Dexamethasone tablets 0.5mg, No. 10

• Adrenal insufficiency

• thyroiditis,

• hypothyroidism,

• progressive ophthalmopathy,

• hemoblastosis,

• bronchial asthma,

• allergic diseases,

• rheumatism,

• rheumatoid arthritis,

• systemic connective tissue diseases,

• autoimmune hemolytic anemia,

• aplastic anemia,

• thrombocytopenia,

• agranulocytosis.

Inside, during or after meals (preferably in the early morning hours), the daily dose is 2-3 mg, in severe cases, up to 6 mg. After the onset of the therapeutic effect, the dose is gradually reduced to 0.5Ц1 mg / day.

For 1 tablet

Active substance:

Dexamethasone 0.50 mg

Excipients: lactose monohydrate, pregelatinized starch, colloidal silicon dioxide, magnesium stearate

• Arterial hypertension,

• Itsenko-Cushing's disease,

• psychosis,

• renal failure

• osteoporosis,

• peptic ulcer of the stomach and duodenum,

• bacterial endocarditis,

• syphilis,

• tuberculosis,

• diabetes,

• pregnancy.

Pharmacodynamics

Dexamethasone is a synthetic glucocorticosteroid (GCS), a methylated derivative of fluoroprednisolone, inhibits the release of interleukin-1 and interleukin-2, interferon gamma from lymphocytes and macrophages. It has anti-inflammatory, anti-allergic, desensitizing, anti-shock, anti-toxic and immunosuppressive effects. Suppresses the release of adrenocorticotropic hormone (ACTH) and beta-lipotropin by the pituitary gland, but does not reduce the content of circulating beta-endorphin. Inhibits the secretion of thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH).

Increases the excitability of the central nervous system (CNS), reduces the number of lymphocytes and eosinophils, increases the number of red blood cells (stimulates the production of erythropoietins).

Interacts with specific cytoplasmic receptors, forms a complex that penetrates the cell nucleus, stimulates the synthesis of matrix ribonucleic acid (mRNA), which induces the formation of proteins, including lipocortin, which mediate cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid and inhibits the synthesis of endoperoxides, prostaglandins (Pg), leukotrienes, which promote inflammation, allergies, etc.

Effect on protein metabolism: reduces the amount of protein in the plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumin in the liver and kidneys, and enhances protein catabolism in muscle tissue.

Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides (TG), redistributes fat (fat accumulation mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Effect on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract (GIT), increases the activity of glucose-6-phosphatase, leading to an increase in the flow of glucose from the liver into the blood, increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, leading to the activation of gluconeogenesis.

Influence on water-electrolyte metabolism: detains sodium ions (Na +) and water in the body, stimulates the excretion of potassium ions (K +) (mineralocorticosteroid (MCS) activity), reduces the absorption of calcium ions (Ca2 +) from the gastrointestinal tract, УflushesФ Ca2 + from bones, increases the excretion of Ca2 + by the kidneys.

The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils, induction of the formation of lipocortin and a decrease in the number of mast cells that produce hyaluronic acid, with a decrease in capillary permeability, stabilization of cell membranes and organelle membranes (especially lysosomal membranes).

Antiallergic effect develops as a result of suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in the number of T- and B-lymphocytes, mast cells , decrease in the sensitivity of effector cells to allergy mediators, inhibition of antibody production, changes in the body's immune response.

In chronic obstructive pulmonary disease (COPD), the action is mainly based on inhibition of inflammatory processes, inhibition of the development or prevention of edema of the mucous membranes, inhibition of eosinophilic infiltration of the submucous layer of the bronchial epithelium, deposition of circulating immune complexes in the mucous membrane of the bronchi, as well as inhibition of erosion and desquamation. ... Increases the sensitivity of small and medium-sized bronchial beta-adrenergic receptors to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of bronchial secretions by inhibiting or reducing its production.

The anti-shock and antitoxic effect is associated with an increase in blood pressure (BP) (due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenergic receptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane-protective properties, activation of liver enzymes involved in the metabolism of endo- and xenobiotics ... The immunosuppressive effect is due to inhibition of the release of cytokines (interleukin-1, interleukin-2, interferon gamma) from lymphocytes and macrophages. Suppresses the synthesis and secretion of ACTH, and secondarily - the synthesis of endogenous GCS. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

A feature of the action is a significant inhibition of the function of the pituitary gland and an almost complete absence of ISS activity. Doses of 1-1.5 mg / day inhibit the adrenal cortex, the biological half-life (T1 / 2) is 32-72 hours (the duration of the inhibition of the hypothalamus-pituitary-adrenal cortex).

In terms of the strength of glucocorticosteroid activity, 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone, or 17.5 mg of cortisone.

Pharmokinetics

Suction

After oral administration, it is rapidly and completely absorbed, the maximum concentration of dexamethasone in the blood plasma is 1-2 hours.

Distribution

In blood plasma, it binds (60-70%) with a specific carrier protein - transcortin. Easily passes through the histohematological barriers (including the blood-brain and placental barriers).

Metabolism

It is metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.

Withdrawal

It is excreted by the kidneys (a small amount of dexamethasone passes into breast milk). The half-life is 3-5 hours.

Overdose

Increase in dose-dependent side effects is possible, with the exception of allergic reactions. Dexamethasone dose should be reduced.

Treatment: symptomatic.

Side effects

The frequency of development and the severity of side effects depend on the duration of use, the size of the dose used and the possibility of observing the circadian rhythm of the appointment. Dexamethasone is generally well tolerated. It has a low ISS activity, that is, its effect on water-electrolyte metabolism is small. As a rule, low and medium doses of dexamethasone do not cause retention of Na + and water in the body, increased excretion of K +. The following side effects have been described:

Infectious and parasitic diseases: the development or exacerbation of infections (the appearance of this side effect is facilitated by the simultaneous use of immunosuppressants and vaccination), masking of infections.

Disturbances from the blood and lymphatic system: moderate leukocytosis, leukocyturia, lymphopenia, eosinopenia, polycythemia.

Immune system disorders: generalized (skin rash, pruritus, anaphylactic shock), local allergic reactions.

Disorders from the endocrine system: decreased glucose tolerance, 'steroid' diabetes mellitus or manifestation of latent diabetes mellitus, inhibition of adrenal function, Itsenko-Cushing's syndrome (moon face, pituitary obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myorrhea, myorrhea ), delayed sexual development in children.

Metabolic and nutritional disorders: hypercholesterolemia, increased Ca2 + excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, epidural lipomatosis.

Due to ISS activity - fluid and Na + retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

Mental disorders: nervousness or anxiety, insomnia, emotional lability, delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, suicidal tendencies.

Nervous system disorders: increased intracranial pressure, pseudotumor of the cerebellum, headache, convulsions.

Disturbances from the organ of vision: blurred vision, posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes in the cornea, exophthalmos, corneal perforation, central serous chorioretinopathy.

Hearing disorders and labyrinthine disorders: dizziness, vertigo.

Disturbances from the heart and blood vessels: arrhythmias, bradycardia (up to cardiac arrest), development (in predisposed patients) or progression of CHF, electrocardiographic changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis and thromboembolism, vasculitis, increased capillary fragility. In patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing down the formation of scar tissue, which can lead to rupture of the heart muscle.

Disorders from the digestive system: nausea, vomiting, abdominal pain, discomfort in the epigastric region, pancreatitis, 'steroid' ulcers of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the stomach and intestines, increased or decreased appetite, flatulence , hiccups. In rare cases - an increase in the activity of 'hepatic' transaminases and alkaline phosphatase.

Musculoskeletal and connective tissue disorders: growth retardation and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the humerus and femur head), muscle tendon rupture, 'steroid' myopathy, decreased muscle mass (atrophy).

Disorders from the skin and subcutaneous tissues: delayed wound healing, petechiae, ecchymosis, thinning of the skin, atrophy of the skin and subcutaneous tissue, hyper- or hypopigmentation, УsteroidФ acne, striae, a tendency to develop pyoderma and candidiasis, impaired skin pigmentation (hypo- or hyperpigmentation), telangiectasia.

General disorders and disorders at the injection site: withdrawal syndrome.

Special conditions

Prescribing dexamethasone for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously carry out specific antibiotic therapy when using the drug in patients with latent tuberculosis, lymphadenitis after vaccination with BCG, poliomyelitis, with acute and chronic bacterial, parasitic infections; with specific therapy in patients with gastric ulcer and / or intestinal ulcer, osteoporosis.

With daily use for 5 months of treatment, atrophy of the adrenal cortex develops.

May mask some symptoms of infections; it is useless to carry out immunization during treatment.

With the sudden cancellation of GCS, especially in the case of the previous use of high doses, there is a syndrome of УcancellationФ of GCS (not due to hypocorticism): decreased appetite, nausea, lethargy, generalized musculoskeletal pain, asthenia, and may also develop acute adrenal insufficiency (decrease BP, arrhythmia, increased sweating, weakness, oligoanuria, vomiting, abdominal pain, diarrhea, hallucinations, fainting, coma).

After withdrawal for several months, the relative insufficiency of the adrenal cortex persists. If during this period stressful situations arise, they are prescribed (according to indications) for the time of corticosteroids, if necessary in combination with mineralocorticosteroids.

The dose of dexamethasone must be temporarily increased in stressful situations during therapy (surgery, trauma). A temporary increase in the dose of the drug in stressful situations is necessary both before and after stress.

In children, during long-term treatment, careful monitoring of the dynamics of growth and development is necessary. Children who, during the period of treatment, were in contact with patients with measles or chickenpox, are prophylactically prescribed specific immunoglobulins.

During treatment with dexamethasone (especially long-term), it is necessary to observe an ophthalmologist, control blood pressure and water-electrolyte balance, as well as a picture of peripheral blood and blood glucose concentration. In order to reduce side effects, you can prescribe anabolic steroids, antacids, and also increase the intake of K + into the body (eating food rich in potassium and calcium, or taking potassium, calcium, and vitamin D preparations). Food should be rich in proteins, vitamins, low in fat, carbohydrates and salt.

In children during the period of growth, GCS should be used only for absolute indications and under the particularly careful supervision of the attending physician.

When using dexamethasone, there is a risk of developing severe anaphylactic reactions, bradycardia.

Against the background of drug therapy, the risk of strongyloidosis activation increases.

During therapy with the drug, careful monitoring of the condition of patients with CHF, uncontrolled arterial hypertension, trauma and ulcerative lesions of the cornea, glaucoma is necessary.

A worsening of the course of myasthenia gravis is possible.

Against the background of the use of corticosteroids, a change in sperm motility is possible.

Taking the drug can mask the symptoms of 'irritation of the peritoneum' in patients with perforation of the stomach or intestinal wall.

The effect of the drug is enhanced in patients with liver cirrhosis. It should be borne in mind that in patients with hypothyroidism, the clearance of dexamethasone decreases, and in patients with thyrotoxicosis, it increases.

In patients with diabetes mellitus, the concentration of glucose in the blood should be monitored and, if necessary, the doses of hypoglycemic drugs should be adjusted.

The appearance of visual impairment with systemic and local use of GCS is possible. If blurred or other visual impairment occurs, you should consider consulting an ophthalmologist to rule out causes such as cataracts, glaucoma, or rare eye diseases, such as central serous chorioretinopathy, which have been reported after systemic and topical administration of GCS.

Post-marketing surveillance has reported tumor lysis syndrome (TLS) in patients with hematological malignancies after using dexamethasone alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS (patients with high proliferative activity of tumor cells, high tumor load and high sensitivity to cytotoxic agents) require careful monitoring and adherence to appropriate precautions.

Premature babies

Available data indicate long-term neurological adverse events after initiation of therapy (<96 hours) with starting doses of 0.25 mg / kg dexamethasone twice daily in premature infants with chronic lung disease.

Specific information on excipients

The drug Dexamethasone - KRKA contains lactose, so it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Influence on the ability to drive vehicles, mechanisms

Taking into account the possible side effects during the period of therapy with the drug Dexamethasone - KRKA, care must be taken when driving vehicles and working with mechanisms, engaging in other activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

Dexamethasone increases the toxicity of cardiac glycosides (due to the resulting hypokalemia, the risk of arrhythmias increases).

”скор¤ет выведение ацетилсалициловой кислоты, снижает ее концентрацию в крови (при отмене дексаметазона концентраци¤ салицилатов в крови увеличиваетс¤ и возрастает риск развити¤ побочных ¤влений).

ѕри одновременном применении с живыми противовирусными вакцинами и на фоне других видов иммунизации увеличивает риск активации вирусов и развити¤ инфекций.

”величивает метаболизм изониазида, мексилетина (особенно у Ђбыстрых ацетил¤торовї), что приводит к снижению их плазменных концентраций.

”величивает риск развити¤ гепатотоксического действи¤ парацетамола (индукци¤ Ђпеченочныхї ферментов и образование токсичного метаболита парацетамола).

ѕовышает (при длительной терапии) содержание фолиевой кислоты.

vипокалиеми¤, вызываема¤ v —, может увеличивать выраженность и длительность мышечной блокады на фоне миорелаксантов.

¬ высоких дозах снижает эффект соматропина.

јнтациды снижают всасывание v —.

?ексаметазон снижает действие гипогликемических лекарственных средств, усиливает антикоагул¤нтное действие производных кумарина.

ќслабл¤ет вли¤ние витамина D на всасывание Ca2+ в просвете кишечника. Ёргокальциферол и паратгормон преп¤тствуют развитию остеопатии, вызываемой v —. ”меньшает концентрацию празиквантела в крови.

?иклоспорин (угнетает метаболизм) и кетоконазол (снижает клиренс) увеличивают токсичность.

“иазидные диуретики, ингибиторы карбоангидразы, другие v — и амфотерицин ¬ повышают риск развити¤ гипокалиемии, натрийсодержащие лекарственные средства - отеков и повышени¤ ј?.

Ќестероидные противовоспалительные препараты (Ќѕ¬ѕ) и этанол повышают опасность развити¤ изъ¤звлени¤ слизистой оболочки ? “, кровотечени¤, в комбинации с Ќѕ¬ѕ дл¤ лечени¤ артрита возможно снижение дозы v — из-за суммации терапевтического эффекта.

»ндометацин, вытесн¤¤ дексаметазон из св¤зи с альбуминами, увеличивает риск развити¤ его побочных эффектов.

јмфотерицин ¬ и ингибиторы карбоангидразы увеличивают риск развити¤ остеопороза. “ерапевтическое действие v — снижаетс¤ под вли¤нием фенитоина, барбитуратов, эфедрина, теофиллина, рифампицина и других индукторов Ђпеченочныхї микросомальных ферментов (увеличение скорости метаболизма).

ћитотан и другие ингибиторы функции коры надпочечников могут обусловливать необходимость повышени¤ дозы v —.

 лиренс v — повышаетс¤ на фоне гормонов щитовидной железы.

»ммунодепрессанты повышают риск развити¤ инфекций и лимфомы или других лимфопролиферативных нарушений, св¤занных с вирусом Ёпштейна-Ѕарр.

Ёстрогены (включа¤ пероральные эстрогенсодержащие контрацептивы) снижают клиренс v —, удлин¤ют период полувыведени¤ и их терапевтические и токсические эффекты. ѕо¤влению гирсутизма и угрей способствует одновременное применение других стероидных гормональных лекарственных средств - андрогенов, эстрогенов, анаболических стероидов, пероральных контрацептивов.

“рициклические антидепрессанты могут усиливать выраженность депрессии, вызванной приемом дексаметазона (не показаны дл¤ терапии данных побочных эффектов).

–иск развити¤ катаракты повышаетс¤ при применении на фоне других v —, антипсихотических лекарственных средств (нейролептиков), карбутамида и азатиоприна. ќдновременное применение с м-холиноблокаторами (включа¤ антигистаминные лекарственные средства, трициклические антидепрессанты), нитратами способствует развитию повышени¤ внутриглазного давлени¤.

ѕри одновременном применении с фторхинолонами повышаетс¤ риск возникновени¤ тендопатии (преимущественно ахиллова сухожили¤) у пациентов пожилого возраста и у пациентов с заболевани¤ми сухожилий.

ѕротивомал¤рийные средства (хлорохин, гидроксихлорохин, мефлохин) в сочетании с дексаметазоном могут повышать риск развити¤ миопатии, кардиомиопатии.

»нгибиторы ангиотензинпревращающего фермента при одновременном применении с дексаметазоном могут измен¤ть состав периферической крови.

The simultaneous use of inhibitors of the isoenzyme CYP3A, including drugs containing cobicistat, may increase the risk of developing systemic side effects. Simultaneous use should be avoided except in cases where the benefits of use outweigh the risk of developing systemic side effects of GCS, in which case patients should be monitored for the development of systemic side effects of GCS.