Description
Latin name
Dexamethasone
Pharmacological action
Dexamethasone is a synthetic glucocorticoid drug that contains a fluorine atom.
It has a pronounced anti-inflammatory, anti-allergic and desensitizing effect, has an immunosuppressive effectwill. Slightly retains sodium and water in the body. These effects are associated with inhibition of the release of inflammatory mediators by eosinophils by inducing the formation of lipocortins and a decrease in the number of mast cells producing hyaluronic acid with a decrease in capillary permeability by stabilization of cell membranes (especially lysosomal) and organelle membranes. The immunosuppressive effect is due to inhibition of the release of cytokinins (interleukin 1, 2, interferon gamma) from lymphocytes and macrophages. The main effect on metabolism is associated with protein catabolism, an increase in gluconeogenesis in the liver and a decrease in glucose utilization by peripheral tissues.
The drug inhibits the activity of vitamin D, which leads to a decrease in calcium absorption and an increase in its excretion. Dexamethasone inhibits the synthesis and secretion of ACTH and, secondly, the synthesis of endogenous glucocorticoids. A feature of the drug is a significant inhibition of pituitary function and a complete absence of mineralocorticoid activity.
Pharmacokinetics
Dexamethasone is rapidly and almost completely absorbed after oral administration. The bioavailability of dexamethasone tablets is approximately 80%. Cmax in plasma and the maximum effect after ingestion are achieved 1-2 hours after taking a single dose, the effect persists for about 2.75 days.
In plasma, approximately 77% of dexamethasone binds to proteins, primarily albumin. A small amount of dexamethasone binds to non-albumin proteins. Dexamethasone is a fat-soluble substance that can penetrate into extra- and intracellular spaces. In the central nervous system (hypothalamus, pituitary gland), its effects are due to binding to membrane receptors. In peripheral tissues, it binds to cytoplasmic receptors. Its decay occurs at the site of its action, i.e. in a cage. It is metabolized mainly in the liver to the formation of inactive metabolites. It is excreted by the kidneys.
Indications
From the endocrine system: replacement therapy of primary and secondary (pituitary) adrenal insufficiency, congenital adrenal hyperplasia, subacute thyroiditis and severe forms of post-radiation thyroiditis. Rheumatic diseases: rheumatoid arthritis (including juvenile chronic arthritis) and extra-articular lesions in rheumatoid arthritis (lungs, heart, eyes, skin vasculitis).
Systemic diseases of connective tissue, vasculitis and amyloidosis (as part of combination therapy): systemic lupus erythematosus (treatment of polyserositis and damage to internal organs), Sjogren’s syndrome (treatment of lung lesions, kidney and brain), systemic sclerosis (treatment of myositis, pericarditis and alveolitis), polymyositis, dermatomyositis, systemic vasculitis, amyloidosis (replacement therapy for adrenal insufficiency), scleroderma.
Diseases of the skin: pemphigoid, bullous dermatitis, herpetiform dermatitis, exfoliative dermatitis, exudative erythema (severe forms), nodular erythema, seborrheic dermatitis (severe forms), psoriasis (severe forms), lichen, fungoid mycosis, bronchitis mycosis, dermatitis, atopic dermatitis, serum sickness, allergic rhinitis, drug sickness (hypersensitivity to drugs), urticaria after blood transfusion, systemic immune diseases (sarcoidosis, temporal arteries um).
Eye diseases: proliferative changes in the orbit (endocrine ophthalmopathy, pseudotumors), sympathetic ophthalmia, immunosuppressive therapy for 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 lymphoma (T-cell), combination cell-medication combination with cytostatics), anemia after myelofibrosis with myeloid metaplasia or lymphoplasmacytoid immunocytoma, systemic histiocytosis (systemic process).
Kidney diseases: primary and secondary glomerulonephritis (Goodpasture syndrome), kidney damage in systemic connective tissue diseases (systemic lupus erythematosus, Sjogren’s syndrome), systemic vasculitis (usually in combination with cyclophosphamide), glomerulonephritis with polyarteritis nodosa, Charge-Strauss syndrome Wegener purpura of Shonlein-Genoch, mixed cryoglobulinemia, kidney damage in Takayasu arteritis, interstitial nephritis, immunosuppressive therapy after kidney transplantation, inducing diure and proteinemii or decrease in idiopathic nephrotic syndrome (without uremia) and renal lesions associated with 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 blockade (in combination with adequate anti-tuberculosis therapy), trichinosis with neurological or myocardial manifestations.
Contraindications
For short-term use according to “vital” indications, the only contraindication is hypersensitivity to the active substance or auxiliary components 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.
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), chicken pox, measles amebiasis, strongyloidosis (established or suspected) systemic mycosis active and latent tuberculosis, pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination ), lymphadenitis after BCG vaccination, immunodeficiency states (including AIDS or HIV infection).
Diseases of the gastrointestinal tract: peptic ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess, diverticulitis.
Diseases of the cardiovascular system, including recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the focus of necrosis is possible, slowing down the formation of scar tissue and, as a result, rupture of the heart muscle), decompensated chronic heart failure, 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 closed encephalomyelitis), lactation period.
Use during pregnancy and lactation
During pregnancy (especially in the first trimester), the drug can be used only when the expected therapeutic effect exceeds the potential risk to the fetus. With prolonged therapy during pregnancy, the possibility of impaired fetal growth is not ruled out. If used at the end of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn.
If treatment with the drug is necessary during breastfeeding, breast-feeding should be discontinued.
Special instructions
In patients requiring long-term therapy with dexamethasone, after discontinuation of therapy, a ² Ñwithdrawal ² Ñ syndrome may develop (also without clear signs of adrenal insufficiency): fever, nasal discharge, conjunctival hyperemia, headache, dizziness, drowsiness and irritability, muscle and joint pain, vomiting, weight loss, weakness, cramps . Therefore, dexamethasone must be discontinued by gradually reducing the dose. Rapid drug withdrawal can be fatal.
In patients receiving long-term therapy with dexamethasone and undergoing stress after its withdrawal, it is necessary to resume the use of dexamethasone due to the fact that the induced adrenal insufficiency can persist for several months after drug withdrawal.
Dexamethasone therapy may mask signs of existing or new infections and signs of bowel perforation in patients with ulcerative colitis. Dexamethasone can aggravate the course of systemic fungal infections, latent amoebiasis, or pulmonary tuberculosis.
Patients with acute pulmonary tuberculosis can be prescribed dexamethasone (together with anti-TB drugs) only in the case of a fulminant or severe disseminated process. Patients with inactive pulmonary tuberculosis receiving dexamethasone therapy or patients with positive tuberculin tests should receive antituberculous chemoprophylaxis in parallel.
Special attention and careful medical supervision is necessary for patients with osteoporosis, arterial hypertension, heart failure, tuberculosis, glaucoma, hepatic or renal failure, diabetes mellitus, active peptic ulcers, fresh intestinal anastomoses, ulcerative colitis and epilepsy. With caution, the drug is prescribed in the first weeks after acute myocardial infarction, patients with thromboembolism, with myasthenia gravis, glaucoma, hypothyroidism, psychosis or psychoneurosis, as well as patients over 65 years of age.
During dexamethasone therapy, decompensation of diabetes mellitus or latent to clinically manifest diabetes mellitus may occur.
With prolonged treatment, control of serum potassium levels is necessary.
Vaccination with live vaccines is contraindicated during dexamethasone therapy.
Immunization with killed viral or bacterial vaccines does not produce the expected specific titer increase in antibodies and therefore does not provide the necessary protective effect. Dexamethasone is usually not prescribed 8 weeks before vaccination and 2 weeks after vaccination.
Patients taking high doses of dexamethasone for a long time should avoid contact with measles patients if accidental contact occurs, prophylactic immunoglobulin treatment is recommended.
Caution must be exercised in treating patients who have recently undergone surgery or bone fracture, as dexamethasone can slow the healing of wounds and fractures.
The effects of glucocorticosteroids are enhanced in patients with cirrhosis or hypothyroidism.
Dexamethasone is used in children and adolescents only for strict indications. During treatment, strict monitoring of the growth and development of the child or adolescent is necessary.
Special information on some components of the
preparation Dexamethasone contains lactose, and therefore, it is contraindicated in patients with galactosemia, lactase deficiency and glucose-galactose malabsorption syndrome.
Influence on the ability to drive vehicles and other complex mechanisms
Dexamethasone does not affect the ability to drive vehicles and work with technical devices that require concentration and speed of psychomotor reactions.
Composition
1 tablet contains:
Active ingredient: dexamethasone 0.5 mg.
Side effects of the
From the immune system: infrequently – hypersensitivity reactions, decreased immune response and increased susceptibility to infections.
From the endocrine system: often – transient adrenal insufficiency, growth retardation in children and adolescents, insufficiency and atrophy of the adrenal glands (decrease in the response to stress), Itsenko-Cushing’s syndrome, menstrual irregularities, hirsuitism, the transition of latent diabetes mellitus to clinically manifest, increased need for insulin or oral hypoglycemic drugs in patients with diabetes mellitus, sodium and water retention , increased potassium loss is very rare – hypokalemic alkalosis, negative nitrogen balance due to protein catabolism.
Disorders of metabolism and nutrition: often – decreased carbohydrate tolerance, increased appetite and weight gain, obesity infrequently – hypertriglyceridemia.
From the nervous system: often – mental disorders infrequently – swelling of the papillae of the optic nerve and increased intracranial pressure (pseudotumor of the brain) after discontinuation of therapy, dizziness, headache is very rare – convulsions, euphoria, insomnia, irritability, hyperkinesia, depression rarely – psychosis. digestive system: infrequently – peptic ulcers, acute pancreatitis, nausea, hiccups, stomach or duodenal ulcers very rarely – esophagitis, perforation of ulcers and bleeding of the gastrointestinal tract (hematomesis, melena), pancreatitis, perforation of the gall bladder intestines (especially in patients with chronic inflammatory diseases of the large intestine).
From the sensory organs: infrequently – posterior subcapsular cataract, increased intraocular pressure, a tendency to develop secondary bacterial, fungal or viral infections of the eyes, trophic changes in the cornea, exophthalmos.
From the cardiovascular system: infrequently – arterial hypertension, hypertensive encephalopathy is very rare – polyfocal ventricular extrasystoles, transient bradycardia, heart failure, myocardial rupture after a recent acute heart attack.
On the part of the skin: often erythema, thinning and brittleness of the skin, delayed healing of wounds, striae, petechiae and ecchymosis, excessive sweating, steroid acne, suppression of the skin reaction during allergy tests, it is very rare – anginaedema, allergic dermatitis, urticaria.
From the musculoskeletal system: often – muscle atrophy, osteoporosis, muscle weakness, steroid myopathy (muscle weakness due to catabolism of muscle tissue) infrequently – aseptic necrosis of the bones very rarely – compression vertebral fractures, tendon ruptures (especially with the combined use of certain quinolones), damage to articular cartilage and bone necrosis (associated with frequent intraarticular injections).
From the hemopoietic system: rarely – thromboembolic complications, a decrease in the number of monocytes and / or lymphocytes, leukocytosis, eosinophilia (as in other glucocorticosteroids), thrombocytopenia and non-thrombocytopenic purpura.
Allergic reactions: rarely – skin rash, itching, angioedema, bronchospasm, anaphylactic shock.
From the genitourinary system: rarely – impotence.
Drug Interactions
The simultaneous use of dexamethasone and non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of developing and forming ulcers of the gastrointestinal tract.
The effect of dexamethasone decreases with the simultaneous use of inducers of the CYPZA4 isoenzyme (for example, phenytoin, phenobarbitone, carbamazepine, primidone, rifabutin, rifampicin) or drugs that increase the metabolic clearance of glucocorticoids (ephedrine and aminoglutethimide) in such cases it is necessary to increase the dose.
The interaction between dexamethasone and the above drugs can distort the results of dexamethasone suppression tests. If samples with dexamethasone should be performed during therapy with one of the listed drugs, this interaction should be taken into account when interpreting the results of the samples.
The simultaneous use of dexamethasone and inhibitors of the CYPZA4 isoenzyme (for example, ketoconazole, macrolide antibiotics) can lead to an increase in the concentration of dexamethasone in the blood.
The simultaneous use of drugs that are metabolized by CYPZA4 (for example, indinavir, erythromycin) can increase their clearance, which may be accompanied by a decrease in their serum concentrations.
Dexamethasone reduces the effectiveness of hypoglycemic drugs, antihypertensive drugs, praziquantel and natriuretics (it is necessary to increase the dose of these drugs) increases the activity of heparin, albendazole and potassium-sparing diuretics (if necessary, reduce the dose of these drugs).
Dexamethasone may alter the effect of coumarin anticoagulants, therefore, more frequent prothrombin time control is recommended during therapy. Antacids reduce the absorption of dexamethasone in the stomach. Smoking does not affect the pharmacokinetics of dexamethasone.
With the simultaneous use of oral contraceptives, T1 / 2 glucocorticosteroids may increase, with a corresponding increase in their biological effects and an increase in the frequency of adverse side effects.
The simultaneous use of ritodrin and dexamethasone during labor is contraindicated, as this can lead to the death of the mother due to pulmonary edema. The combined use of dexamethasone and thalidomide can cause toxic epidermal necrolysis.
Potential, therapeutically beneficial interactions: the simultaneous use of dexamethasone and metoclopramide, diphenhydramine, prochlorperazine or 5-HT3 receptor antagonists (serotonin or 5-hydroxytryptamine receptors of type 3), such as ondansetron or granisetron, is effective in the treatment of cirrhotic nausea , cyclophosphamide, methotrexate, fluorouracil).
Overdose
Single administration of a large number of tablets does not lead to clinically relevant intoxication.
Symptoms: Dose-related side effects may increase. In this case, the dose of the drug should be reduced.
Treatment: supportive and symptomatic.
There is no specific antidote.
Hemodialysis is ineffective.
Storage conditions
In a dark place at a temperature not exceeding 25 ° C.
Shelf life
5 years
Active ingredient
Dexamethasone
dosage form
tablets
Appointment
Appointment
Adults doctor’s prescription
OZ GNCLS, Russia
