Dexamethasone, tablets 0.5 mg 10 pcs

Pharmacotherapeutic group: glucocorticosteroid

ATC code: H02AB02

Pharmacological properties

Pharmacodynamics

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

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

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

Effect on protein metabolism: reduces the amount of protein in the plasma (at the expense of globulins) with an increase in albumin/globulin ratio, increases the synthesis of albumin in the liver and kidneys, increases 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 hypercholesterolemia.

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

Effect on water-electrolyte metabolism: inhibits sodium ions (Na+ ) and water in the body, stimulates the excretion of potassium ions (K + ) (mineralocorticosteroid (MCC) activity), reduces the absorption of calcium ions (Ca2 +) from the gastrointestinal tract, “washes” Ca2 + from the bones, increases Ca2 + excretion by the kidneys.

Anti-inflammatory activity is associated with inhibition of eosinophils release of inflammatory mediators, induction of lipocortin formation and reduction of mast cells producing hyaluronic acid, reduction of capillary permeability, stabilization of cell membranes and organelle membranes (especially lysosomal).

Antianallergic action results from inhibition of allergy mediators synthesis and secretion, inhibition of histamine and other bioactive substances release from sensitized mast cells and basophils, reduction of circulating basophils number, suppression of lymphoid and connective tissue development, reduction of T- and B-lymphocytes quantity and mast cells, reduction of effector cells sensitivity to allergy mediators, inhibition of antibody formation, immune response alteration.

In chronic obstructive pulmonary disease (COPD) the action is mainly based on inhibition of inflammatory processes, inhibition or prevention of mucous membrane edema, inhibition of eosinophilic infiltration of submucous layer of bronchial epithelium, deposition of circulating immune complexes in bronchial mucosa, and inhibition of mucous membrane erosion and desquamation. It increases sensitivity of small and medium caliber bronchial beta-adrenoreceptors to endogenous catecholamines and exogenous sympathomimetics, decreases bronchial secretion viscosity by inhibiting or reducing its production.

Antishock and antitoxic action is associated with increase of arterial pressure (BP) (due to increase in concentration of circulating catecholamines and restoration of adrenoreceptors sensitivity to them as well as vasoconstriction), reduction of vascular wall permeability, membrane-protective properties, activation of liver enzymes involved in metabolism of endo- and xenobiotics. Immunosuppressive effect is caused by inhibition of release of cytokines (interleukin-1, interleukin-2, interferon gamma) from lymphocytes and macrophages. Inhibits the synthesis and secretion of ACTH, and secondary to the synthesis of endogenous GCS. Inhibits connective tissue reactions in the course of the inflammatory process and reduces the possibility of scar tissue formation.

Feature of action – significant inhibition of pituitary function and almost complete absence of MCS activity. Doses of 1-1.5 mg/day inhibit adrenal cortex, biological half-life (T1/2) is 32-72 hours (duration of inhibition of hypothalamic-pituitary-adrenal cortical layer system).

In terms 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.

Pharmacokinetics

Absorption

After oral administration is quickly and completely absorbed, the maximum concentration of dexamethasone in blood plasma is 1-2 hours. Distribution In blood plasma it is bound (60-70%) with specific carrier protein – transcortin. Crosses easily through histohematic barriers (including the blood-brain barrier and the placental barrier).

Metabolism

Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. Excretion Excreted by the kidneys (a small amount of dexamethasone penetrates into breast milk). The elimination half-life is 3-5 hours.

Indications

Endocrine system side: Replacement therapy of primary and secondary (pituitary) adrenal insufficiency, congenital adrenal hyperplasia, subacute thyroiditis and severe forms of post-radiotherapy thyroiditis. Rheumatic diseases:rheumatoid arthritis (including juvenile chronic arthritis) and extra-articular lesions in rheumatoid arthritis (lungs, heart, eyes, cutaneous vasculitis).

Systemic connective tissue diseases, vasculitis and amyloidosis (in combination therapy): Systemic lupus erythematosus (treatment of polyserositis and internal organ lesions), Sjögren’s syndrome (treatment of lung, kidney and brain lesions), systemic sclerosis (treatment of myositis, pericarditis and alveolitis), polymyositis, dermatomyositis, systemic vasculitis, amyloidosis (replacement therapy for adrenal insufficiency), scleroderma.

Skin diseases: pemphigoid, bullous dermatitis, herpetiform dermatitis, exfoliative dermatitis, erythema exudative (severe forms), erythema nodosa, seborrheic dermatitis (severe forms), psoriasis (severe forms), lichen, fungoid mycoses, Quincke’s edema, bronchial asthma, contact dermatitis, atopic dermatitis, serum disease, allergic rhinitis, drug disease (hypersensitivity to medications), urticaria after blood transfusions, systemic immune diseases (sarcoidosis, temporal arteritis).

Ocular diseases: proliferative changes in the orbit (endocrine ophthalmopathy, pseudotumors), sympathetic ophthalmia, immunosuppressive therapy in corneal transplantation.

Diseases of the gastrointestinal tract: ulcerative colitis (severe exacerbations), Crohn’s disease (severe exacerbations), chronic autoimmune hepatitis, rejection reaction after liver transplantation.

Blood diseases: Congenital or acquired acute pure aplastic anemia, autoimmune hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia, acute lymphoblastic leukemia (induction therapy), myelodysplastic syndrome, angioimmunoblastic malignant T-cell lymphoma (in combination with cytostatics), plastocytoma (in combination with cytostatics), anemia after myelofibrosis with myeloid metaplasia or lymphoplasmacytoid immunocytoma, systemic histiocytosis (systemic process).

Kidney diseases: Primary and secondary glomerulonephritis (Goodpasture syndrome), renal lesions in systemic connective tissue diseases (systemic lupus erythematosus, Sjögren’s syndrome), systemic vasculitis (usually in combination with cyclophosphamide), glomerulonephritis in polyarteritis nodosa, Churg-Strauss syndrome, granulomatosis Wegenerna purpura Schoenlein-Henoch mixed cryoglobulinemia, renal lesions in Takayasu arteritis, interstitial nephritis, immunosuppressive therapy after renal transplantation, induction of diuresis or reduction of proteinemia in idiopathic nephrotic syndrome (without uremia) and in renal lesions against systemic lupus erythematosus.

Malignant diseases: palliative therapy of leukemia and lymphoma in adults, acute leukemia in children, hypercalcemia in malignant neoplasms.

Other indications: tuberculous meningitis with subarachnoid block (in combination with adequate antituberculous therapy), trichinosis with neurological or myocardial manifestations.

Active ingredient

Composition

How to take, the dosage

The doses are set individually for each patient, depending on the nature of the disease, expected duration of treatment, tolerance of the drug and the patient’s response to the therapy.

The recommended starting dose for adults is 0.5 mg to 9 mg/day.

The usual maintenance dose is 0.5 mg to 3 mg/day.

The minimum effective daily dose is 0.5 to 1 mg.

The maximum daily dose is 10-15 mg.

The daily dose can be divided into 2 to 4 doses.

The dose is gradually reduced (usually by 0.5 mg every 3 days until a maintenance dose is reached) once the therapeutic effect is achieved.

In prolonged use of high oral doses, it is recommended that the drug be taken with meals, and antacids should be taken between meals. The duration of use of dexamethasone depends on the nature of the pathological process and the effectiveness of treatment and ranges from a few days to several months or more. Treatment is discontinued gradually (at the end some corticotropin injections are prescribed).

For the treatment of acute allergic diseases it is advisable to combine parenteral and oral administration: 1 day – 4-8 mg parenterally; 2 day – orally, 4 mg 3 times a day; 3, 4 day – orally, 4 mg 2 times a day; 5, 6 day – 4 mg/day, orally; 7 day – withdraw the drug.

Dosage in children

In children (depending on age) 2.5-10 mg/m2 body surface area/, dividing the daily dose into 3-4 doses.

Diagnostic tests for adrenal cortical hyperfunction

Short 1-mg dexamethasone test: 1 mg dexamethasone orally at 11 a.m.; blood draw for serum cortisol determination at 8 a.m. the next day.

Special 2-day test with 2 mg dexamethasone: 2 mg dexamethasone orally every 6 h for 2 days; daily urine collected to determine 17-hydroxycorticosteroid concentrations.

Interaction

Concomitant use of dexamethasone and nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of development and formation of gastrointestinal ulcers.

The effects of dexamethasone are diminished with concomitant use of CYPCA4 inducers (e.g., phenytoin, phenobarbitone, carbamazepine, primidone, rifabutin, rifampicin) or glucocorticoid metabolic clearance enhancers (ephedrine and aminoglutethimide); in these cases the dexamethasone dose should be increased.

The interaction between dexamethasone and the above drugs may distort dexamethasone suppression tests. If dexamethasone tests are to be performed during therapy with one of the listed drugs, this interaction must be considered when interpreting test results.

The concomitant use of dexamethasone and CYPCA4 isoenzyme inhibitors (e.g., ketoconazole, macrolide antibiotics) may lead to increased dexamethasone blood concentrations.

The concomitant use of drugs that are metabolized by CYPCA4 (e.g., indinavir, erythromycin) may increase their clearance, which may be accompanied by a decrease in their serum concentrations.

Dexamethasone decreases the effectiveness of hypoglycemic drugs, hypotensive agents, praziquantel and natriuretics (the dose of these drugs must be increased); increases the activity of heparin, albendazole and potassium-saving diuretics (if necessary, the dose of these drugs is reduced).

Dexamethasone may alter the effect of coumarin anticoagulants, so more frequent monitoring of prothrombin time is recommended during therapy. Antacids reduce absorption of dexamethasone in the stomach. Smoking has no effect on the pharmacokinetics of dexamethasone.

The concomitant use of oral contraceptives may increase the T1/2 of glucocorticosteroids, with a corresponding increase in their biological effects and increased incidence of adverse side effects.

The concomitant use of ritodrine and dexamethasone during labor is contraindicated because it can lead to maternal death due to pulmonary edema. Concomitant use of dexamethasone and thalidomide may cause toxic epidermal necrolysis.

Potential, therapeutically beneficial interactions: Concomitant use of dexamethasone and metoclopramide, diphenhydramine, prochlorperazine, or 5-HT3 receptor antagonists (serotonin or 5-hydroxytryptamine type 3 receptors) such as ondansetron or granisetron is effective in preventing nausea and vomiting caused by chemotherapy (cisplatin, cyclophosphamide, methotrexate, fluorouracil).

Special Instructions

When prescribing dexamethasone for intercurrent infections, septic conditions and tuberculosis, specific antibiotic therapy should be carried out simultaneously 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 disease and/or intestinal disease, osteoporosis.

Daily use develops atrophy of the adrenal cortex by 5 months of treatment.

May mask some symptoms of infections; immunizations are useless during treatment.

The abrupt withdrawal of GCS, especially if high doses have been previously used, results in GCS “withdrawal” syndrome (not due to hypocorticism): decreased appetite, nausea, lethargy, generalized muscular-skeletal pain, asthenia, and acute adrenal insufficiency may also occur (decreased 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, GCS are prescribed (as indicated) for the time. 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 the stress.

In children during long-term treatment it is necessary to monitor carefully the dynamics of growth and development. Children who have been in contact with patients with measles or chickenpox during treatment are given specific immunoglobulins prophylactically.

During treatment with dexamethasone (especially long-term) it is necessary to monitor the ophthalmologist, control blood pressure and water-electrolyte balance, as well as peripheral blood count and blood glucose concentration. In order to reduce side effects, anabolic steroids, antacids can be prescribed, and the intake of potassium ions can be increased (eating foods rich in potassium and calcium, or taking potassium, calcium, and vitamin D preparations). Foods should be rich in proteins, vitamins, and low in fat, carbohydrates, and salt.

In children during growth, GCS should be used only with absolute indications and under the special close supervision of the treating physician.

The use of dexamethasone carries a risk of severe anaphylactic reactions and bradycardia.

The therapy with the drug increases the risk of activation of strongyloidiasis.

Monitoring of patients with CHF, uncontrolled arterial hypertension, corneal trauma or ulcers, glaucoma is required during therapy.

The course of myasthenia gravis may worsen.

The use of GCS may cause changes in sperm motility.

The drug may mask symptoms of “peritoneal irritation” in patients with perforation of the stomach or intestinal wall.

The action of the drug is enhanced in patients with cirrhosis. It should be taken into account that dexamethasone clearance is decreased in patients with hypothyroidism and increased in patients with thyrotoxicosis.

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

With regard to possible side effects during therapy with Dexamethasone, caution should be exercised when driving vehicles and operating machinery and engaging in other activities requiring increased concentration and rapid psychomotor reaction.

Contraindications

The only contraindication for short-term use for “vital” indications is hypersensitivity to the active substance or excipients of the drug.

The drug is contraindicated in patients with galactosemia, lactase deficiency and glucose-galactose malabsorption syndrome, due to the fact that the drug contains lactose.

With caution.Parasitic and infectious diseases of viral, fungal or bacterial nature (current or recent, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), varicella, measles; Amoebiasis, strongyloidiasis (established or suspected); systemic mycosis; active and latent tuberculosis, the pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination, immunodeficiency conditions (including AIDS or HIV infection), and immunosuppression.including AIDS or HIV infection).

Gastrointestinal diseases: gastric and 12 duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with threat of perforation or abscess, diverticulitis.

Diseases of the cardiovascular system, including recent myocardial infarction (patients with acute and subacute myocardial infarction may have disseminated necrosis, delayed scar tissue formation and, therefore, cardiac muscle rupture), decompensated chronic heart failure, arterial hypertension, hyperlipidemia.

Endocrine diseases: diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Icenko-Cushing’s disease.

Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis; hypoalbuminemia and conditions predisposing to its occurrence; systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (III-IV stage), polio (except for bulbar encephalitis form), open and closed angle glaucoma, lactation period.

Side effects

Immune system disorders: infrequent hypersensitivity reactions, decreased immune response and increased susceptibility to infections.

Endocrine system disorders: frequent – transient adrenal insufficiency, growth retardation in children and adolescents, adrenal insufficiency and atrophy (decreased stress response), Icenko-Cushing’s syndrome, menstrual cycle disorders, hirsutism, transition of latent to clinically manifest diabetes, increased need for insulin or oral hypoglycemic medications in diabetic patients, sodium and water retention, increased potassium loss; very rare – hypokalemic alkalosis, negative nitrogen balance due to protein catabolism.

Mechanism and nutrition disorders: often – decreased carbohydrate tolerance, increased appetite and weight gain, obesity; rarely – hypertriglyceridemia.

Nervous system disorders: common – mental disorders; infrequent – optic papilloedema and increased intracranial pressure (pseudotumor cerebri) after discontinuation of therapy, dizziness, headache; very rare – convulsions, euphoria, insomnia, irritability, hyperkinesia, depression; rarely – psychosis.

Digestive system disorders: Infrequent – peptic ulcers, acute pancreatitis, nausea, hiccups, gastric or 12 duodenal ulcers; very rare – esophagitis, ulcer perforation and gastrointestinal bleeding (hematomeisis, melena), pancreatitis, gallbladder and intestinal perforations (especially in patients with chronic inflammatory diseases of the large intestine).

Senses: infrequent – posterior subcapsular cataract, increased intraocular pressure, tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes of cornea, exophthalmus.

Cardiovascular system: infrequent – arterial hypertension, hypertensive encephalopathy; very rarely – polyfocal ventricular extrasystoles, transient bradycardia, heart failure, myocardial infarction after recently suffered acute infarction.

Skin disorders: often – erythema, thinning and fragility of the skin, delayed wound healing, scarring, petechiae and ecchymosis, increased sweating, steroid acne, suppression of skin reaction during allergic tests; very rarely – angineurotic edema, allergic dermatitis, urticaria.

Musculoskeletal system disorders: frequent – muscle atrophy, osteoporosis, muscle weakness, steroid myopathy (muscle weakness due to catabolism of muscle tissue); infrequent – aseptic necrosis of bone; very rare – compression fractures of vertebrae, tendon ruptures (especially when some quinolones are used together), articular cartilage damage and bone necrosis (associated with frequent intraarticular injections).

Hematopoietic system disorders: rare – thromboembolic complications, decreased number of monocytes and/or lymphocytes, leukocytosis, eosinophilia (as in other glucocorticosteroids), thrombocytopenia and nonthrombocytopenic purpura.

Allergic reactions: rare – skin rash, pruritus, angioedema, bronchospasm, anaphylactic shock.

Urogenital system disorders: rarely – impotence.

Overdose

Single administration of a large number of tablets does not lead to clinically significant intoxication.

Symptoms: an increase in dose-dependent side effects is possible. In this case, the dose of the drug should be reduced.

Treatment: supportive and symptomatic.

There is no specific antidote.

Hemodialysis is ineffective.

Similarities