The drug dexamethasone, whose successful clinical trials the head of WHO called a scientific breakthrough, can indeed be effective for patients in intensive care. It suppresses immune activity and stops the “cytokine storm” from which many people infected with COVID-19 are dying today. However, it should never be taken by people with mild to moderate symptoms of the disease, scientists warn. If a person starts using it ahead of time, he will simply destroy his immune system and it will be almost impossible to save him. Also, with long-term use, this anti-inflammatory drug can cause obesity, diabetes, osteoporosis, glaucoma and even mental disorders. Therefore, the drug should be used with great caution under strict medical supervision.
Composition and release form
Tablets - 1 tablet:
- Active ingredient: Dexamethasone – 0.0005 g
- Excipients: potato starch – 0.0340 g; sucrose (sugar) – 0.1140 g; stearic acid – 0.0015 g.
Tablets weighing 0.15 g.
Tablets 0.5 mg.
10, 14 tablets in a blister pack made of polyvinyl chloride film and aluminum foil.
5, 10 blister packs of 10 tablets each or 4 blister packs of 14 tablets each with instructions for use in a cardboard pack.
Clinical trials of dexamethasone for COVID-19
According to ClinicalTrials.gov, there are currently 14 studies of dexamethasone in patients with COVID-19: 9 studies are actively recruiting, 3 studies are not yet recruiting, 1 study is active but not recruiting, and 1 study has completed.
The completed study (NCT04445506) assessed the effectiveness of short-course dexamethasone on length of stay, intensive care unit transfer, and mortality in patients with COVID-19. The study included 50 patients. Dexamethasone 4 mg 3, 2, and once daily regimens for 2 days were studied. The results of the study have not been published.
Most planned studies are investigating dexamethasone in patients with acute respiratory syndrome in patients with COVID-19 at the following dosing regimens:
- 20 mg IV once daily for 5 days, then 10 mg IV once daily for 5 days (NCT04327401, NCT04360876, NCT04347980, NCT04325061);
- 16 mg IV once daily from days 1 to 5, 8 mg IV once daily from days 6 to 10 (NCT04395105).
Description of the dosage form
Tablets are white, flat-cylindrical with a chamfer.
Pharmacokinetics
Absorption
After oral administration, it is quickly and completely absorbed, the maximum concentration of dexamethasone in the blood plasma is 1-2 hours.
Distribution
In the blood it binds (60–70%) to a specific carrier protein – transcortin. Easily passes through histohematic barriers (including the blood-brain and placental barriers).
Metabolism
Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.
Removal
Excreted by the kidneys (a small amount of dexamethasone passes into breast milk). Half-life is 3-5 hours.
Pharmacodynamics
Dexamethasone is a synthetic glucocorticosteroid (GCS), a methylated derivative of fluoroprednisolone. It has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, antishock 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 erythropoietin). 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, suppresses the release of arachidonic acid and suppresses the synthesis of endoperoxides, prostaglandins, leukotrienes, which 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 albumin synthesis in the liver and kidneys; enhances protein catabolism in muscle tissue.
Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, 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, which leads to the activation of gluconeogenesis.
Effect on water-electrolyte metabolism: retains 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 out” 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; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal ones).
The 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, reducing the sensitivity of effector cells to allergy mediators, suppressing antibody formation, changing the body's immune response.
In chronic obstructive pulmonary disease, the effect is based mainly on inhibition of inflammatory processes, inhibition of development or prevention of swelling of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenergic receptors of small and medium-caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of bronchial secretions due to inhibition or reduction of its production.
Antishock 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 adrenergic receptors 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 due to inhibition of the release of cytokines (interleukin-1, interleukin-2; interferon gamma) from lymphocytes and macrophages. Suppresses the synthesis and secretion of adrenocorticotropic hormone (ACTH), and secondarily the synthesis of endogenous GCS.
The peculiarity of the action is significant inhibition of pituitary function and the almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg/day inhibit the adrenal cortex; biological half-life is 32-72 hours (duration of inhibition of the hypothalamic-pituitary-adrenal cortex system).
In terms of the strength of glucocorticoid activity, 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisolone, 15 mg of hydrocortisone or 17.5 mg of cortisone for oral dosage forms.
Publications in the media
Pharmaceutical group - glucocorticosteroid.
Pharmaceutical action. GCS is a methylated derivative of fluoroprednisolone, inhibits the release of interleukin1 and interleukin2, interferon gamma from lymphocytes and macrophages. It has anti-inflammatory, antiallergic, desensitizing, antishock, antitoxic and immunosuppressive effects. Suppresses the release of ACTH and beta-lipotropin by the pituitary gland, but does not reduce the level of circulating beta-endorphin. Inhibits the secretion of TSH and FSH. 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). Interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus and stimulates mRNA synthesis; the latter induces the formation of proteins, incl. lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and suppresses the synthesis of endoperoxides, Pg, leukotrienes, which contribute to inflammation, allergies, etc. 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 liver and kidneys; enhances protein catabolism in muscle tissue. Lipid metabolism: increases the synthesis of higher fatty acids and TG, redistributes fat (fat accumulation mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia. Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; 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. Water-electrolyte metabolism: retains Na+ and water in the body, stimulates the excretion of K+ (MCS activity), reduces the absorption of Ca2+ from the gastrointestinal tract, “washes out” Ca2+ from the 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; inducing the formation of lipocortin and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal ones). The antiallergic effect develops as a result of suppression of the synthesis and secretion of allergic 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, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, changing the body's immune response. In COPD, the action is based mainly on inhibition of inflammatory processes, inhibition of development or prevention of swelling of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenergic receptors of small and medium-caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by inhibiting or reducing its production. Antishock 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 adrenergic receptors 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 due to inhibition of the release of cytokines (interleukin1, interleukin2; interferon gamma) from lymphocytes and macrophages. Suppresses the synthesis and secretion of ACTH and, secondarily, the synthesis of endogenous corticosteroids. Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation. The peculiarity of the action is significant inhibition of pituitary function and the almost complete absence of MCS activity. Doses of 1-1.5 mg/day inhibit the adrenal cortex; biological T1/2 - 32-72 hours (duration of inhibition of the hypothalamus-pituitary-adrenal cortex system). In terms of the strength of GCS 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.
Pharmacokinetics. After oral administration, it is quickly and completely absorbed, TCmax is 1-2 hours. In the blood it binds (60-70%) to a specific carrier protein - transcortin. Easily passes through histohematic barriers (including through the BBB and placental). Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. Excreted by the kidneys (a small part by the lactating glands). T1/2 - 3-5 hours.
Indications. Systemic connective tissue diseases (SLE, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis). Acute and chronic inflammatory diseases of the joints: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, glenohumeral periarthritis, ankylosing spondylitis (Bechterew's disease), juvenile arthritis, Still's syndrome in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis . Rheumatic fever, acute rheumatic carditis. Bronchial asthma, status asthmaticus. Acute and chronic allergic diseases: allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, hay fever. Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (affecting a large surface of the skin), toxicerma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous dermatitis herpetiformis, malignant exudative erythema (syndrome) Stevens-Johnson). Brain edema (including due to a brain tumor or associated with surgery, radiation therapy or head trauma) after prior parenteral use. Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis. Inflammatory eye diseases: 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. Kidney diseases of autoimmune origin (including acute glomerulonephritis); nephrotic syndrome. Subacute thyroiditis. Diseases of the hematopoietic organs - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lymphocytic 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. Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy). Berylliosis, Loeffler's syndrome (not amenable to other therapy). Lung cancer (in combination with cytostatics). Multiple sclerosis. Gastrointestinal diseases: ulcerative colitis, Crohn's disease, local enteritis. Hepatitis. Prevention of transplant rejection. Hypercalcemia due to cancer, nausea and vomiting during cytostatic therapy. Multiple myeloma. Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
Contraindications . For short-term use for “life-saving” indications, the only contraindication is hypersensitivity.
Carefully. Parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently suffered, including recent contact with a patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidiasis (established or suspected); systemic mycosis; active and latent tuberculosis. Use for severe infectious diseases is permissible only against the background of specific therapy. Pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency conditions (including AIDS or HIV infection). Gastrointestinal diseases: gastric and duodenal ulcers, esophagitis, gastritis, acute or latent peptic ulcers, recently created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess formation, diverticulitis. Diseases of the cardiovascular system, incl. recent myocardial infarction (in patients with acute and subacute myocardial infarction, the necrosis focus may spread, the formation of scar tissue may slow down and, as a result, the heart muscle will rupture), decompensated CHF, arterial hypertension, hyperlipidemia. Endocrine diseases - diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Cushing's disease. Severe chronic renal and/or liver failure, nephrourolithiasis. Hypoalbuminemia and conditions predisposing to its occurrence. Systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (III-IV stage), poliomyelitis (except for the form of bulbar encephalitis), open- and closed-angle glaucoma, lactation period.
Dosing. Orally, in individually selected doses, the amount 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 be used, divided into 3-4 doses. The maximum daily dose is usually 15 mg. After achieving a therapeutic effect, the dose is gradually reduced (usually by 0.5 mg every 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 age) are prescribed 83.3-333.3 mg/kg or 2.5-10 mcg/sq.m/day in 3-4 doses. The duration of dexamethasone use 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 injections of corticotropin are prescribed). For bronchial asthma, rheumatoid arthritis, ulcerative colitis - 1.5-3 mg/day; for SLE - 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; Day 2 - orally, 4 mg 3 times a day; 3, 4 days - orally, 4 mg 2 times a day; 5, 6 days - 4 mg/day, orally; Day 7 - drug withdrawal. Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. For a small test, dexamethasone is given to the patient 0.5 mg every 6 hours during the day (i.e. at 8 a.m., 2 p.m., 8 p.m. and 2 a.m.). Urine for determination of 17-OX or free cortisol is collected from 8 am to 8 am 2 days before the appointment of dexamethasone and also 2 days at the same time intervals after taking the indicated doses of dexamethasone. These doses of dexamethasone inhibit the formation of corticosteroids in almost all apparently 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). Reducing the excretion of 17-OX below 3 mg/day, and free cortisol below 54-55 nmol/day (below 19-20 mcg/day) excludes hyperfunction of the adrenal cortex. In persons suffering from Cushing's disease or syndrome, no changes in the secretion of corticosteroids are observed during a small test. When conducting a large test, dexamethasone is prescribed at a dose of 2 mg every 6 hours for 2 days (i.e., 8 mg dexamethasone per day). Urine is also collected to determine 17-OX or free cortisol (if necessary, determine free cortisol in plasma). In Cushing's disease, there is a decrease in the excretion of 17-OX or free cortisol by 50% or more, while in adrenal tumors or ACTH-ectopic (or corticoliberin-ectopic) syndrome, the excretion of corticosteroids does not change. In some patients with ACTH-ectopic syndrome, a decrease in corticosteroid excretion is not detected even after taking dexamethasone at a dose of 32 mg/day.
Side effect. The incidence and severity of side effects depend on the duration of use, the size of the dose used and the ability to comply with the circadian rhythm of the prescription. From the endocrine system: decreased glucose tolerance, “steroid” diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (moon-shaped face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia, stretch marks) , delayed sexual development in children. From the digestive system: nausea, vomiting, pancreatitis, “steroid” gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups. In rare cases, there is an increase in the activity of liver transaminases and alkaline phosphatase. From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of CHF, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction - the spread of necrosis, slowing down the formation of scar tissue, which can lead to rupture of the heart muscle. From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor of the cerebellum, headache, convulsions. From the senses: 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. From the metabolic side: increased excretion of Ca2+, hypocalcemia, increased body weight, negative nitrogen balance (increased protein breakdown), increased sweating. Caused by MCS activity - fluid and Na+ retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue). From the musculoskeletal system: slowing of growth and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and femur), rupture of muscle tendons, “steroid” myopathy, decreased muscle mass (atrophy). From the skin and mucous membranes: delayed wound healing, petechiae, ecchymosis, thinning of the skin, atrophy of the skin and subcutaneous tissue, hyper- or hypopigmentation, steroid acne, stretch marks, tendency to develop pyoderma and candidiasis. Allergic reactions: generalized (skin rash, skin itching, anaphylactic shock), local allergic reactions. Other: development or exacerbation of infections (the appearance of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, “fast acetylator” syndrome), which leads to a decrease in their plasma concentrations. Increases the risk of developing the hepatotoxic effect of paracetamol (induction of “liver” enzymes and the formation of a toxic metabolite of paracetamol). Increases (with long-term therapy) the content of folic acid. Hypokalemia caused by GCS can increase the severity and duration of muscle blockade due to 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 Ca2+ in the intestinal lumen. Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by GCS. 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 Na+-containing drugs increase the risk of edema and increased blood pressure. NSAIDs and ethanol increase the risk of developing ulceration of the gastrointestinal mucosa and bleeding; in combination with NSAIDs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect. Indomethacin, displacing dexamethasone from its association with albumin, increases the risk of developing its side effects. Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis. The therapeutic effect of GCS is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “liver” microsomal enzymes (increased metabolic rate). Mitotane and other inhibitors of adrenal cortex function may necessitate an increase in the dose of GCS. The clearance of GCS 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 GCS, prolong T1/2 and their therapeutic and toxic effects. The appearance of hirsutism and acne is facilitated 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 taking corticosteroids (not indicated for the treatment of these side effects). The risk of developing cataracts increases when used in conjunction with other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine. Simultaneous administration with m-anticholinergics (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.
Special instructions. Before and during GCS therapy, it is necessary to monitor a general blood count, glycemic levels and plasma electrolyte levels. When prescribing dexamethasone for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat with bactericidal antibiotics. With daily use, atrophy of the adrenal cortex develops by 5 months of treatment. May mask some symptoms of infections; It is useless to immunize during treatment. With sudden withdrawal, especially in the case of previous use of high doses, a syndrome of “life-saving” indications occurs, taking into account the expected therapeutic effect and the negative effect on the fetus. With long-term therapy during pregnancy, fetal growth is impaired. 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. During treatment with dexamethasone (especially long-term), observation by an ophthalmologist, monitoring of blood pressure and water-electrolyte balance, as well as peripheral blood patterns and glycemic levels are necessary. In order to reduce side effects, you can prescribe anabolic steroids, antacids, and also increase the intake of K+ into the body (diet, K+ drugs). Food should be rich in K+, proteins, vitamins, and contain a small amount of fat, carbohydrates and salt. In children during the growth period, GCS should be used only according to absolute indications and under the particularly careful supervision of the attending physician.
Indications for use of Dexamethasone
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, glenohumeral periarthritis, ankylosing spondylitis (ankylosing spondylitis), juvenile arthritis, syndrome
Stilla in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis.
Rheumatic fever, acute rheumatic carditis.
Acute and chronic allergic diseases: allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, hay fever.
Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (affecting a large surface of the skin), toxicerma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous dermatitis herpetiformis, malignant exudative erythema (syndrome) Stevens-Johnson).
Brain edema (only after confirmation of symptoms of increased intracranial pressure by magnetic resonance or computed tomography) caused by a brain tumor and/or associated with surgery or radiation injury.
Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.
Inflammatory eye diseases: 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.
Kidney diseases of autoimmune origin (including acute glomerulonephritis); nephrotic syndrome.
Subacute thyroiditis.
Diseases of the hematopoietic organs - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lymphoid 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 (for bronchial asthma, the drug is prescribed only in severe cases, ineffectiveness or inability to take inhaled corticosteroids).
Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).
Berylliosis, Loeffler's syndrome (not amenable to other therapy).
Lung cancer (in combination with cytostatics).
Multiple sclerosis.
Gastrointestinal diseases: ulcerative colitis, Crohn's disease, local enteritis.
Hepatitis.
Prevention of transplant rejection as part of complex therapy.
Hypercalcemia due to cancer, nausea and vomiting during cytostatic therapy.
Multiple myeloma.
Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
Contraindications to the use of Dexamethasone
- For short-term use for “life-saving” indications, the only contraindication is hypersensitivity; systemic mycosis;
- simultaneous use of live and attenuated vaccines with immunosuppressive doses of the drug;
- sucrose intolerance, isomaltase/sucrase deficiency, glucose-galactose malabsorption; breastfeeding period; children up to 3 years old.
Carefully:
Parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently suffered, including recent contact with a patient) –
- herpes simplex, herpes zoster (viremic phase), chicken pox, measles;
- amebiasis, strongyloidiasis (established or suspected);
- active and latent tuberculosis.
Use of Dexamethasone during pregnancy and children
Dexamethasone crosses 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 outweighs the risk of negative effects on the mother or fetus. GCS should be prescribed during pregnancy only for absolute indications. With long-term therapy during pregnancy, the possibility of fetal damage cannot be 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, breastfeeding should be stopped.
Side effects of Dexamethasone
The incidence and severity of side effects depend on the duration of use, the size of the dose used and the ability to comply with the circadian rhythm of the prescription. Dexamethasone is usually well tolerated. It has low mineralocorticoid activity, that is, its effect on water and electrolyte metabolism is small. As a rule, low and medium doses of dexamethasone do not cause sodium and water retention in the body or increased potassium excretion.
- Endocrine system disorders: decreased glucose tolerance, “steroidal” diabetes mellitus or manifestation of latent diabetes mellitus, suppressed adrenal function, Itsenko-Cushing syndrome (moon face, pituitary type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delayed sexual development in children.
- Blood and lymphatic system disorders: moderate leukocytosis, leukocyturia, lymphopenia, eosinopenia, polycythemia.
- Gastrointestinal tract disorders: nausea, vomiting, abdominal pain, discomfort in the epigastric region, pancreatitis, “steroid” gastric and duodenal ulcers, erosive esophagitis, bleeding and perforation of the stomach and intestinal wall, increased or decreased appetite , flatulence, hiccups. In rare cases, increased activity of liver transaminases and alkaline phosphatase.
- Disorders of 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 necrosis focus spreads, the formation of scar tissue slows down, which can lead to rupture of the heart muscle.
- Nervous system disorders: increased intracranial pressure, cerebellar pseudotumor, headache, convulsions.
- Mental disorders: nervousness or anxiety, 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 eye infections, trophic changes in the cornea, exophthalmos, corneal perforation, central serous chorioretinopathy.
- Hearing and labyrinthine 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. Caused by mineralocorticosteroid activity - fluid and sodium ion retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).
- Disorders of the musculoskeletal and connective tissue: slowing of growth and ossification processes in children (premature closure of the epiphyseal growth plates), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and femur), rupture of muscle tendons, "steroid" myopathy, decreased muscle mass (atrophy).
- Disorders of the skin and subcutaneous tissues: delayed healing of wounds, petechiae, ecchymoses, thinning of the skin, atrophy of the skin and subcutaneous tissue, hyper- or hypopigmentation, “steroid” acne, stretch marks, a tendency to develop pyoderma and candidiasis, impaired skin pigmentation (hypo- or hyperpigmentation), telangiectasia.
- Immune system disorders: generalized (skin rash, skin itching, anaphylactic shock), local allergic reactions.
- Infectious and parasitic diseases: development or exacerbation of infections (the appearance of this side effect is facilitated by jointly used immunosuppressants and vaccination), masking of infections.
- General disorders and disorders at the injection site: withdrawal syndrome.
Drug interactions
Dexamethasone increases the toxicity of cardiac glycosides (due to the resulting hypokalemia, the risk of developing 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).
When used simultaneously with live antiviral vaccines and against the background of other types of immunizations, it increases the risk of viral activation and the development of infections.
Increases the metabolism of isoniazid, mexiletine (especially in “fast acetylators”), which leads to a decrease in their plasma concentrations.
Increases the risk of developing the hepatotoxic effect of paracetamol (induction of “liver” enzymes and the formation of a toxic metabolite of paracetamol).
Increases (with long-term therapy) the content of folic acid.
Hypokalemia caused by GCS can increase the severity and duration of muscle blockade due to 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 GCS.
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, sodium-containing drugs - edema and increased blood pressure.
Non-steroidal anti-inflammatory drugs and ethanol increase the risk of developing ulceration of the gastrointestinal mucosa and bleeding; in combination with non-steroidal anti-inflammatory drugs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect.
Indomethacin, displacing dexamethasone from its association with albumin, increases the risk of developing its side effects.
Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis.
The therapeutic effect of GCS is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “liver” microsomal enzymes (increased metabolic rate).
Mitotane and other inhibitors of adrenal function may necessitate an increase in the dose of GCS.
The clearance of GCS increases against the background of thyroid hormones.
Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with 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 facilitated 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 taking dexamethasone (not indicated for the treatment of these side effects).
The risk of developing cataracts increases when used in conjunction with other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.
Simultaneous administration with m-anticholinergics (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.
When used simultaneously with fluoroquinolones, the risk of tendonopathy (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 and cardiomyopathy.
Angiotensin-converting enzyme inhibitors, when administered concomitantly with dexamethasone, can change the composition of peripheral blood.
Instructions for use DEXAMETHASON solution
Allergic reactions may occur (although rarely) during parenteral use of corticoids. Appropriate measures should be taken before starting treatment, taking into account this possibility (especially in patients with a history of allergic reactions to any drugs).
Patients undergoing long-term treatment with dexamethasone may experience corticoid withdrawal syndrome. Therefore, the dosage of dexamethasone should be gradually reduced.
If during therapy or when discontinuing a drug the patient is exposed to unexpected stress (trauma, surgery or serious illness), then the dose of dexamethasone should be increased or hydrocortisone or cortisone prescribed. In patients who have experienced severe stress after discontinuation of long-term dexamethasone, dexamethasone should be restarted as induced adrenal insufficiency may persist for several months after discontinuation of treatment.
Treatment with dexamethasone or natural glucocorticoids may mask signs of existing or new infection and signs of interstitial perforation.
Dexamethasone can aggravate the course of systemic fungal infections, latent amebiasis and pulmonary tuberculosis.
In patients with active pulmonary tuberculosis, dexamethasone should be prescribed (in combination with antituberculosis therapy) in cases of fulminant or severe disseminated pulmonary tuberculosis. Patients with inactive tuberculosis who are taking dexamethasone or patients with a positive tuberculin test should receive chemoprophylaxis.
Particular caution and close medical monitoring should be performed in patients with osteoporosis, hypertension, heart failure, tuberculosis, glaucoma, liver failure, renal failure, diabetes, active gastric and duodenal ulcers, recent intestinal anastomosis, ulcerative colitis and epilepsy. Particular attention should be paid to patients in the first weeks after myocardial infarction, as well as patients with thromboembolism, asthenic bulbar palsy, glaucoma, hypothyroidism, psychosis or psychoneurosis, and elderly patients.
During treatment with dexamethasone, an exacerbation of diabetes or a transition from a latent form to the form of clinical manifestations of diabetes may occur.
During long-term treatment, it is necessary to monitor serum potassium levels. Vaccination with live vaccines is contraindicated during treatment with dexamethasone. Immunization with killed viral or bacterial vaccines does not lead to the expected increase in antibodies and does not have the expected protective effect. Dexamethasone is usually not prescribed 8 weeks before and 2 weeks after vaccination. Patients receiving or taking high doses of dexamethasone for a long time should avoid contact with people with measles; In case of accidental contact, prophylactic treatment with immunoglobulin is recommended. Caution is advised in patients recovering from recent surgery and a bone fracture, as dexamethasone may delay the healing of wounds and fractures.
The effect of glucocorticoids is potentiated in patients with liver cirrhosis or hypothyroidism. Intra-articular administration of corticoids can cause local and systemic effects. Frequent use may cause damage to articular cartilage and bone necrosis.
Before intra-articular injection, synovial fluid should be evacuated from the joint and examined (for possible infection). Injecting corticosteroids into infected joints should be avoided. If septic inflammation of the joint develops after the injection, then appropriate antibacterial treatment must be started.
Patients should be informed that it is necessary to avoid putting stress on the joints into which the injection was performed until the inflammatory process has completely resolved.
Injections into unstable joints are not recommended. Corticosteroids may interfere with allergy skin test results. Dexamethasone is used in children and adolescents only under strict indications. During treatment with dexamethasone, the growth and development of children and adolescents should be carefully monitored.
Special information about some of the ingredients of the drug.
This drug contains less than 1 mmol (23 mg) sodium per dose, which is a negligible amount.
Pregnancy and lactation.
Dexamethasone should be prescribed to pregnant women only in selected urgent cases when the expected benefit to the mother justifies the risk to the fetus.
Particular care should be taken in case of preeclampsia. According to general recommendations for glucocorticoid treatment during pregnancy, the lowest effective dose to control the underlying disease should be used.
Glucocorticoids are excreted in small quantities in breast milk. Therefore, breastfeeding is not recommended for mothers taking dexamethasone, especially when using high physiological doses (about 1 mg). This can lead to fetal growth retardation and decreased secretion of endogenous corticosteroids.
Impact on the ability to drive a car or use other machinery.
Dexamethasone does not affect the ability to drive a car or operate machinery.
Dexamethasone dosage
Orally, in individually selected doses, the amount 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 be used, divided into 3-4 doses. The maximum daily dose is usually 15 mg. After achieving a therapeutic effect, the dose is gradually reduced (usually by 0.5 mg every 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 age) are prescribed 83.3-333.3 mcg/kg or 2.5-10 mg/sq.m/day in 3-4 doses.
The duration of dexamethasone use 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 injections of corticotropin 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; Day 2 – orally, 4 mg 3 times a day; 3, 4 days – orally, 4 mg 2 times a day; 5, 6 days – 4 mg/day, orally; Day 7 – drug withdrawal.
Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. For a small test, dexamethasone is given to the patient 0.5 mg every 6 hours during the day (that is, at 8 a.m., 2 p.m., 8 p.m., and 2 a.m.). Urine for the determination of 17-hydroxycorticosteroids or free cortisol is collected from 8 a.m. to 8 a.m. 2 days before the administration of dexamethasone and also 2 days at the same time intervals after taking the indicated doses of dexamethasone. These doses of dexamethasone inhibit the formation of corticosteroids in almost all apparently healthy individuals. 6 hours after the last dose of dexamethasone, plasma cortisol levels are below 135-138 nmol/l (less than 4.5-5 mcg/100 ml). Reducing the excretion of 17-hydroxycorticosteroids below 3 mg/day, and free cortisol below 54-55 nmol/day (below 19-20 mcg/day) excludes hyperfunction of the adrenal cortex. In persons suffering from Cushing's disease or syndrome, no changes in the secretion of corticosteroids are observed during a small test.
When conducting a large test, dexamethasone is prescribed 2 mg every 6 hours for 2 days (that is, 8 mg dexamethasone per day). Urine is also collected to determine 17-hydroxycorticosteroids or free cortisol (if necessary, determine free cortisol in plasma). With Itsenko-Cushing's disease, there is a decrease in the excretion of 17-hydroxycorticosteroids or free cortisol by 50% or more, while with adrenal tumors or adrenocorticotropic-ectopic (or corticoliberin-ectopic) syndrome, the excretion of corticosteroids does not change. In some patients with adrenocorticotropic-ectopic syndrome, a decrease in the excretion of corticosteroids is not detected even after taking dexamethasone at a dose of 32 mg/day.
Breakthrough from the past
Effective: 35 regions will receive the first batches of Avifavir
Deliveries will be made in two weeks
Immunosuppressants, which include the anti-inflammatory drug dexamethasone, can help fight severe coronavirus infection. As Oleg Batishchev, deputy director for scientific work at the Institute of Physics and Chemistry of the Russian Academy of Sciences, told Izvestia, this remedy helps with complications caused by overactivity of the immune system (the so-called cytokine storm).
— As far as I know, quite a lot of drugs were tested that were supposed to help combat the development of this path of the disease. “All of them have existed for a long time, and they were used in the treatment of a number of other, mainly autoimmune, pathologies,” the scientist said. “The fact that dexamethasone showed its effectiveness is certainly an important finding. I hope this will help treat severe forms of COVID-19.
Researchers at the University of Oxford previously announced breakthrough results. A report on their website suggests that inexpensive and long-established dexamethasone reduces mortality in hospitalized patients with severe respiratory complications of COVID-19. British infectious disease specialists conducted a randomized trial in which 2,104 patients received 6 mg of this drug once a day (in tablet form or intravenously) for ten days.
Photo: tass/dpa/Marcel Kusch
The results were so impressive that WHO immediately reported them. This is despite the fact that the study itself has not yet been published. The WHO Director General called the data on the effectiveness of dexamethasone a “scientific breakthrough.” According to him, the anti-inflammatory drug reduces the risk of death of patients with COVID-19 connected to ventilators by 35%. And among patients receiving oxygen - by 20%.
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Dexamethasone has been widely used since the 1980s. This is a medicine from the group of glucocorticosteroids, which has a pronounced anti-inflammatory, antiallergic, decongestant and immunosuppressive (suppressing immunity) effect on the body. The product is of synthetic origin; in fact, it is an analogue of a person’s own hormones secreted by the adrenal glands. It suppresses the functions of tissue macrophages and also limits the migration of leukocytes to the area of inflammation. As experts emphasize, the use of this drug is dangerous, since all steroids have a large number of serious side effects.
