Дексаметазон®

General characteristics. Structure:

Active ingredient: 0,5 mg of dexamethasone.

Excipient: lactoses monohydrate, starch corn, povidone, magnesium stearate, talc, silicon dioxide colloid, anhydrous.

The glucocorticosteroid drug possessing the antiinflammatory, antiallergic, desensibilizing, immunodepressive, antishock and anti-toxic effect increases sensitivity of beta adrenoceptors to endogenous catecholamines.

Pharmacological properties:

Pharmacodynamics. The glucocorticosteroid (GKS) - metilirovanny derivative a ftorprednizolona, slows down release interleykina-1 and interleykina-2, interferon scale from lymphocytes and macrophages. Renders the antiinflammatory, antiallergic, desensibilizing, antishock, anti-toxic and immunodepressive effect. Suppresses release by a hypophysis of adrenocorticotropic hormone (AKTG) and beta липотропина, but does not reduce the content of the circulating beta endorphine. Oppresses secretion of thyritropic hormone (TTG) and follicle-stimulating hormone (FSG). Increases excitability of the central nervous system (CNS), reduces quantity of lymphocytes and eosinophils, increases - erythrocytes (stimulates production of erythropoetins). Interacts with specific cytoplasmatic receptors, forms the complex getting into a cell kernel, stimulates synthesis of MRNK which induces formation of proteins, including a lipokortin which mediate cellular effects. Lipokortin oppresses A2 phospholipase, suppresses release of arachidonic acid and suppresses synthesis of endoperoxides, Pg, the leukotrienes promoting processes of an inflammation, an allergy, etc.

Protein metabolism: reduces amount of protein in plasma (at the expense of globulins) with increase in coefficient albumine/globulin, increases synthesis of albumine in a liver and kidneys; strengthens a protein catabolism in muscular tissue.

Lipidic exchange: increases synthesis of higher fatty acids and triglycerides (TG), redistributes fat (accumulation of fat is preferential in the field of a shoulder girdle, the person, a stomach), leads to development of a hypercholesterolemia.

Carbohydrate metabolism: increases absorption of carbohydrates from the digestive tract (DT); increases activity of the glyukozo-6-phosphatase leading to increase in intake of glucose from a liver in blood; increases activity of a fosfoenolpiruvatkarboksilaza and synthesis of the aminotransferases leading to activation of a gluconeogenesis.

Water and electrolytic exchange: Na + and water in an organism detains, stimulates removal of K+ (the ISS activity), reduces absorption of Sa2 + from a GIT, "washes away" Sa2 + from bones, increases removal of Sa2 + kidneys.

The antiinflammatory effect is connected with release oppression by eosinophils of mediators of an inflammation; induction of formation of a lipokortin and reduction of quantity of the mast cells producing hyaluronic acid; with reduction of permeability of capillaries; stabilization of cellular membranes and membranes of organellas (especially lizosomalny).

The antiallergic effect develops as a result of suppression of synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine, etc. biologically active agents, reduction of number of the circulating basophiles, suppression of development of adenoid and connecting tissue, decrease in number of T - and V-lymphocytes, mast cells, decrease in sensitivity of effector cells to mediators of an allergy, oppression of antibodyformation, change of an immune response of an organism.

At the chronic obstructive pulmonary disease (COPD) action is based mainly on braking of inflammatory processes, oppression of development or the prevention of hypostasis of mucous membranes, braking of eosinophilic infiltration of a submucosal layer of an epithelium of bronchial tubes, adjournment in a mucous membrane of bronchial tubes of the circulating cell-bound immune complexes, and also braking of an erozirovaniye and desquamation of a mucous membrane. Increases sensitivity of beta adrenoceptors of bronchial tubes of small and average caliber to endogenous catecholamines and exogenous sympathomimetics, reduces viscosity of slime due to oppression or reduction of its products.

Antishock and anti-toxic action is connected with increase in the arterial pressure (AP) (due to increase in concentration of the circulating catecholamines and recovery of sensitivity to them of adrenoceptors, and also vasoconstriction), decrease in permeability of a vascular wall, membranoprotektorny properties, activation of the enzymes of a liver participating in Endo's metabolism - and xenobiotics.

The immunodepressive effect is caused by braking of release of cytokines (interleykina1, interleykina2; interferon scale) from lymphocytes and macrophages.

Suppresses synthesis and secretion of AKTG, and for the second time - synthesis of endogenous GKS. Slows down connective tissue reactions during inflammatory process and reduces a possibility of formation of cicatricial fabric.

Feature of action - considerable inhibition of function of a hypophysis and almost total absence of the ISS of activity. Doses of 1-1.5 mg/days oppress bark of adrenal glands; biological T1/2 - 32-72 h (duration of oppression of system a hypothalamus-hypophysis-bast layer of adrenal glands).

On force of glucocorticosteroid activity of 0.5 mg of dexamethasone there correspond about 3.5 mg of Prednisonum (or Prednisolonum), 15 mg of a hydrocortisone or 17.5 mg of a cortisone.

Pharmacokinetics. Dexamethasone is quickly and almost completely soaked up after intake. Bioavailability of tablets of dexamethasone makes about 80%. The maximum concentration in a blood plasma and the maximum effect after intake are reached in 1 - 2 h; after reception of a single dose the effect remains within about 2,75 days. In a blood plasma about 77% of dexamethasone contacts proteins, it is preferential with albumine. The insignificant amount of dexamethasone contacts not albuminous proteins.

Dexamethasone - fat-soluble substance which can get in out of - and intracellular spaces. In TsNS (a hypothalamus, a hypophysis) its effects are caused by linkng with membrane receptors. In peripheral fabrics it contacts cytoplasmatic receptors. Its disintegration happens in the place of its action, i.e. in a cell. It is metabolized preferential in a liver before formation of inactive metabolites.

Indications to use:

From endocrine system: replacement therapy of primary and secondary (pituitary) adrenal insufficiency, inborn adrenal struma, subacute thyroiditis and severe forms of a postbeam thyroiditis. Rheumatic diseases: a pseudorheumatism (including juvenile chronic arthritis) and extraarticular defeats at a pseudorheumatism (lungs, heart, eyes, a skin vasculitis).

General diseases of connecting fabric, vasculites and amyloidosis (as a part of a combination therapy): a system lupus erythematosus (treatment of polyserosites and damages of internals), Shegren's syndrome (treatment of damages of lungs, kidneys and a brain), a system sclerosis (treatment of miozit, a pericardis and alveolitis), polymiosites, a dermatomyositis, system vasculites, an amyloidosis (replacement therapy at adrenal insufficiency), a scleroderma.

Skin diseases: pemphigoid, violent dermatitis, herpetiform dermatitis, exfoliative dermatitis, an exudative erythema (severe forms), a nodular erythema, seborrheal dermatitis (severe forms), psoriasis (severe forms), deprive, fungoidny mycoses, a Quincke's edema, bronchial asthma, contact dermatitis, atopic dermatitis, a serum disease, allergic rhinitis, a drug disease (hypersensitivity to medicines), a small tortoiseshell after hemotransfusion, general immune diseases (a sarcoidosis, temporal arteritis).

Diseases of eyes: proliferative changes in an orbit (an endocrine ophthalmopathy, pseudoneoplasms), a sympathetic ophthalmia, immunosuppressive therapy at transplantation of a cornea.

Digestive tract diseases: ulcer colitis (heavy aggravations), a disease Krone (heavy aggravations), chronic autoimmune hepatitis, reaction of rejection after transplantation of a liver.

Blood diseases: the inborn or acquired acute pure aplastic anemia, autoimmune hemolitic anemia, secondary thrombocytopenia at adults, an eritroblastopeniye, an acute lymphoblastoid leukosis (induction therapy), a miyelodisplastichesky syndrome, an angioimmunoblastny malignant T-cellular lymphoma (in a combination with cytostatics), a plastotsitoma (in a combination with cytostatics), anemia after a myelofibrosis with a myeloid metaplasia or lymphoplasmacytoid immunocytomes, a system histiocytosis (system process).

Diseases of kidneys: primary and secondary glomerulonephritis (Gudpascher's syndrome), damages of kidneys at general diseases of connecting fabric (a system lupus erythematosus, Shegren's syndrome), system vasculites (usually in combination with cyclophosphamide), a glomerulonephritis at a nodular polyarteritis, Charga-Shtrauss's syndrome, Wegener's granulomatosis of purple of Shonlyayna-Genokh, the mixed cryoglobulinemia, damages of kidneys at Takayasu's arteritis, intersticial nephrite, immunosuppressive therapy after transplantation of kidneys, induction of a diuresis or reduction of a proteinemia at an idiopathic nephrotic syndrome (without uraemia) and at damage of kidneys against the background of a system lupus erythematosus.

Malignant diseases: palliative therapy of leukemia and a lymphoma at adults, acute leukemia at children, a hypercalcemia at malignant new growths.

Other indications: tubercular meningitis with subarachnoidal blockade (in combination with adequate  antitubercular  therapy),  a trichinosis  with  neurologic or myocardial manifestations.

Route of administration and doses:

Doses are established individually for each patient, depending on the nature of a disease, the expected duration of treatment, portability of drug and reaction of the patient to the carried-out therapy.

The recommended initial dose for adults makes from 0,5 mg to 9 mg/days. A usual maintenance dose - from 0,5 mg to 3 mg/days. Minimum effective daily dose - 0,5-1 mg. The maximum daily dose - 10-15 mg. The daily dose can be divided into 2 - 4 receptions.

After achievement of therapeutic effect the dose is gradually reduced (usually by 0,5 mg each 3 days before achievement of a maintenance dose). At prolonged use of high doses inside, drug is recommended to be accepted during food, and in intervals between meals reception of antacids is necessary. Duration of use of dexamethasone depends on the nature of pathological process and efficiency of treatment and makes from several days to several months and more. Treatment is stopped gradually (at the end appoint several injections of corticotropin). At bronchial asthma, a pseudorheumatism, ulcer colitis of-1.5-3 mg/days; - at a system lupus erythematosus - 2-4.5 mg/days; - at oncohematological diseases - 7.5-10 mg. For  treatment  of acute  allergic  diseases  it is reasonable to combine parenteral and oral administration: 1 day - 4-8 mg parenterally; 2 day - inside, 4 mg 3 times a day; 3, 4 day - inside, 4 mg 2 times a day; 5, 6 day - 4 mg/days, inside; 7 day - drug withdrawal.

Dosing at children. To children   (      depending on   age)   appoint   2.5-10   mg/sq.m of surface area bodies/days, having divided a daily dose into 3-4 receptions. 

Diagnostic tests at hyperfunction of bark of adrenal glands. Short 1-mg dexamethasonal test: 1 mg of dexamethasone inside at 11:00; blood sampling for definition of cortisol of serum at 8:00 next day. The special 2-day test from 2 mg of dexamethasone: 2 mg of dexamethasone inside each 6 h within 2 days; daily urine for definition of concentration of 17 hydroxycorticosteroids gathers.

Features of use:

With care. Parasitic and infectious diseases of the virus, fungal or bacterial nature (now or recently postponed, including recent contact with the patient) - the herpes simplex surrounding herpes (a viremichesky phase), chicken pox, measles; the amebiasis, a strongyloidosis (established or suspected); system mycosis; active and latent tuberculosis, pre-and the postvaccinal period (8 weeks to and 2 weeks after vaccination), lymphadenitis after BTsZh inoculation, immunodeficiency (including AIDS or HIV infection).

Digestive tract diseases: a peptic ulcer of a stomach and a 12-perstny gut, an esophagitis, gastritis, an acute or latent round ulcer, recently created intestines anastomosis, ulcer colitis with threat of perforation or abscessing, a diverticulitis.

Diseases of cardiovascular system, including recently postponed myocardial infarction (at patients with an acute and subacute myocardial infarction distribution of the center of a necrosis, delay of formation of cicatricial fabric and thereof - a rupture of a cardiac muscle is possible), dekompensirovanny chronic heart failure, arterial hypertension, lipidemia.

Endocrine diseases - a diabetes mellitus (including disturbance of tolerance to carbohydrates), a thyrotoxicosis, a hypothyroidism, Itsenko-Cushing's disease.

Heavy chronic renal and/or liver failure, нефроуролитиаз; the hypoalbuminemia and states contributing to its emergence; system osteoporosis, gravis myasthenia, acute psychosis, obesity (the III-IV Art.), poliomyelitis (except for a form of bulbar encephalitis), open and closed-angle angle glaucoma, the lactation period.

Special instructions. At the patients needing long therapy by dexamethasone after the termination of therapy the syndrome of "cancellation" can develop (also without clear signs of adrenal insufficiency): fever, allocations from a nose, a conjunctiva hyperemia, a headache, dizziness, drowsiness and irritability, muscle and joints pain, vomiting, weight reduction, weakness, spasms. Therefore dexamethasone needs to be cancelled by a gradual dose decline. Bystry drug withdrawal can be fatal.

At the patients receiving long therapy by dexamethasone and who underwent a stress after its cancellation it is necessary to resume dexamethasone use because the induced adrenal insufficiency can remain within several months after drug withdrawal.

Therapy by dexamethasone can mask symptoms of the existing or new infections and signs of perforation of intestines at patients with ulcer colitis.

Dexamethasone can aggravate the course of system fungal infections, a latent amebiasis or a pulmonary tuberculosis.

Patients with an acute pulmonary tuberculosis can appoint dexamethasone (together with antitubercular drugs) only in case of the fulminantny or heavy disseminated process, the Patients with a healed tuberculosis of lungs receiving therapy by dexamethasone or patients with positive tuberkulinovy tests have to receive antitubercular chemoprophylaxis in parallel.

The special attention and careful medical observation is necessary for patients with osteoporosis, arterial hypertension, heart failure, tuberculosis, glaucoma, a liver or renal failure, a diabetes mellitus, active round ulcers, a fresh intestinal anastomosis, ulcer colitis and epilepsy.

With care drug is appointed in the first weeks after an acute myocardial infarction,  to patients with thromboembolisms,  with a myasthenia, glaucoma, a hypothyroidism, psychosis or psychoneuroses, and also to patients 65 years are more senior.

During therapy by dexamethasone the decompensation of a diabetes mellitus or transition latent in clinically manifest diabetes mellitus is possible. At prolonged treatment control of level of potassium in blood serum is necessary.

During therapy by dexamethasone vaccination by live vaccines are contraindicated. Immunization by the killed virus or bacterial vaccines does not give the expected growth of a caption of specific antibodies and therefore has no necessary protective action. Dexamethasone usually is not appointed in 8 weeks prior to vaccination and within 2 weeks after vaccination. The patients accepting high doses of dexamethasone for a long time have to avoid contact with patients with measles; at emergence of accidental contact preventive treatment is recommended by immunoglobulin.

It is necessary to be careful at treatment of the patients who recently transferred surgical intervention or a fracture of bones as dexamethasone can slow down healing of wounds and changes.

Action of glucocorticosteroids amplifies at patients with cirrhosis or a hypothyroidism.

Dexamethasone is applied at children and teenagers only according to strict indications. During treatment strict control of growth and development of the child or teenager is necessary.

Special information on some components of drug. Lactose in this connection, its use for patients with a galactosemia, deficit of lactase and a syndrome of glyukozo-galaktozny malabsorption is contraindicated is a part of the drug Dexamethasone.

During pregnancy (especially in the first trimester) the drug Dexamethasone can be used only when the expected medical effect exceeds potential risk for a fruit. At long therapy dexamethasone during pregnancy did not exclude a possibility of a growth disorder of a fruit. In case of use of the drug Dexamethasone in the last trimester of pregnancy there is a danger of emergence of an atrophy of bark of adrenal glands at a fruit that can demand performing replacement therapy from the newborn. If the woman during pregnancy received glyukortikosteroida, in the course of childbirth additional use of glucocorticosteroids is recommended. If patrimonial activity drags on or Cesarean section is planned, it is recommended to enter into the periportal period intravenously on 100 mg of a hydrocortisone each 8 h. In case of need therapies by the drug Dexamethasone breastfeeding should be stopped.

Dexamethasone does not exert impact on ability of control of motor transport and work with the technical devices demanding concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects (WHO):
very often> 1/10
often             from> 1/100 to <1/10
infrequently      from> 1/1000 to <1/100
seldom             from> 1/10000 to <1/1000
very seldom from <1/10000, including separate messages.
From immune system. - infrequently: hypersensitivity reactions, reduction of an immune response and increase in a susceptibility to infections.

From endocrine system. - it is frequent: tranzitorny adrenal insufficiency, delay of growth at children and teenagers, insufficiency and an atrophy of adrenal glands (reduction of response to a stress), an Icenco-Cushing syndrome, disturbance of a menstrual cycle, a girsuitizm, transition of a latent diabetes mellitus in clinically manifest, increase in need for insulin or peroral hypoglycemic medicines at patients with a diabetes mellitus, a delay of sodium and water, potassium loss strengthening; - it is very rare: a gipokaliyemichesky alkalosis, negative nitric balance owing to a catabolism of proteins.

Disturbances of metabolism and food. - it is frequent: decrease in tolerance to carbohydrates, increase in appetite and an increase of weight, obesity; - infrequently: gipertriglitseridemiya.

From a nervous system. - it is frequent: mental disorders; - infrequently: swelled nipples of an optic nerve and increase in intracranial pressure (a brain pseudoneoplasm) after therapy cancellation, dizziness, a headache, - is very rare; spasms, euphoria,   sleeplessness, irritability, hyperkinesia, depression; - it is rare: psychoses.

From the alimentary system. - infrequently: round ulcers, acute pancreatitis, nausea, a hiccups, stomach ulcers or a 12-perstny gut, - it is very rare: an esophagitis, perforation of an ulcer and bleeding of digestive tract (гематомезис, a melena), pancreatitis, perforation of a gall bladder and intestines (especially at patients with chronic inflammatory diseases of a large intestine).

From sense bodys. - infrequently: back subkapsulyarny cataract,  increase in intraocular pressure, tendency to development of consecutive bacterial, fungal or viral infections of eyes, trophic changes of a cornea, exophthalmos.

From cardiovascular system. - infrequently: arterial hypertension, hypertensive encephalopathy. - it is very rare: polyfocal ventricular extrasystoles, passing bradycardia, heart failure, a rupture of a myocardium after recently postponed acute heart attack.

From integuments. - it is frequent: an erythema, thinning and fragility of skin, the slowed-down healing of wounds, striya, petechias and ecchymomas, the increased perspiration, steroid eels, suppression of skin reaction when carrying out allergological tests, - is very rare: anginevroticheskiya swelled, allergic dermatitis, a small tortoiseshell.

From a musculoskeletal system. - it is frequent: an atrophy of muscles, osteoporosis, muscular weakness, a steroid myopathy (muscular weakness owing to a catabolism of muscular tissue); - infrequently: aseptic necrosis of bones; - very seldom; compression fractures of vertebras, ruptures of sinews (especially at combined use of some hinolon), injury of joint cartilages and necroses of bones (are connected with frequent intra joint injections).

From system of a hemopoiesis. - it is rare: tromboembolic episodes, reduction of quantity of monocytes and/or lymphocytes, a leukocytosis, an eosinophilia ( as well as at other glucocorticosteroids), thrombocytopenia and not Werlhof's disease.

Allergic reactions. - it is rare: skin rash, itch, Quincke's disease, bronchospasm, acute anaphylaxis.

From urinogenital system. - it is rare: impotence.

Signs and symptoms of a withdrawal of glucocorticosteroids. If at the patient, it is long accepting glucocorticosteroids, quickly to reduce a drug dose, can develop signs of adrenal insufficiency, arterial hypotension, death. In certain cases symptoms of cancellation can be similar to symptoms and signs of an aggravation or a recurrence of a disease concerning which the patient receives treatment.

At development of the heavy undesirable phenomena treatment by drug dexamethasone has to be stopped.

Interaction with other medicines:

Simultaneous use of dexamethasone and non-steroidal anti-inflammatory drugs (NPVP) increases risk of development and formation of ulcers of digestive tract. Effect of dexamethasone decreases at simultaneous use of inductors of an isoenzyme of CYP ZA4 (for example, Phenytoinum, Phenobarbitonum, carbamazepine, Primidonum, a rifabutin, rifampicin) or the drugs increasing metabolic clearance of glucocorticoids (ephedrine and aminoglutethimide); in such cases it is necessary to increase a dexamethasone dose. Interaction between dexamethasone and above-mentioned drugs can distort results of dexamethasonal supressionny tests. If tests with dexamethasone have to be carried out to therapy time by one of the listed drugs, this interaction has to be considered at interpretation of results of tests.

Simultaneous use of dexamethasone and inhibitors of an isoenzyme of CYP ZA4 (for example, кетоконазол, makrolidny antibiotics) can lead to increase in concentration of dexamethasone in blood.

Simultaneous use of drugs which are metabolized by CYP ZA4 (for example, индинавир, erythromycin) can increase their clearance that can be followed by decrease in their serumal concentration.

Dexamethasone reduces efficiency of hypoglycemic medicines, antihypertensives, a prazikvantel and natriuretics (it is necessary to increase a dose of these drugs); increases activity of heparin, an albendazol and kaliysberegayushchy diuretics (if necessary the dose of these drugs is reduced).

Dexamethasone can change effect of coumarinic anticoagulants therefore during therapy more frequent control of a prothrombin time is recommended. Antacids reduce absorption of dexamethasone in a stomach.
Smoking does not influence dexamethasone pharmacokinetics.

At simultaneous use of oral contraceptives T1/2 of glucocorticosteroids, with the corresponding strengthening of their biological effects and increase in frequency of adverse side effects can increase.

Contraindicated simultaneous use of Ritodrinum and dexamethasone during patrimonial activity as it can lead to death of mother because of a fluid lungs. Combined use of dexamethasone and a thalidomide can cause a toxic epidermal necrolysis.

Potential, therapeutic favorable interactions: simultaneous use of dexamethasone and Metoclopramidum, difengidramin, prochlorperazine or antagonists 5-NTZ receptors (serotoninovy or 5-gidroksitriptaminovy receptors 3 types), such as ондансетрон or гранисетрон, it is effective at prevention of nausea and vomiting, caused by chemotherapy (Cisplatinum, cyclophosphamide, a methotrexate, ftoruratsily).

Contraindications:

For short-term use according to "vital" indications the only contraindication is hypersensitivity to active agent or auxiliary components of drug. The drug Dexamethasone is contraindicated to patients with a galactosemia, deficit of lactase and a syndrome of glyukozo-galaktozny malabsorption because lactose is a part of drug.  

Overdose:

Single use of a large number of tablets does not lead to clinically significant intoxication. Symptoms: strengthening of dozozavisimy side effects is possible. In this case the dose of drug should be reduced.

Treatment: supporting and symptomatic. The specific antidote does not exist. The hemodialysis is inefficient.

Storage conditions:

At a temperature not above 25 °C, in original packaging. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 0,5 mg. On 10 tablets in the blister. On 1 blister together with the application instruction in a pack cardboard, or on 10 tablets in a bottle of dark glass (type Sh) with a plastic cover from polyethylene. The free space in a bottle is filled with cotton wool. On 1 bottle together with the application instruction in a pack cardboard.