Dexamethasone Renewal pills 0.5 mg, 56 pcs.

Composition

Active ingredient:Dexamethasone-0.0005 g, Excipients: before receiving a tablet weighing 0.15 g potato starch – 0.0340 g, sucrose (sugar) – 0.1140 g, stearic acid – 0.0015 g.

Pharmacological action

Dexamethasone is a synthetic glucocorticosteroid (GCS), a methylated derivative of fluoroprednisolone. It has anti-inflammatory, anti-allergic, desensitizing, immunosuppressive, anti-shock and antitoxic effects. Inhibits the secretion of thyroid-stimulating hormone and follicle-stimulating hormone. Increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases the number of red blood cells (stimulates the production of erythropoietins). It interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus, stimulates the synthesis of matrix ribonucleic acid (mRNA); the latter induces the formation of proteins, including lipocortin, that mediate cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid, and suppresses the synthesis of endoperoxides, prostaglandins, and leukotrienes that contribute to inflammation, allergies, and others. Effect on protein metabolism: reduces the amount of protein in plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumins in the liver and kidneys; increases protein catabolism in muscle tissue. Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat 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, which leads to an increase in glucose intake from the liver to the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, which leads to the activation of gluconeogenesis. Effect on water and electrolyte metabolism: detains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticosteroid activity), reduces the absorption of calcium ions from the gastrointestinal tract, “washes” calcium ions from the bones, increases the excretion of calcium ions by the kidneys. The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; induction of the formation of lipocortins 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). The anti-allergic effect develops as a result of suppressing the synthesis and secretion of allergy mediators, inhibiting the release of histamine and other biologically active substances from sensitized mast cells and basophils, reducing the number of circulating basophils, suppressing the development of lymphoid and connective tissue, reducing the number of T – and B-lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, and changing the body’s immune response. In chronic obstructive pulmonary disease, the action is mainly based on inhibiting inflammatory processes, inhibiting the development or prevention of edema of the mucous membranes, inhibiting eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibiting erosion and desquamation of the mucous membrane. 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. Anti-shock and antitoxic effects are associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenoreceptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane – protective properties, and activation of liver enzymes involved in the metabolism of endo-and xenobiotics. The immunosuppressive effect is caused by inhibition of the release of cytokines (interleukin-1, interleukin-2, interferon gamma) from lymphocytes and macrophages. Inhibits the synthesis and secretion of adrenocorticotropic hormone (ACTH), and secondarily-the synthesis of endogenous corticosteroids. The peculiarity of the action is a significant inhibition of pituitary function and almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg / day inhibit the adrenal cortex; the biological half-life is 32-72 hours (the duration of suppression of the hypothalamic-pituitary-adrenal cortex system). In terms of glucocorticoid activity,0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone,15 mg of hydrocortisone, or 17.5 mg of cortisone for oral dosage forms. Pharmacokineticsabsorption After oral administration is rapidly and completely absorbed, the maximum concentration of dexamethasone in blood plasma is 1-2 hours. Blood distribution binds (60-70%) to a specific carrier protein, transcortin. It easily passes through histohematic barriers (including the blood-brain and placental barriers). Metabolismmetabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. Excretion is eliminated by the kidneys (a small amount of dexamethasone passes into breast milk). The elimination half-life is 3-5 hours.

Indications

• Systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis).
• Acute and chronic inflammatory diseases of the joints: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, scapular periarthritis, ankylosing spondylitis (Ankylosing spondylitis), juvenile arthritis, Still’s syndrome in adults, bursitis, non-specific tendosynovitis, synovitis and epicondylitis.
• Rheumatic fever, acute rheumocarditis.
• Acute and chronic allergic diseases: allergic reactions to medicines and food, serum sickness, urticaria, allergic rhinitis, angioedema, medicinal exanthema, pollinosis.
• Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (with damage to a large surface of the skin), toxidermia, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell’s syndrome), bullous herpetiform dermatitis, malignant exudative erythema (Stevens-Johnson syndrome).
• Brain edema (only after confirmation of symptoms of increased intracranial pressure by results of magnetic resonance imaging or computed tomography) caused by a brain tumor and/or associated with surgery or radiation damage.
• Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.
• Inflammatory diseases of the eyes: sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis.
• Primary or secondary adrenal insufficiency (including the condition after removal of the adrenal glands).
• Congenital adrenal hyperplasia.
• Autoimmune kidney diseases (including acute glomerulonephritis); nephrotic syndrome.
• Subacute thyroiditis.
• Hematopoietic diseases – agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho-and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.
• Lung diseases: acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis. Bronchial asthma (in bronchial asthma, the drug is prescribed only for severe cases, ineffectiveness or inability to take inhaled corticosteroids).
• Tuberculosis meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).
• Berylliosis, Leffler’s syndrome (not amenable to other therapy).
• Lung cancer (in combination with cytostatics).
• Multiple sclerosis.
• Diseases of the gastrointestinal tract: ulcerative colitis, Crohn’s disease, local enteritis.
• Hepatitis.
• Prevention of graft rejection reaction as part of complex therapy.
• Hypercalcemia on the background of cancer, nausea and vomiting during cytostatic therapy.
• Myeloma disease.
• Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.

Use during pregnancy and lactation

Dexamethasone passes through the placenta (can reach high concentrations in the fetus) and into breast milk. During pregnancy, especially in the first trimester, or in women planning pregnancy, the use of Dexamethasone is indicated only if the expected therapeutic effect exceeds the risk of negative effects on the mother or fetus. Corticosteroids should be prescribed during pregnancy only for absolute indications. With long-term therapy during pregnancy, the possibility of fetal disorders is not excluded. If used in the third trimester of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn. If it is necessary to carry out treatment with the drug during breastfeeding, then breast-feeding should be discontinued.

Contraindications

For short-term use for “vital” indications, the only contraindication is hypersensitivity; systemic mycosis; simultaneous use of live and weakened vaccines with immunosuppressive doses of the drug; sucrose intolerance, isomaltase/sucrose deficiency, glucose-galactose malabsorption; breast-feeding period; children under 3 years of age. With caution, parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transmitted, including recent contact with the patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles; amoebiasis, strongyloidosis (established or suspected); active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific antimicrobial therapy. Pre-and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency conditions (including acquired immunodeficiency syndrome or human immunodeficiency virus (HIV infection)). Diseases of the gastrointestinal tract: peptic ulcer of the stomach and duodenum 12, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess formation, diverticulitis. Diseases of the cardiovascular system, including recent myocardial infarction (in patients with acute and subacute myocardial infarction, necrosis may spread, scar tissue formation may slow down and, as a result, rupture of the heart muscle), decompensated chronic heart failure (CHF), arterial hypertension, hyperlipidemia. Endocrine diseases – diabetes mellitus (including impaired tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itsenko-Cushing’s disease, obesity (stage III-IV). Severe chronic renal and / or hepatic insufficiency, nephrourolithiasis. Hypoalbuminemia and conditions predisposing to its occurrence. Systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open-and closed-angle glaucoma. Use of the drug in elderly patients (due to a high risk of developing osteoporosis and arterial hypertension). Acute psychosis, severe affective disorders (including in the anamnesis). An eye infection caused by the herpes simplex virus (due to the risk of corneal perforation). During pregnancy. In children during the growth period, corticosteroids should be used only for absolute indications and under the careful supervision of the attending physician.

Side effects

The frequency of development and severity of side effects depend on the duration of use, the amount of dose used and the possibility of observing the circadian rhythm of administration. Dexamethasone is usually well tolerated. It has a low mineralocorticoid activity, that is, its effect on water-electrolyte metabolism is small. As a rule, low and medium doses of dexamethasone do not cause sodium and water retention in the body, increased potassium excretion. The following side effects are described:Endocrine system disorders: reduced glucose tolerance, “steroid” diabetes mellitus or latent diabetes mellitus, adrenal suppression, Itsenko-Cushing syndrome (moon-shaped face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children. Disorders of the blood and lymphatic system: moderate leukocytosis, leukocyturia, lymphopenia, eosinopenia, polycythemia. Gastrointestinal disorders: nausea, vomiting, abdominal pain, epigastric discomfort, pancreatitis, “steroid” ulcers of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the stomach and intestinal wall, increased or decreased appetite, flatulence, hiccups. In rare cases-increased activity of “hepatic” transaminases and alkaline phosphatase. Cardiac and vascular disorders: 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 the formation of scar tissue, which can lead to rupture of the heart muscle. Nervous system disorders: increased intracranial pressure, pseudotumor of the cerebellum, headache, convulsions. Mental disorders: nervousness or restlessness, insomnia, emotional lability, delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, suicidal tendencies. Visual disorders: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eye, trophic changes in the cornea, exophthalmos, corneal perforation, central serous chorioretinopathy. Hearing disorders and labyrinth disorders: dizziness, vertigo. Metabolic and nutritional disorders: hypercholesterolemia, increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, epidural lipomatosis. Due to mineralocorticosteroid activity-fluid retention and sodium ions (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue). Musculoskeletal and connective tissue disorders: slowing of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, “steroid” myopathy, decreased muscle mass (atrophy). Skin and subcutaneous tissue disorders: delayed wound healing, petechiae, ecchymosis, thinning of the skin, atrophy of the skin and subcutaneous tissue, hyper – or hypopigmentation, “steroid” acne, striae, tendency to develop pyoderma and candidiasis, skin pigmentation disorders (hypo – or hyperpigmentation), telangiectasia. Immune system disorders: generalized (skin rash, itchy skin, anaphylactic shock), local allergic reactions. Infectious and parasitic diseases: the development or exacerbation of infections (the appearance of this side effect is promoted by jointly used immunosuppressants and vaccination), masking infections. General disorders and disorders at the injection site: withdrawal syndrome.

Interaction

Dexamethasone increases the toxicity of cardiac glycosides (due to the resulting hypokalemia, the risk of arrhythmias increases). Accelerates the elimination of acetylsalicylic acid, reduces its concentration in the blood (when dexamethasone is discontinued, the concentration of salicylates in the blood increases and the risk of side effects increases). Concomitant use with live antiviral vaccines and other types of immunizations increases the risk of virus activation and infection. Increases the metabolism of isoniazid, mexiletine (especially in “fast acetylators”), which leads to a decrease in their plasma concentrations. Increases the risk of developing hepatotoxic effects of paracetamol (induction of “liver” enzymes and formation of a toxic metabolite of paracetamol). Increases (with long-term therapy) the content of folic acid. Hypokalemia caused by corticosteroids may increase the severity and duration of muscle block with muscle relaxants. In high doses, it reduces the effect of somatropin. Antacids reduce the absorption of corticosteroids. Dexamethasone reduces the effect of hypoglycemic drugs; enhances the anticoagulant effect of coumarin derivatives. Weakens the effect of vitamin D on the absorption of calcium ions in the intestinal lumen. Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by corticosteroids. Reduces the concentration of praziquantel in the blood. Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity. Thiazide diuretics, carbonic anhydrase inhibitors, other corticosteroids, and amphotericin B increase the risk of hypokalemia, while sodium – containing medications increase the risk of edema and high blood pressure. Nonsteroidal anti-inflammatory drugs and ethanol increase the risk of ulceration of the gastrointestinal mucosa, bleeding, in combination with nonsteroidal anti-inflammatory drugs for the treatment of arthritis, it is possible to reduce the dose of corticosteroids due to the summation of the therapeutic effect. Indomethacin, by displacing dexamethasone from the albumin bond, increases the risk of side effects. Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis. The therapeutic effect of corticosteroids decreases under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of” hepatic ” microsomal enzymes (increased metabolic rate). Mitotan and other inhibitors of adrenal cortex function may cause the need to increase the dose of corticosteroids. The clearance of corticosteroids increases against the background of thyroid hormones. Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus. Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of corticosteroids, prolong the half-life and their therapeutic and toxic effects. The appearance of hirsutism and acne is promoted by the simultaneous use of other steroid hormonal drugs-androgens, estrogens, anabolic steroids, oral contraceptives.Tricyclic antidepressants may increase the severity of depression caused by dexamethasone (not indicated for the treatment of these side effects). The risk of developing cataracts increases when used against the background of other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine. Concomitant administration with m-holinoblokatorami (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure. When used concomitantly with fluoroquinolones, the risk of tendopathy (mainly Achilles tendon) increases in elderly patients and in patients with tendon diseases. Antimalarials (chloroquine, hydroxychloroquine, mefloquine) in combination with dexamethasone may increase the risk of developing myopathy, cardiomyopathy. Angiotensin-converting enzyme inhibitors, when administered concomitantly with dexamethasone, may alter the composition of peripheral blood.

How to take, course of administration and dosage

Inside, in individually selected doses, the value of which is determined by the type of disease, the degree of its activity and the nature of the patient’s response. The average daily dose is 0.75-9 mg. In severe cases, large doses can also be used, divided into 3-4 doses. The maximum daily dose is usually 15 mg. After the therapeutic effect is achieved, the dose is gradually reduced (usually by 0.5 mg in 3 days) to a maintenance dose of 2-4.5 mg / day. The minimum effective dose is 0.5-1 mg / day. Children (depending on their age) are prescribed 83.3-333.3 mcg / kg or 2.5-10 mg / sq. m / day in 3-4 doses. The duration of use of dexamethasone depends on the nature of the pathological process and the effectiveness of treatment and ranges from several days to several months or more. Treatment is stopped gradually (at the end, several corticotropin injections are prescribed). For bronchial asthma, rheumatoid arthritis, ulcerative colitis-1.5-3 mg / day; for systemic lupus erythematosus-2-4.5 mg/day; for oncohematological diseases-7.5-10 mg. For the treatment of acute allergic diseases, it is advisable to combine parenteral and oral administration: 1 day-4-8 mg parenterally; 2 day-inside,4 mg 3 times a day; 3,4 day-inside,4 mg 2 times a day; 5,6 day-4 mg / day, inside; 7 day-drug withdrawal. Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. With a small test, dexamethasone is given to the patient 0.5 mg every 6 hours during the day (that is, at 8 o’clock in the morning, at 14 o’clock,20 o’clock and 2 o’clock in the morning). Urine for the determination of 17-oxycorticosteroids or free cortisol is collected from 8 am to 8 am 2 days before the appointment of dexamethasone and also 2 days in the same time intervals after taking the specified doses of dexamethasone. These doses of dexamethasone inhibit the formation of corticosteroids in almost all healthy individuals.6 hours after the last dose of dexamethasone, the plasma cortisol level is below 135-138 nmol / l (less than 4.5-5 mcg/100 ml). A decrease in the excretion of 17-oxycorticosteroids below 3 mg / day, and free cortisol below 54-55 nmol/day (below 19-20 mcg/day) excludes hyperfunction of the adrenal cortex. In individuals suffering from Itsenko-Cushing’s disease or syndrome, no changes in corticosteroid secretion are observed during the small test. When performing a large test, dexamethasone is prescribed 2 mg every 6 hours for 2 days (that is,8 mg of dexamethasone per day). Urine is also collected to determine 17-hydroxycorticosteroids or free cortisol (if necessary, determine free cortisol in plasma). In Itsenko-Cushing’s disease, there is a decrease in the excretion of 17-oxycorticosteroids or free cortisol by 50% or more, while in adrenal tumors or adrenocorticotropic-ectopic (or corticoliberin-ectopic) syndrome, corticosteroid excretion does not change. In some patients with adrenocorticotropic-ectopic syndrome, a decrease in corticosteroid excretion is not detected even after taking dexamethasone at a dose of 32 mg / day.

Overdose

Possible increase in dose-dependent side effects, with the exception of allergic reactions. It is necessary to reduce the dose of dexamethasone.

Treatment: symptomatic.

Special instructions

When prescribing dexamethasone for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat specific antibacterial therapy when using the drug in patients with latent tuberculosis, lymphadenitis after BCG vaccination, polio, acute and chronic bacterial, parasitic infections; specific therapy in patients with peptic ulcer of the stomach and/or intestines, osteoporosis. When used daily, atrophy of the adrenal cortex develops by 5 months of treatment. It may mask some of the symptoms of infections; during treatment, it is useless to carry out immunization. Sudden withdrawal of corticosteroids, especially in the case of previous use of high doses, leads to a syndrome of “withdrawal” of corticosteroids (not due to hypocorticism): decreased appetite, nausea, lethargy, generalized musculoskeletal pain, asthenia, and acute adrenal insufficiency may also occur (low blood pressure, arrhythmia, sweating, weakness, oligoanuria, vomiting, abdominal pain, diarrhea, hallucinations, fainting, coma). After withdrawal, relative insufficiency of the adrenal cortex persists for several months. If stressful situations occur during this period, they are prescribed (according to indications) for the duration of corticosteroids, if necessary in combination with mineralocorticosteroids. The dose of dexamethasone should 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, it is necessary to carefully monitor the dynamics of growth and development. Children who have been in contact with measles or chickenpox patients during treatment are prescribed specific immunoglobulins as a preventive measure. During treatment with dexamethasone (especially long-term), it is necessary to monitor the optometrist, monitor blood pressure and water-electrolyte balance, as well as the picture of peripheral blood and blood glucose concentration. In order to reduce side effects, you can prescribe anabolic steroids, antacids, and increase the intake of potassium ions in the body (eating foods rich in potassium and calcium, or taking potassium, calcium, and vitamin D preparations). Food should be rich in protein, vitamins, and a small amount of fat, carbohydrates, and salt. In children during the growth period, corticosteroids should be used only for absolute indications and under the 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 activation of strongyloidosis increases. During therapy with the drug, careful monitoring of the condition of patients with CHF, uncontrolled arterial hypertension, corneal injuries and ulcerative lesions, glaucoma is necessary. Myasthenia gravis may worsen. Against the background of the use of corticosteroids, a change in sperm motility is possible. Taking the drug may mask the symptoms of “peritoneal irritation” in patients with perforation of the stomach or intestinal wall. The effect of the drug is enhanced in patients with cirrhosis of the liver. It should be taken into account that dexamethasone clearance decreases in patients with hypothyroidism, and increases in patients with thyrotoxicosis. In patients with diabetes mellitus, blood glucose concentrations should be monitored and, if necessary, the dose of hypoglycemic drugs should be adjusted. Influence on the ability to drive vehicles and mechanicsmuch as possible side effects during therapy with Dexamethasone, care should be taken when driving vehicles and working with mechanisms, engaging in other activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 4 years.

Active ingredient

Dexamethasone

Conditions of release from pharmacies

By prescription

Dosage form

of the tablet

Weight

Weight: 24 gr.