Dexamethasone - instructions for use, dose, side effects, contraindications

Synthetic glucocorticosteroid (GCS) - methylated derivative of fluoride prednisolone. Has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, anti-shock and antitoxic action, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

It interacts with cytoplasmic receptors of glucocorticosteroids (GCS) (receptors for GCS are present in all tissues, especially in the liver), with the formation of a complex inducing the formation of proteins (including enzymes that regulate vital processes in cells.)

Protein metabolism: reduces the number of globulins in the plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin / globulin ratio in blood plasma); reduces synthesis and enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (mobilization from the subcutaneous tissue of the extremities and accumulation of fat mainly in the region of 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 (increased intake of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: detains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticoid activity), reduces the absorption of calcium ions from the gastrointestinal tract, causes the calcium to "wash out" of the bones and increases its renal excretion, and reduces the mineralization of bone tissue.

Anti-inflammatory effect is associated with the suppression of the release of eosinophils and mast cells by inflammatory mediators; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in the permeability of capillaries; stabilization of cell membranes (especially lysosomal) and membranes of organelles. It works on all stages of the inflammatory process: it inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin oppresses phospholipase A₂, suppresses the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, promoting inflammation processes, allergies, etc.), the synthesis of "pro-inflammatory cytokines" (interleukin-1, tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.

Immunodepressive effect is caused by involution of lymphoid tissue, suppression of lymphocyte proliferation (especially T-lymphocytes), suppression of B-lymphocyte migration and interaction of T and B lymphocytes, inhibition of release of cytokines (interleukin-1,2, gamma-interferon) from lymphocytes and macrophages and a decrease the formation of antibodies.

Antiallergic effect develops as a result of a decrease in the synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils of histamine and other biologically active substances, a decrease in the number of circulating basophils, suppression of lymphoid and connective tissue development, a decrease in the number of T- and B-lymphocytes, decrease of sensitivity of effector cells to mediators of allergy, inhibition of antibody formation, changes in the immune response of the organism.

In obstructive airway diseases, the effect is mainly due to inhibition of inflammatory processes, prevention or reduction of mucosal edema, a decrease in the eosinophilic infiltration of the submucosal layer of the bronchial epithelium and the deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucosa. Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchial tubes to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.

Suppresses the synthesis and secretion of adrenocorticotropic hormone and secondarily - the synthesis of endogenous GCS.

The peculiarity of the action is a significant inhibition of the pituitary function and a virtually complete absence of mineralocorticosteroid activity.

Doses of 1-1.5 mg / day inhibit the function of the adrenal cortex; the biological half-life is 32-72 hours (the duration of oppression of the hypothalamic-pituitary-cortical adrenal gland system).

The strength of the glucocorticoid activity of 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:

ATSucks: after intake quickly and completely absorbed. The maximum concentration in the blood is reached in 1-2 hours.

RAssignment: in the blood binds (60-70%) to a specific carrier protein - transcortin. Easily passes through the histohematological barriers (including through blood-brain and placental).

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

ATIntroduction: is excreted by the kidneys (a small part - lactating glands).The half-life is 3-5 hours.

Indications:

Primary and secondary adrenal insufficiency (usually in combination with mineralocorticoids); congenital hyperplasia of the adrenal cortex; subacute thyroiditis; hypercalcemia in malignant neoplasms; bronchial asthma; systemic connective tissue diseases (rheumatoid arthritis in the exacerbation phase, systemic lupus erythematosus, scleroderma, etc.); skin diseases (psoriasis, eczema, dermatitis, pemphigus, acute erythroderma, etc.); ulcerative colitis; diseases of the hematopoiesis: agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital (erythroid) hypoplastic anemia; cerebral edema (usually after a previous parenteral administration of a glucocorticosteroid); Conducting a test in the differential diagnosis of hyperplasia (hyperfunction) and adrenal cortex tumors.

Contraindications:

Hereditary intolerance to galactose, lactase deficiency or glucose-galactose malabsorption, hypersensitivity to dexamethasone or components of the drug.

Carefully:

The drug should be prescribed in the following diseases and conditions: gastrointestinal tract diseases (peptic ulcer of stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis); parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a patient: herpes simplex, viremic phase of herpes zoster, chicken pox, measles, amebiasis, strongyloidiasis, systemic mycosis, active or 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 cardiovascular system, incl. recently suffered myocardial infarction (in patients with acute and subacute myocardial infarctionpossible spread of the foci of necrosis, slowing the formation of scar tissue and as a result - rupture of the heart muscle), decompensated chronic heart failure, hypertension, hyperlipidemia; endocrine diseases: diabetes mellitus (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV c); severe chronic renal and / or hepatic insufficiency, nephrourolythiasis; hypoalbuminemia and conditions predisposing to its occurrence (cirrhosis of the liver, nephrotic syndrome); systemic osteoporosis, myasthenia gravis gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma, pregnancy. Application in severe infectious diseases is possible only against the background of specific antimicrobial therapy.

In children during the growth period, SCS should be used only in absolute indications and under the strictest supervision of the attending physician.

Pregnancy and lactation:

In The time of pregnancy (especially in the first trimester) the drug can be used only for vital indications.During pregnancy, the drug is used only if the potential benefit to the mother exceeds the potential risk to the fetus. With prolonged therapy during pregnancy, the possibility of impaired fetal growth is not ruled out. In the case of use in the III 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 breastfeeding should be discontinued.

Dosing and Administration:

The dosage regimen is individual and depends on the indications, the severity of the disease and the patient's reaction to therapy.

Dexamethasone is prescribed inside during or after a meal, once in the morning (a small dose) or in 2-3 doses (a large dose). The average daily intake for adults ranges from 2-3 mg to 6 mg. The maximum daily dose is 10-15 mg.

After reaching the therapeutic effect, the dose is gradually reduced (usually by 0.5 mg in 3 days) to the maintenance dose - 2-4.5 and more mg / day. The maximum effective dose is 0.5-1 mg / day.

Children prescribe 0,0833-0,3333 mg / kg or 0,0025-0,0001 mg / m² per day in 3-4 hours depending on the age.

The duration of the use of Dexamethasone depends on the nature of the pathological process and the effectiveness of the treatment and ranges from several days to several months or more. Treatment is stopped gradually.

Side effects:

Usually Dexamethasone well tolerated. It has a low mineralocorticoid activity, i.e. its effect on water-electrolyte exchange is small. As a rule, low and medium doses of Dexamethasone do not cause delays in sodium and water in the body, increased excretion of potassium.

The following side effects are described:

From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, oppression of the adrenal gland function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased arterial pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delay sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, impaired digestion,flatulence, hiccough. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the side of the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. 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.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the sense organs: 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 eyes, trophic changes in the cornea, exophthalmos.

From the side of metabolism: increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

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

From the musculoskeletal system: slowing the growth and processes of ossification in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and thigh bone), rupture of muscle tendons, steroid myopathy, muscle loss (atrophy).

From the skin and mucous membranesto: delayed healing of wounds, petechiae, ecchymosis, thinning of the skin, hyper- or hypopigmentation, acne, striae, propensity to develop pyoderma and candidiasis.

Allergic reactions: skin rash, itching, anaphylactic shock.

Other: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

If any of the side effects listed in the instruction are aggravated, or you notice any other side effects not listed in the instructions, inform the doctor about it.

Overdose:

It is possible to increase dose-dependent side effects. It is necessary to reduce the dose of Dexamethasone. Treatment is symptomatic.

Interaction:

Pharmacokinetic:

Concurrent use of dexamethasone with:

- inducers of microsomal liver enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) leads to a decrease in its concentration;

- acetylsalicylic acid - to accelerate its elimination and decrease in blood concentration (with dexamethasone withdrawal, the level of salicylates in the blood increases and the risk of side effects increases);

- prazikvantelom - to reduce its concentration in the blood;

- cyclosporine and ketoconazole - to slow the metabolism of dexamethasone, which can in some cases lead to an increase in its toxicity;

- estrogens and oral estrogen-containing contraceptives - to reduce the clearance of dexamethasone, which may be accompanied by an increase in the severity of its action;

- antacids - to reduce the absorption of dexamethasone;

- antithyroid drugs - to reduce the clearance of dexamethasone;

- thyroid hormones - to increase the clearance of dexamethasone;

Pharmacodynamic:

Concurrent use of dexamethasone with:

- diuretics (especially thiazide "and carbonic anhydrase inhibitors) may lead to increased excretion of potassium ions;

- with sodium-containing drugs - to develop edema and increase blood pressure;

- amphotericin B - to enhance the excretion of potassium ions from the body and increase the risk of developing heart failure;

- cardiac glycosides - worsen their tolerability and increased likelihood of ventricular arrhythmias (due to induced hypokalemia);

- indirect anticoagulants - to weakening (less often to strengthen) their actions (dose adjustment is required);

- anticoagulants and thrombolytics - increase the risk of bleeding from ulcers in the gastrointestinal tract;

- ethanol and nonsteroidal anti-inflammatory drugs (NSAIDs) - to increased risk of erosive-ulcerous lesions in the gastrointestinal tract and of bleeding (in combination with NSAIDs for the treatment of arthritis may be reduced dose glucocorticosteroids for therapeutic effect summation);

- paracetamol - to increase the risk of hepatotoxicity (induction of hepatic enzymes and the formation of a toxic metabolite of paracetamol);

- insulin and oral hypoglycemic drugs, hypotensive drugs - to reduce their effectiveness;

- vitamin D - to reduce its effect on the absorption of calcium ions in the intestine;

- somatotropin - to reduce the effectiveness of the latter;

- M-holinoblokatorami (including antihistamines and tricyclic antidepressants) and nitrates - to increased intraocular pressure;

- isoniazid and mexelitin - to the activation of their metabolism (especially in "slow" acetylators), which leads to a decrease in their plasma concentrations;

- inhibitors of carbonic anhydrase and "loop" diuretics - to an increased risk of osteoporosis;

- indomethacin - to an increased risk of developing its side effects due to crowding out dexamethasone from association with albumins;

- adrenocorticotropic hormone - to enhance the action of dexamethasone;

- ergocalciferol and parathyroid hormone - to slow the development of osteopathy caused by dexamethasone;

- androgens and steroid anabolic drugs - to the development of peripheral edema and hirsutism, the appearance of acne;

- mitotane and other inhibitors of the function of the adrenal cortex - to the possible need to increase the dose of dexamethasone;

- living antiviral vaccines and against other types of immunizations - to increase the risk of virus activation and the development of infections;

- antipsychotic drugs (antipsychotics) and azathioprine - to increase the risk of developing cataract with the appointment of dexamethasone.

Special instructions:

Before starting treatment, the patient should be examined for possible contraindications. Clinical examination should include examination of the cardiovascular system, radiology examination of the lungs, examination of the stomach and duodenum, urinary system, vision organs; the control of the formula of blood, the content of glucose and electrolytes in the blood plasma.

During treatment with Dexamethasone (especially prolonged), it is necessary to observe the oculist, control blood pressure and the state of water electrolyte balance, as well as patterns of peripheral blood and blood glucose levels.

In order to reduce side effects, antacids can be prescribed, as well as increased intake of K⁺ in the body (diet, potassium preparations). Food should be rich in proteins, vitamins, with a restriction of fat, carbohydrates and table salt.

The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis.

The drug may enhance existing emotional instability or psychotic disorders. When referring to a psychosis in an anamnesis Dexamethasone in high doses prescribed under the strict supervision of a doctor.

In stressful situations during maintenance treatment (for example, surgical operations, trauma or infectious diseases), a correction of the dose of the drug should be made in connection with an increase in the need for glucocorticosteroids.

With daily administration to 5 months of treatment, atrophy of the adrenal cortex develops. It is necessary to carefully monitor the patient within a year after the end of long-term therapy with Dexamethasone in connection with the possible development of a relative deficiency of the adrenal cortex. If during this period there are stressful situations, prescribe (according to indications) for the time of GCS, if necessary in combination with mineralocorticoids.

In case of sudden cancellation, especially in case of prior application of high doses, it is possible to develop the "withdrawal" syndrome (anorexia, nausea, block, generalized musculoskeletal pain, general weakness), as well as an exacerbation of the disease for which it was prescribed Dexamethasone.

During treatment, Dexamethasone should not be vaccinated due to a decrease in its effectiveness (immune response).

Assigning Dexamethasone with intercurrent infections, septic states and tuberculosis, it is necessary to simultaneously perform antibiotic treatment of bactericidal action.

Dexamethasone can mask certain symptoms of infections.

Children during long-term treatment with Dexamethasone need careful monitoring of the dynamics of growth and development. Children who were in contact with sick measles or chickenpox during the treatment period prophylactically prescribe specific immunoglobulins.

Patients with diabetes should monitor blood glucose and, if necessary, correct therapy.

An x-ray control of the osteoarticular system (images of the spine, hands) is shown.

In patients with latent infectious diseases of the kidneys and urinary tract Dexamethasone can cause leukocyturia, which can have diagnostic value.

Dexamethasone increases the metabolites content of 11- and 17-oxyketocorticosteroids.

Effect on the ability to drive transp. cf. and fur:

It should be noted that the drug can cause a number of side effects from the nervous system (dizziness, etc.), which can slow down the reaction rate.

Form release / dosage:

Tablets, 0.5 mg.

Packaging:

50 tablets in a polymer canister are placed together with instructions for use in a pack of cardboard.

For 10 tablets in a planar cell package. 1, 2 or 5 contour squares are placed together with the instructions for use in a pack of cardboard.

Storage conditions:

Store in a dry, protected from light and out of reach of children, at a temperature of 15 to 25 ° C.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016061 / 01

Date of registration:24.09.2009 / 01.02.2013

Expiration Date:Unlimited

The owner of the registration certificate:EXPERIMENTAL FACTORY ГНЦЛС, ООО EXPERIMENTAL FACTORY ГНЦЛС, ООО Ukraine

Manufacturer: & nbsp

EXPERIMENTAL FACTORY ГНЦЛС, ООО Ukraine

Information update date: & nbsp21.03.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)