stimulating effect in a child, breastfeeding should not be done while using the drug.
Directions for use and doses
Inside. 1/2 - 1 tablet per day, with a small amount of liquid, 15-30 minutes before bedtime.
If treatment is ineffective, on the recommendation of a doctor, the dose can be increased to two tablets.
Duration of treatment from 2 to 5 days; If insomnia persists, you should consult a doctor.
Use in special groups of patients
Patients with renal
and
liver failure:
Due to data on increased plasma concentrations and decreased plasma clearance of doxylamine, a downward dose adjustment is recommended.
Use in patients over 65
years:
H1-histamine receptor blockers should be prescribed with caution to this group of patients due to possible dizziness and delayed reactions with the risk of falls (for example, during night awakenings after taking sleeping pills). In view of data on increased plasma concentrations, decreased plasma clearance and increased half-life, a downward dose adjustment is recommended.
Side effect
From the gastrointestinal tract:
constipation, dry mouth.
From the cardiovascular system:
feeling of heartbeat.
From the organ of vision: visual impairment and accommodation, blurred vision.
From the kidneys and urinary tract:
urinary retention.
From the nervous system: drowsiness during the day (in this case, the dose of the drug should be reduced), confusion, hallucinations.
From laboratory parameters: an increase in the level of creatine phosphokinase.
From the musculoskeletal system:
Rhabdomyolysis
If any of
the adverse reactions indicated in or you notice any other adverse effects not listed in the instructions, notify your doctor
.
Overdose
Symptoms: daytime drowsiness, agitation, pupil dilation (mydriasis), accommodation disturbances, dry mouth, redness of the skin of the face and neck (hyperemia), increased body temperature (hyperthermia), sinus tachycardia, disturbance of consciousness, hallucinations, decreased mood, anxiety, disturbance coordination of movements, trembling (tremor), involuntary movements (athetosis), convulsions (epileptic syndrome), coma. Involuntary movements are sometimes a precursor to seizures, which may indicate severe poisoning. Even in the absence of seizures, severe doxylamine poisoning can cause rhabdomyolysis, which is often accompanied by acute renal failure. In such cases, standard therapy with constant monitoring of creatine phosphokinase levels is indicated.
If symptoms of poisoning appear, consult a doctor immediately.
Treatment: symptomatic (m-cholinomimetics, etc.), activated carbon is indicated as a first aid remedy (50 g for adults and 1 g/kg body weight for children).
Interaction with other drugs
When taking the drug Doxylamine-SZ simultaneously with sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), barbiturates, benzodiazepines, clonidine, morphine derivatives (analgesics, antitussives), neuroleptics, anxiolytics, sedative H1 - antihistamines, central antihypertensives drugs , thalidomide, baclofen, pizotifen enhances the inhibitory effect on the central nervous system (CNS).
When taken simultaneously with m-anticholinergic drugs (atropine, imipramine antidepressants, antiparkinsonian drugs, atropine antispasmodics, disopyramide, phenothiazine antipsychotics), the risk of side effects such as urinary retention, constipation, and dry mouth increases.
Since alcohol enhances the sedative effect of most H1-histamine receptor antagonists, incl. and the drug Doxylamine-SZ, it is necessary to avoid its simultaneous use with alcoholic beverages and medications containing alcohol.
special instructions
It should be taken into account that insomnia can be caused by a number of reasons for which there is no need to prescribe this drug.
The drug Doxylamine-SZ has a sedative effect, suppresses cognitive abilities and slows down psychomotor reactions. The first generation of H1-antihistamines can have m-anticholinergic, anti-alpha-adrenergic and antiserotonin effects, which can cause dry mouth, constipation, urinary retention, disturbances of accommodation and vision.
Like all sleeping pills or sedatives, doxylamine may worsen sleep apnea (sudden stoppage of breathing during sleep), increasing the number and duration of apnea attacks.
One tablet of the drug contains 98.2 mg of lactose monohydrate, which should be taken into account in patients with rare congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Impact on the ability to drive vehicles and operate machinery
Due to possible drowsiness during the daytime, you should avoid driving vehicles, operating machinery and other activities that require increased concentration and speed of psychomotor reactions.
Release form
Film-coated tablets, 15 mg.
10 or 30 tablets per blister pack.
30 tablets in polymer jars made of low-density polyethylene with a tension-controlled lid made of high-density polyethylene or in polymer bottles made of low-density polyethylene with a tension-controlled lid made of high-density polyethylene.
Each jar, bottle, 1, 2, 3, 5 blister packs of 10 tablets or 1, 2 blister packs of 30 tablets, together with instructions for use, are placed in a cardboard box.
Best before date
3 years. Do not use after the expiration date stated on the package.
Storage conditions
In a place protected from light, at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Vacation conditions
Available with prescription
Prescription drug
Prescription drug
Use of the drug Donormil (doxylamine) in clinical practice
The main indications for prescribing Donormil are insomnia and sleep disorders. Contraindications for use: angle-closure glaucoma, difficulty urinating (diseases of the urethra and prostate), age under 15 years, lactation, hypersensitivity to the drug. Possible side effects are associated with the anticholinergic effect of the drug: dry mouth, impaired accommodation, constipation, urinary retention. It should be remembered that in the morning, after taking the drug in the evening, there may be a slower reaction and a feeling of dizziness, therefore, to prevent falling, sudden movements should be avoided. The drug is prescribed to adults and children over 15 years of age, 7.5–15 mg (½–1 tablet) per dose, 15 minutes before bedtime (in the evening). If necessary, the dose of Donormil can be increased to 30 mg per day. The film-coated tablet should be taken with water. The duration of treatment is from 2 to 5 days [6]. In case of an overdose of Donormil, which increases the side effects, agitation, mydriasis, paralysis of accommodation, flushing of the skin of the face and neck, hyperthermia, convulsions, and sinus tachycardia may appear. The phase of excitement and convulsions may be preceded by a state of depression. Such manifestations always require urgent therapy with the involvement of resuscitators. Modern clinical studies do not reveal serious side effects during treatment with therapeutic doses, but it is always necessary to remember the possible appearance of these symptoms that arise due to the individual characteristics of the body, and contraindications [10]. When Donormil is prescribed, daytime drowsiness may occur [1]. However, given the good safety profile of Donormial, it is recommended as a “first-line” drug in the treatment of chronic or newly diagnosed insomnia, unless the patient has obvious contraindications to the administration of this dosage form [3]. Currently, a disorder associated with difficulties in initiating and/or maintaining sleep, despite the presence of all the necessary conditions, is classified as insomnia [12]. Insomnia is a disorder associated with difficulty falling or staying asleep. According to DSM-IV, insomnia is defined as a deficiency in the quality and quantity of sleep necessary for normal daytime functioning. According to ICD-10, insomnia, hypersomnia and sleep rhythm disturbances are generally defined as “primarily psychogenic conditions with an emotionally caused disturbance in the quality, duration or rhythm of sleep” [5,15]. Use of Donormil in general somatic practice The prevalence of sleep disorders in the general somatic network is quite high. Thus, only severe insomnia, requiring drug correction, occurs in 14% of patients being treated in a hospital for any somatic disease [10]. Some surveys estimate that up to 20% of middle-aged people in the population require examination for sleep disorders [24]. Epidemiological studies on sleep disorders show that about 24% of people complain of sleep disorders – insomnia [18]. Sleep disorders can lead to temporary or long-term disability, and are often the cause of non-standard and emergency situations, which determines their medical and social significance [24]. The causes of insomnia are varied: stress, neuroses, mental neurological somatic diseases (including cardiovascular); psychotropic drugs, alcohol, toxic factors; endocrine-metabolic diseases, syndromes that occur during sleep (sleep apnea syndrome; motor disorders during sleep), pain phenomena, external unfavorable conditions (noise, humidity, etc.), shift work, jet lag, poor sleep hygiene. Most often, insomnia is associated with anxiety and depression and therefore can be considered a psychosomnic disorder [18]. A multicenter, randomized, double-blind, 3-parallel group study of 338 patients aged 18 to 73 years compared the efficacy and tolerability of Donormil (doxylamine) 15 mg with zolpidem 10 mg and placebo in the treatment of insomnia (including withdrawal studies). The high quality of sleep observed during therapy with the studied drugs persisted for 1 week after discontinuation of the drugs. Among the undesirable effects noted: drowsiness, asthenia, fatigue - in 13.5% of patients receiving Donormil (doxylamine), and in 6.7% of patients receiving zolpidem. Functional gastrointestinal disorders were more common with zolpidem (9.3%) than with placebo (7.3%) and Donormil (doxylamine) (7.2%). These manifestations resolved independently upon cessation of course therapy. The overall assessment of drug tolerability after 2 weeks of therapy was positive in 85% of cases. The study confirmed the advantage of Donormil over placebo in terms of hypnotic effects, which demonstrated high efficiency and good tolerability of the studied drugs without the development of “withdrawal syndrome” [4]. The most common breathing disorder during sleep is obstructive sleep apnea, a potentially life-threatening sleep apnea. Since sleep apnea is often combined with a decrease in air flow through the upper respiratory tract (hypopnea), it is customary to combine both of these conditions into a pathological syndrome complex - “obstructive sleep apnea-hypopnea syndrome” (OSAS). Respiratory disorders during sleep are accompanied by episodes of a pronounced decrease in arterial blood oxygen saturation (blood desaturation) and the development of hypoxia of the heart, brain, and kidneys. Hypoxia of these vital organs is usually accompanied by sudden changes in blood pressure and heart rhythm disturbances, which can lead to sudden death during sleep. The prevalence of obstructive sleep apnea syndrome among men aged 30–60 years is 4%, among women – 2%. The most important factors that influence the likelihood of developing OSA are body weight, gender, age, condition of the facial skeleton and the presence of ENT pathology [21]. The treatment program for patients with OSAHS includes basic (CPAP machine, dental (oral) applicators) and conservative (weight loss, side sleeping, abstinence from alcohol for 2 or 3 hours before bedtime, abstinence from certain pharmacological agents, smoking cessation) treatment tactics that are aimed at maintaining the constancy of the airway lumen during sleep. In case of even minimal suspicion of the presence of OSAHS as a cause of insomnia and the impossibility of polysomnographic verification, it is better to use Donormil as a sleeping pill, the duration of which should not exceed 3 weeks (optimally 10–14 days). [3,5,9,11]. Each person needs a different amount of sleep; the average nightly sleep requirement for an adult is 7–8 hours, although variations from this norm are quite wide. Some people feel great after 5-6 hours of sleep, while others need 9-10 hours. With age, the number of people with short sleep duration (less than 6 hours) increases: 18–25 years old – 12%, 26–35 years old – 20.8%, 46–60 years old – 61% [8]. The clinical phenomenology of insomnia includes presomnic, intrasomnic and postsomnic disorders. An objective study of patients with insomnia necessarily includes polysomnography. This technique involves the simultaneous recording of several parameters, such as electroencephalography, electromyography, electrooculography, which is the minimum required set for assessing sleep structure [12–15]. More than 20% of middle-aged patients and 36% of elderly patients complain of all three types of sleep disorders, and these groups are usually the most difficult to manage. Patients often complain of a complete lack of sleep for many nights, but with an objective polysomnographic study, sleep is not only present, but its duration exceeds 5 hours (sometimes reaching 8 hours), and the structure of sleep is not too deformed. This situation is defined as sleep agnosia. The cause of its occurrence has not been determined, but more often a similar phenomenon is observed in women aged 46 to 60 years who do not have severe emotional and somatic disorders, and in patients suffering from mental illnesses [7]. To clinically assess the severity of insomnia, a 5-point sleep scale questionnaire is used, which includes the following indicators: time of falling asleep, duration of sleep, number of night awakenings, quality of sleep, number of dreams, quality of morning awakening. A score below 19 points is a sign of trouble [16]. Prescription of Donormil in cardiac patients Any sleep disorders have a negative impact on human health, since sleep is the most important regulator of the body's circadian (circadian) biological rhythms. Cardiovascular pathology itself creates conditions for disruption of human circadian rhythms. The existing circadian changes are also accompanied by sleep disturbances, which accompany and aggravate the course of cardiovascular diseases [1,2]. These disturbances in the biological rhythms of hormonal levels and hemodynamics indicate a state of tension in the cardiovascular system precisely in the evening and night hours. Sadovnikova I.I. statistical data are presented: the maximum frequency of development of hypertensive crises occurs in the period of 16–24 hours, especially from 19 to 23 hours; acute left ventricular failure – 21–23 hours; myocardial infarction – in the period of 1–2 hours, two peaks – morning (8–10 o’clock) and evening (17–18 o’clock); recurrence of myocardial infarction – 0–3 hours, 15–16 hours, 19–21 hours; pulmonary edema – from 19:00 to 3:00; paroxysmal tachyarrhythmia – 15–19 hours; ventricular fibrillation – 4–10 hours, 17–20 hours. The existing circadian changes (mainly at night) in these patients are accompanied by sleep disturbance and depressive syndrome, which necessarily accompanies IHD and hypertension. This implies the need and expediency of assessing the patient’s complaints about changes in sleep and mandatory correction of these deviations [22]. In patients with cardiovascular pathology, as a rule, two types of sleep disorders are distinguished: disorders with predominantly early awakenings and disorders with frequent awakenings at night. In the study of Adamenko R.Ya. (2005) included 62 patients (20 men and 42 women aged 46–78 years) whose sleep disturbances were associated with arterial hypertension (AH). All patients presented pre-, intra- or post-somnic complaints to one degree or another. For the treatment of sleep disorders, all patients were prescribed Donormil at a dose of 7.5–15 mg nightly, 15 minutes before bedtime. In all patients, as a result of treatment, the time to fall asleep was significantly reduced (to normal values), normal sleep duration occurred, presomnia disorders disappeared, night awakenings were observed less frequently, and the level of wakefulness after sleep improved [11]. 20% of myocardial infarctions and 15% of cases of sudden death occur during night sleep, while myocardial infarctions that develop at night have a more severe course and poor prognosis. Angina attacks also often occur in the evening and at night and cause insomnia. The emotional stress of patients with angina pectoris increases due to the fear of another attack and death in their sleep. In patients suffering from coronary artery disease, night apnea can provoke rhythm disturbances in the form of ventricular tachycardia; in some cases, the development of atrioventricular block of II–III degree is possible. One of the reasons for the low effectiveness of antihypertensive therapy is sleep disturbance, which, according to the literature, is observed in approximately 42% of patients with hypertension. Sleep disturbance leads to an increase in average daily blood pressure due to an increase in night pressure. In such patients, the period of wakefulness is extended with higher blood pressure numbers and an increase in blood pressure the next day, and the degree of nighttime decrease in blood pressure decreases. All this leads to the appearance of a pathological type of daily blood pressure curve. In order to correct sleep disorders in cardiac patients, benzodiazepine drugs are traditionally used, although they do not always meet the requirements of effectiveness and safety. Often, while taking these drugs, there is an excessive sedative effect, which is difficult for cardiac patients suffering from asthenia. It is also possible that cognitive deficits may increase, which contributes to social maladjustment. Some benzodiazepines can cause vascular hypotension in the elderly and in patients with impaired vascular tone. In patients with coronary heart disease, reflex tachycardia may develop. In cardiological practice, Donormil is prescribed in a dose of 15 mg, ½–1 tablet per 30 minutes. before sleep. [2]. Prescribing Donormil to neurological patients Data from studies conducted in a number of clinics in Ukraine indicate that sleep disorders are present in 86.5% of patients hospitalized in neurological departments [8]. Currently, in the arsenal of doctors, primarily somnologists and neurologists, for the drug treatment of sleep disorders there are three generations of sleeping pills: 1st generation - barbiturates, antihistamines, chloral hydrate, propanediol, paraldehyde; 2nd generation – benzodiazepine derivatives – nitrazepam, diazepam, etc.; 3rd generation – cyclopyrrolone derivatives (zopiclone) and imidazopyridine derivatives (zolpidem). The limitation in the use of these drugs is their side effects (they can disrupt daytime wakefulness and also cause drug dependence). But even now, drugs of this group are actively used to treat insomnia, especially in combination with anxiety disorders. Along with the synthesis of drugs aimed strictly at the treatment of sleep disorders, drugs from other pharmacological groups are constantly being studied, the effects of which include sleeping pills. Such drugs include Donormil (doxylamine succinate) [10]. Unlike benzodiazepine derivatives, Donormil not only increases the duration and improves the quality of sleep, but also does not disrupt the physiological phases of normal sleep and circadian rhythms. Perhaps this is the only sleeping pill that has no contraindications regarding the possibility of developing sleep apnea [11]. On the territory of the Russian Federation, an open non-comparative study of the drug Donormil was conducted in 50 patients with insomnia aged from 24 to 60 years, undergoing outpatient and inpatient treatment in sleep centers and a neurological department (10 patients were examined using polysomnography). All patients took Donormil 15 mg 15 minutes before bedtime for 10 days. As a result of the study of the effect of Donormil on patients with insomnia, a positive dynamics of subjective sleep characteristics was obtained (14.4 points “before” vs. 19.7 points “after”), the results of the “sleep apnea” screening questionnaire (3.0 points “ before" vs 2.9 b. "after"). Subjective feelings of a positive effect are confirmed by studies of sleep structure undergoing positive changes, which affect such indicators as sleep duration (305.3 minutes “before” vs 341.6 minutes “after”), duration of falling asleep (49.3 minutes “before” vs 21.1 minutes “after”), REM sleep phase (43.1 minutes “before” vs 56.7 minutes “after”). It has been shown that Donormil has a greater effect on patients with more severe sleep disorganization. It was concluded that, given its high effectiveness and safety, Donormil can be recommended to a wide range of patients with sleep disorders, both acute and chronic insomnia [14]. When taking Donormil as a sleeping pill, the natural structure of sleep is preserved, there is no addiction or dependence (withdrawal syndrome does not develop), the use of the drug is not accompanied by deterioration of cognitive functions. In a study conducted at the Moscow City Somnology Center and the Department of Nervous Diseases of the First Moscow State Medical University named after I.M. Sechenov demonstrated the effectiveness of Donormil in relation to both subjective (according to questionnaires) and objective (according to polysomnography) sleep indicators in patients with insomnia. When comparing the data of these patients before and after treatment, an improvement in the total score of sleep quality was revealed by 37%, there was a significant (at p<0.05) increase in sleep duration, delta sleep latency time and the amount of REM sleep, a decrease in the time of falling asleep and sleep quality index. There was no negative effect of the drug on breathing parameters during sleep [19,20]. A study was conducted to evaluate the effectiveness of the use of antidepressants (using the example of paroxetine from the group of serotonin reuptake inhibitors) in combination with Donormil in the treatment of sleep disorders in patients with post-stroke depression [16]. The study included 49 patients (24 women and 25 men) who had suffered a stroke (2-3 weeks ago), aged from 47 to 64 years. The average score on the CES - D depression scale was 26.4 ± 1.9, which corresponds to a mild and moderate degree of depression. In all studied patients with depression, pronounced sleep disorders were noted - the sum of the points on the subject of the subjective characteristics of sleep was 16.1 ± 0.6. Patients were divided into two groups: the main (n = 27) - receiving 20 mg of paroxetine in combination with 15 mg of donormil at night, and the control - received only paroxetine. The dynamics of the state was estimated after 14 and 21 days. The study showed that the integrated use of paroxetine and donation contributed to a reliable improvement of sleep indicators in patients with the main group by 30% with a simultaneous reduction in the severity of depressive disorders by 26.1% by the end of the 2nd week of treatment. In the control group for this temporary interval, reliable changes in the indicators under study were not noted. A second study after 3 weeks showed: in the main group, the total score on the scale of the subjective characteristics of sleep was 26.6 ± 0.5, the average score along the CES - D depression scale against the background of depression reduction - 16.2 ± 1.7; In the control group, the improvement of sleep indicators to 21.0 ± 0.7 points, a decrease in depression indicators to 17.1 ± 1.6 points. Thus, the treatment of sleep disturbances in patients with post -industry depression is advisable to carry out a combination of antidepressant from the group of reverse capture of serotonin and donormil. In a study of chronic cerebrovascular diseases, a high frequency of Inssonia was revealed: 85% of patients with discirculatory encephalopathy of 426 examined expressed complaints about the quality and duration of night sleep. A study was conducted on the study of the tolerance and effectiveness of donormil (doxilamin) for insessonia in patients with discirculatory encephalopathy, in which the quality and quantitative indicators of sleep before and after treatment with donormil were carried out [23]. The study included 30 patients (22 women and 8 men) with a diagnosis of discirculatory atherosclerotic encephalopathy I and II, aged 55 to 68 years. In the group of patients, complaints about sleep disorders, increased fatigue, headaches, decreased memory and attention, instability of gait, impairment of hearing and vision prevailed. The frequency of manifestation of insomnic disorders is from 3 to 7 times a week, duration of 2 months. up to 3 years. To objectify sleep disturbances, a questionnaire was used. Presomnical disorders were noted in 20%, post -soot in - 16.7% and intracnial - in 63.3% of cases. The instrumental study included electroencephalography, rheoencephalography and computed X -ray tomography of the brain. Patients under the age of 60 (73.3%) were prescribed at a dose of 15 mg (1 tablet), older than 60 years (26.7%) - 7.5 mg (1/2 tablets) 15 minutes before going to bed within 10 days. During the study, a reliable improvement in the quality of sleep quality was obtained: the time of falling asleep decreased, the number of anxious dreams and night awakenings decreased, the lack of drowsiness and general weakness in the morning was noted. The total duration of sleep after treatment has approached physiological indicators - this corresponds to an increase in the total score of 49.6%. There were no undesirable phenomena during the administration of the donor. Thus, the results indicate the high effectiveness of donation in sleep disorders, its good tolerance and the possibility of recommending the drug for correction of chronic imbalance in patients with discirculatory encephalopathy [23]. Fibromyalgia, one of the causes of sleep disturbance is a diffuse, symmetrical non -devastating pain, which is chronic and accompanied by stiffness, depression, sleep disturbances and the presence of characteristic pain points. Sleep disturbances in fibromyalgia are almost a bodge of it [25]. The representation of fibromyalgia is about 4% in the population, 6-10% in general clinical practice and over 15% in rheumatological. Active complaints of patients about the difficulties of falling asleep, frequent awakening in the middle of the night and superficial sleep are observed in 74.6% of patients. At the same time, the most serious complaints about the absence of a feeling of rest after a night sleep, which served as the basis for denoting a dream in fibromyalgia, as an “non -contingal” - this phenomenon is noted in 96% of cases. The polysonographic pattern of sleep in patients with fibromyalgia is characterized by an increase in the representation of the surface stages of sleep, the time of wakefulness inside the night, movements in the dream, reduction of the phase of quick sleep [25]. The aggravating factor in sleep disturbance in patients with fibromyalgia is depressive disorders. In approximately 64% of cases, depressive episodes precede the appearance of the main symptoms of the disease, 71% in the history of the previously depressive disorders, when analyzing which certain polysographic features were shown depending on the level of depression, namely, with an increase in the level of depression, the time of wakefulness increases In a dream, the activation index of movements of the 1st stage, the number of "carotid" spindles is reduced [25]. A special randomized double -related placebo -controlled study of the effect of donormil (doxylamine) on the structure of sleep and the state of cognitive functions, memory and reaction rate with a single administration of 15 mg of donormil (doxilaminat) or placebo in healthy volunteers was carried out. The indicators of the total duration of sleep, the number of awakenings during sleep, the number of sleep cycles in the group of doxilamin and placebo did not differ. After taking a donor (doxilamin), the total duration of awakening during sleep was significantly reduced. Reception of a donormil (doxilamin) leads to a significant shortening of the first stage and lengthening the second stage. At the same time, donormil (doxylamine) does not affect the duration of the third and fourth stages and phases of quick sleep [15]. The appointment of a donormil in psychiatric practice conducted an open study on assessing the effectiveness of a donormil in a psychiatric clinic and determining the contingent of rector patients with borderline conditions and low -processing endogenous diseases [24]. The study was attended by 61 patients (28 men, 33 women, the average age - 42.16 ± 14.5 years), who was treated stationary or outpatiently in the clinic of the department for the study of border mental pathology and psychosomatic disorders of the NCPZ RAMS. Patients turned regarding anxious -phobic, depressive, astheno -apatical and hypochondriacal disorders, within the framework of which complaints of sleep disturbances were noted. The dynamics of the condition of patients was evaluated in the background and on the 15th day of therapy using psychopathological and psychometric (assessment of the subjective characteristics of sleep) examination methods. The donor was prescribed in doses from 7.5 to 30 mg in tablet or soluble form in 30 minutes. before going to bed (course - 15 calendar days). If there was no effect within 5 days, the course of treatment was stopped. The donor was prescribed in combination with other psychotropic drugs, but not simultaneously with tranquilizers, the evening intake of other drugs was moved to 18.00. At 50.8%, spontaneous sleep disturbances were identified, in 18% - situationally determined. The study was completely completed 68.8% of patients. In the analysis of psychopathological manifestations that determine the symptoms of Inssonia in this part of observations, it was revealed that in 53.1% of cases there is depressive, 4.3% anxious -phobic syndrome; There have also been cases of reduction of symptoms of insomnia, which developed within the framework of hypochondriacal (17.6%) and astheno -apatic (25%) disorders, respectively. In the course of the study, reliable changes in indicators were obtained to reduce the period of falling asleep - 73.8%, improving the quality of sleep (increase in depth and a decrease in the number of dreams), improving the quality of morning awakening (vigor, lack of drowsiness and breakdown, desire to lie in bed). It is noted that the drug practically does not affect the amount of night awakening. Unwanted phenomena are registered in 21.4% of the total number of responders in the form of a short -term (no more than 30 minutes) morning lethargy and drowsiness, and outpatient patients additionally reported the difficulties of including in labor activities that are reduced during the first 5 days of taking the drug independently or independently or With a decrease in the dose to 7.5 mg. Thus, donormil is effective for sleep disturbances in medium and mild severity that arose as an element of depressive, anxious -phobic, asthenapathic and hypochondriacal syndromes, or sleep disturbances forming as part of personality disorders, affective pathology of the cyclotic level or inaccidently -like (psychopathic) schizophrenia. Treatment of sleep disorders with a donormil is not accompanied by the effect of the Beginning. Given the data on the high efficiency and safety of the drug Donormil can be recommended to a wide range of patients with sleep disorders, which are formed during the pathology of the circle of "small" psychiatry. The use of donormil in obstetric and gynecological practice from 50 to 90% [17], according to other sources, 70–85% [26], all pregnant women suffer from nausea and vomiting (morning malaise of pregnant women). The effectiveness of doxilamin, which is prescribed for the treatment of nausea and vomiting in pregnant women, compared to placebo, has been proven. Numerous studies have not revealed the teratogenic effect of the drug on the fetus. It is effective to prescribe a doxilam 25 mg at night independently or in combination with pyridoxine 25 mg three times a day [17]. A randomized, double -blind, multicenter placebo -controlled study of the effectiveness of the effectiveness of the drug diclectin in pregnant women with complaints of nausea and vomiting was carried out [27]. The study included women (n = 131) who took diclectin (doxylamine succinate + pyrodoxin hydrochloride), and a group of women (n = 125) taking placebo. All symptoms were evaluated in points on special scales. The duration of the observation was 14 days. In the course of the study, it was shown that the prescription of diklectin to a greater extent of severity reduces the symptoms of nausea and vomiting in comparison with placebo (–4.8 ± 2.7 vs –3.9 ± 2.6) and increases the quality of life of patients. After the test was completed, 48.9% of women taking diclectin expressed the desire to continue taking the drug compared to 32.8% of women from the placebo group. Thus, the form of the release of the drug Diklectin, which contains doxils and pyridoxine, is the most effective nausea and vomiting in pregnant women [27]. Another randomized study was carried out on the assessment of effectiveness by different methods of nausea and /or vomiting at the early stages of pregnancy [26]. 21 women with a mild severity of nausea and vomiting of pregnant women were selected in the study. Such methods of treating nausea in pregnant women as antihistamines, pyridoxine, acupressure and ginger root extract were used. The reduction of the frequency of manifestation of symptoms of nausea in the prescription of anti -excavation agents has been noted. The effectiveness of all the means used is shown. During the study of teratogenic effects on the fetus from the use of each of the funds, no means were noted. Thus, we can conclude on the safety of the appointment of Debenddox, which includes a pre -oxylamin of a succinate, in the treatment of nausea in the early stages of pregnancy. 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