Дексаметазон®

General characteristics. Structure:

Active ingredient: 4,37 mg of dexamethasone of sodium phosphate.

Excipients: Glitserol, dinatrium эдетат, sodium hydrophosphate a dihydrate, water for injections.

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

Pharmacological properties:

Pharmacodynamics. Dexamethasone - a synthetic adrenal hormone with glucocorticosteroid action (GKS). It has antiinflammatory and immunosuppressive effects, and also influences power metabolism, a homeostasis of glucose and (by means of negative feedback) secretion of the hypothalamic activating factor and adrenocorticotropic hormone of a hypophysis. GKS are fat-soluble substances and therefore easily get into target cells through cellular membranes. Linkng of hormone with a receptor causes conformational changes of a receptor and increases its affinity to DNA. The complex hormone receptor gets into a kernel of a cell and contacts the regulatory site of molecule DNA also known as an element of the glucocorticoid answer (GRE). The activated receptor contacts GRE or specific genes and regulates a transcription of template-RNA (MRNK). Again formed MRNK is transported to ribosomes which then participate in formation of new proteins. Depending on type of target cells and cellular processes formation of new proteins can how to amplify (for example, synthesis tyrosine-transaminase in liver cells), and to be suppressed (for example, synthesis of IL-2 in lymphocytes). As receptors to GKS are found in all fabrics, the realization of their action is enabled in the majority of cells of an organism.

Influence on metabolism of energy and homeostasis of glucose: dexamethasone, along with insulin, a glucagon and catecholamines, regulates accumulation and power consumption. It stimulates formation of glucose from pyruvate and amino acids in a liver and formation of a glycogen. In peripheral fabrics, in particular, in muscles, reduces consumption of glucose and will mobilize amino acids (from proteins) which are gluconeogenesis substrate in a liver. Direct effects on metabolism of fats are shown by the central redistribution of fatty tissue and strengthening of a lipolysis in response to influence of catecholamines.

Through receptors dexamethasone stimulates a renal blood stream and glomerular filtering in proximal tubules of kidneys, suppresses education and secretion of vasopressin and improves ability of kidneys to excrete acids. Increases sensitivity of vessels to pressor agents.

In high doses dexamethasone suppresses education by fibroblasts of collagen I and III of type and formation of glikozaminoglikan; due to oppression of formation of extracellular collagen and a matrix they slow down healing of wounds. Long reception of high doses causes the progressing resorption of a bone tissue as the mediated effect, and directly reduces its education (stimulates secretion of parathormone and suppresses secretion of a calcitonin). Besides, it results in negative balance of calcium - reduces absorption of calcium in intestines and strengthens its removal by kidneys. Usually it leads to a secondary hyperparathyreosis and a fosfaturiya.
Action of a pas hypothalamus and hypophysis: dexamethasone has more expressed effect, than endogenous cortisol by 30 times. Therefore it is more powerful inhibitor of secretion of the corticotropin-rileasing-factor (CR) and adrenocorticotropic hormone (AKTG). In pharmacological doses oppresses гипоталамо - pituitary and adrenal system, promotes development of secondary adrenal insufficiency. Insufficiency of bark of adrenal glands can develop for 5-7 day of administration of dexamethasone in the daily doses equivalent to 20 - 30 mg of Prednisonum or in 30 days of therapy by small doses. After cancellation of a short course of therapy (up to 5 days) high doses, function of bark of adrenal glands can be recovered in one week; after a long course normalization occurs later, usually this process borrows till 1 year. At some patients the irreversible atrophy of bark of adrenal glands can develop.

Antiinflammatory and immunosuppressive action of glucocorticosteroids is connected by both their molecular and biochemical effects. The molecular antiinflammatory effect is result of interaction of glucocorticosteroids with glucocorticoid receptors and changes of an expression of a number of the genes regulating formation of a set of the information molecules, proteins and enzymes which are taking part in process of an inflammation. It leads to decrease or the prevention of the fabric answer to an inflammation: oppression of cumulation of macrophages and leukocytes, suppression of phagocytosis and release of lizosomalny enzymes, synthesis of mediators of an inflammation, blocking of a macrophagic inhibitory factor. Dexamethasone reduces expansion and permeability of capillaries, reduces adhesion of leukocytes to an endothelium, synthesis of Pg, leukotrienes, thromboxanes oppresses. Dexamethasone reduces formation of leukotrienes by decrease in release of arachidonic acid of their cellular phospholipids that is result of suppression of activity of a phospholipase of A2. Action on a phospholipase is mediated by increase in concentration of a lipokortin (macrocortinum) which is A2 phospholipase inhibitor. Overwhelming effect of dexamethasone on synthesis of prostaglandins and thromboxane is result of decrease in synthesis of the specific MDNK coding formation of cyclooxygenase.

Dexamethasone warns or oppresses cellular immune responses of reaction of hypersensitivity of the slowed-down type), reduces quantity of T lymphocytes (T-helperov the I type), monocytes and eosinophils, linkng of immunoglobulins with their receptors, oppresses synthesis of interleykin: reduces the T-lymphocytic blastogenesis and reduces primary immune response. Activates humoral immunity due to stimulation T-helperov of the II type - strengthens development of antibodies. Significant effect is reduction of formation of a factor of a necrosis of a tumor (full name) and SILT-1.

Pharmacokinetics. Dexamethasone reaches the maximum concentration in a blood plasma in 5 minutes after intravenous administration (in/in) and in 1 h after intramuscular introduction (in/in). At local introduction to joints or soft tissues (in the defeat centers) absorption happens more slowly, than at use in oil. At in use action develops quickly; at use in oil the clinical effect develops in 8 h. Action is long: from 17 to 28 days after use in oil and from 3 days to 3 weeks after topical administration. Phosphate dexamethasone transition to dexamethasone in a blood plasma and synovial fluid happens quickly.

In a blood plasma about 77% of dexamethasone contacts proteins, it is preferential with albumine. Only the insignificant amount of dexamethasone contacts not albuminous proteins. Gets in out of - and intracellular spaces. In the central nervous system (a hypothalamus, a hypophysis) its effects are caused by linkng with membrane receptors. In peripheral fabrics contacts cytoplasmatic receptors. Disintegration happens in the place of its action, i.e., in a cell. It is metabolized preferential in a liver, and also in kidneys and other fabrics. It is removed preferential by kidneys. An elimination half-life (T1/2) - 190 min.

Indications to use:

Dexamethasone is applied intravenously or intramusculary in acute cases or at impossibility of performing peroral therapy.

• endocrine diseases: acute insufficiency of bark of adrenal glands, primary or secondary insufficiency of bark of adrenal glands, inborn hyperplasia of bark of adrenal glands, subacute thyroiditis;
• shock (burn, traumatic, operational, toxic) - at inefficiency of vasoconstrictors, plasma substituting drugs and other symptomatic therapy;
• brain hypostasis (brain tumors, craniocereberal injury, neurosurgical intervention, hematencephalon, encephalitis, meningitis, radiation injury)
• asthmatic status; heavy bronchospasm (exacerbation of bronchial asthma, chronic obstructive bronchitis);
• heavy allergic reactions, acute anaphylaxis;
• rheumatic diseases;
• general diseases of connecting fabric;
• acute heavy dermatosis;
• malignant diseases: palliative treatment of a leukosis and a lymphoma at adult patients; acute leukemia at children; a hypercalcemia at the patients having malignant tumors at impossibility of peroral treatment;
• blood diseases: acute hemolitic anemias, an agranulocytosis, an idiopathic Werlhof's disease at adults;
• serious infectious diseases (in combination with antibiotics);

Ophthalmology (subconjunctival, retrobulbar or parabulbar introduction): allergic conjunctivitis, a keratitis, a keratoconjunctivitis without damage of an epithelium, an iritis, an iridocyclitis, a blepharitis, blefarokonjyunktivit, a sclerite, an episcleritis, inflammatory process after injuries of an eye and operative measures, a sympathetic ophthalmia, immunosuppressive treatment after transplantation of a cornea;

-  local use (to the area of pathological education): keloids, diskoidny lupus erythematosus, ring-shaped granuloma.

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 glucocorticosteroids and reaction of the patient to the carried-out therapy.

Solution for injections can be entered intravenously (in the form of injections or infusions with solution of glucose or normal saline solution), intramusculary and locally (vnutrisustavno, into the centers of skin defeats, into soft tissues).

Parenteral use. Parenterally dexamethasone is entered in acute cases when performing peroral therapy is not possible and at the states described in the section "Indications to Use". The recommended average initial daily dose at in/in or use in oil varies from 0,5 mg to 9 mg and if it is necessary, up to 24 mg (it is equivalent 1/3-1/2 doses for intake). The initial dose of dexamethasone needs to be applied until the clinical effect is reached; then the dose gradually decreases to minimum effective. If high doses are applied within more than several days, the dose of drug has to decrease gradually for several next days or longer. Prolonged treatment has to be carried out in the dose which is not exceeding 0,5 mg/days.

Topical administration. The recommended single dose of dexamethasone for intra joint introduction makes from 0,4 mg to 4 mg. The dose depends on the size of the affected joint. The usual dose of dexamethasone makes from 2 mg to 4 mg for large joints and from 0,8 mg to 1 mg for small joints. Intra joint introduction can be repeated in 3-4 months. More frequent administration of dexamethasone can lead to injury of an intra joint cartilage and a necrosis of a bone. The usual dose of dexamethasone for introduction in a joint bag makes from 2 mg to 3 mg, for introduction to a sinew vagina - from 0,4 mg to 1 mg, and for sinews - from 1 mg to 2 mg. At introduction to the limited centers of defeats the same doses of dexamethasone, as for intra joint introduction are used. The drug can be administered at the same time, at most, in two centers. The recommended dexamethasone dose at an inflammation of soft tissues (periartikulyarny introduction) makes from 2 mg to 6 mg.

Use for children. At use in oil the dose for replacement therapy makes 0,02 mg/kg of body weight or 0,67 mg/sq.m of surface area of a body which divide into 3 injections at an interval of the 2nd day, or from 0,008 mg to 0,01 mg/kg of body weight or from 0,2 mg to 0,3mg/sq.m body surface areas daily. For other indications the recommended dose makes from 0,02 mg to 0,1 mg/kg of body weight or from 0,8 mg to 5 mg/sq.m of surface area of a body, each 12-24 h.

Urgent situations. The initial dose makes 4-20 mg which is repeated before achievement of necessary effect, the general daily dose seldom exceeds 80 mg. After achievement of therapeutic effect dexamethasone is entered on 2-4 mg as necessary with the subsequent gradual drug withdrawal. For maintenance of a long-term effect the drug is administered by each 3-4 h or in the form of long drop infusion. After stopping of acute conditions of the patient transfer to dexamethasone reception inside. At shock enter strictly in/in bolyusno in a dose of 2-6 mg/kg. If necessary repeated doses are entered by each 2-6 h or in the form of long into infusions in a dose of 3 mg/kg/days. Treatment by dexamethasone has to be carried out as a part of complex therapy of shock. Use of pharmacological doses is admissible only at life-threatening states, and, as a rule, this time does not exceed 48-72 h. At brain hypostasis the initial dose of 10 mg is entered in/in, then on 4 mg by each 6 h before stopping of symptomatology (usually during 12-24 h). After 2-4 days the dose is reduced and use of drug is gradually stopped within 5-7 days. The supporting treatment - on 2 mg in oil or by 2-3 times a day can be required by patients with malignant new growths.

At acute hypostasis of a brain carry out a short-term intensive care: the load dose for adults makes 50 mg in/in, then for 1-3 day each 2 h, for the 4th day - 4 mg each 2 h, for 5-8 day - on 4 mg each 4 h enter 8 mg, further lower a daily dose by 4 mg/days before its full cancellation. For children with body weight more than 35 kg the load dose makes 25 mg in/in, then for 1-3 day each 2 h, for the 4th day - 4 mg each 4 h, for 5-8 day - on 4 mg each 6 h enter 4 mg, further lower a daily dose by 2 mg/days before its full cancellation. To children with body weight less than 35 kg the load dose makes 20 mg in/in, then for 1-3 day each 3 h, for the 4th day - 4 mg each 6 h, for 5-8 day - on 2 mg each 6 h enter 4 mg, further lower a daily dose by 1 mg/days before full drug withdrawal.

At the acute self-limited allergic reactions or an exacerbation of chronic allergic diseases combine parenteral and oral administration of dexamethasone: the 1st day - in/in 4-8 mg, 2-3 day - in 1 mg 2 times a day, 4-5 day - in 0,5 mg 2 times a day, 6-7 day - in 0,5 mg once. For the 8th day estimate efficiency of therapy.

Features of use:

Dexamethasone solution should be applied to injections with care: system infections (against the background of adequate antimicrobic therapy), latent tuberculosis, a herpes infection of eyes (risk of perforation of a cornea), a diabetes mellitus, the chronic heart failure (CHF), recently postponed myocardial infarction, the chronic renal failure (CRF), a diverticulitis, arterial hypertension, a keratitis, epilepsy, ulcer colitis (at threat of perforation or infectious complications), recently established intestinal anastomosis, a round ulcer (including in the anamnesis), osteoporosis, gravis myasthenia, advanced age (the increased risk of development of osteoporosis and arterial hypertension), a hypothyroidism, a liver failure, a "steroid" myopathy, heavy affective frustration (including in the anamnesis, especially "steroid" psychosis), pregnancy, the breastfeeding period, children's age.

Against the background of parenteral therapy by glucocorticosteroids hypersensitivity reactions can develop (though it is rare). Therefore, before an initiation of treatment it is necessary to be careful (especially at patients with hypersensitivity to other medicines in the anamnesis). 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, decrease in body weight, weakness, spasms. Therefore, dexamethasone needs to be cancelled by gradual decrease in doses. Bystry drug withdrawal can be fatal to the patient.

If during use or during drug withdrawal the patient is exposed to the expressed stress (an injury, surgical intervention or a serious illness), a dose of dexamethasone it is necessary to increase or enter a hydrocortisone or a cortisone. 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 signs of infectious processes and signs of perforation of intestines.

Dexamethasone can aggravate the course of 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 in parallel therapy in antitubercular HP.

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 it is necessary to apply dexamethasone in the first weeks after an acute myocardial infarction, and also to patients with thromboembolisms, a myasthenia, glaucoma, a hypothyroidism, psychosis or psychoneuroses, and also to patients of advanced age.

During therapy by dexamethasone the decompensation of a diabetes mellitus or transition from latent to clinically manifest diabetes mellitus is possible.

At prolonged use control of level of potassium in blood serum is necessary.

During therapy by dexamethasone vaccination by live vaccines is 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 applied in 8 weeks prior to vaccination and within 2 weeks after vaccination.

Dexamethasone can raise a susceptibility or mask symptoms of infectious diseases. Chicken pox, measles, etc. infections can proceed more hard and even to lead to a lethal outcome at a neimma of vizirovanny persons. Immunosuppression develops at prolonged use of GKS more often, but can arise also at short-term treatment.

The patients accepting high doses of dexamethasone for a long time have to avoid contact with infectious patients; 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 interventions or fractures of bones as dexamethasone can slow down healing of wounds and changes.
Action of glucocorticosteroids amplifies at patients with cirrhosis or a hypothyroidism.

Intra joint use of glucocorticosteroids can be followed by local and system effects. Frequent use leads to destruction of a joint cartilage and a necrosis of a bone tissue.

Before intra joint introduction from a joint it is necessary to pump out and investigate (regarding existence of infectious process) synovial fluid. It is necessary to avoid introduction of glucocorticosteroids to the infected joint. If after an injection in a joint the septic inflammation develops, the corresponding antibioticotherapia is necessary.

Patients have to avoid load of a joint in which the injection, before full stopping of inflammatory process was made.

Injections in unstable joints are not recommended.

Glucocorticosteroids can change results of skin allergic tests.

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. Drug contains less than 1 mmol (23 mg) of sodium counting on one dose.

It is impossible to exclude a negative impact on a fruit and the newborn. Dexamethasone slows down pre-natal fetation. At pregnancy dexamethasone is applied only in individual, urgent cases if the expected advantage for mother justifies the existing risk for a fruit. At an eclampsia of pregnant women the smallest doses providing effective control of an associated disease are used. Glucocorticosteroids get through a placenta, and can reach high concentration in a fruit organism. Dexamethasone is less intensively metabolized in a placenta, in comparison, for example, with Prednisonum therefore at a fruit high concentration of dexamethasone can be defined. Therapeutic doses of glucocorticosteroids can increase risk of placental insufficiency, an oligogidramnion, growth inhibition and fetation and pre-natal death, increases in quantity of leukocytes (neutrophils) at the child, and also risk of development of adrenal insufficiency. There are no proofs of teratogenic action of glucocorticosteroids. If the woman during pregnancy received dexamethasone, in labor additional introduction 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.
A small amount of glucocorticosteroids cosecrete in breast milk. Therefore feeding is not recommended to mothers accepting dexamethasone by a breast, especially when using suprafiziologichesky doses (about 1 mg) as it can lead to a growth inhibition of the child and reduction of secretion of its endogenous corticosteroids.

Dexamethasone does not exert impact on ability to manage vehicles and     work  with  other  technical  devices  demanding the increased 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 system of a hemopoiesis: reduction  of quantity of monocytes  and/or lymphocytes, a leukocytosis, an eosinophilia, thrombocytopenia and not Werlhof's disease is rare. From an immune sistemy:nechasto allergic reactions (including hypersensitivity reactions), reduction of an immune response and increase in a susceptibility to infections; seldom: rash, bronchospasm, anaphylactoid reactions.

From a cardiovascular sistemy:nechasto: increase in the ABP; seldom: tromboembolic episodes;   very seldom:   polyfocal   ventricular   extrasystoles, passing bradycardia,  a thromboembolism,  a vasculitis,  decrease  in contractility of a myocardium, heart failure, a rupture of a myocardium after recently postponed acute heart attack.

From a nervous system: often: mental disturbances; infrequently: swelled nipples of an optic nerve and increase in intracranial pressure (a brain pseudoneoplasm) after therapy cancellation, dizziness, a headache, вертиго, neuropathy, changes of the personality and behavior, sleeplessness, irritability, hyperkinesias, a depression; seldom: psychoses; very seldom: spasms.

From endocrine system: often: adrenal insufficiency, pituitary insufficiency (especially against the background of a stress), an Icenco-Cushing syndrome, disturbances of a regularity of a menstrual cycle, a girsuitizm, suppression of growth at children, increase in body weight, obesity.

From a metabolism: often: decrease tolerance to glucose, "steroid" diabetes, a hyperglycemia, transition of a latent diabetes mellitus in clinically manifest, increase in need for insulin or peroral glucose-lowering drugs at patients with a diabetes mellitus, a delay of sodium and water, potassium loss strengthening; infrequently: gipertriglitseridemiya; very seldom: gipokaliyemichesky alkalosis, negative nitric balance.

From the alimentary system: infrequently: nausea, hiccups, stomach ulcer or 12-perstny gut; very seldom: 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 a musculoskeletal system: often: 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 skin pokrovov:chasto: the slowed-down healing of wounds, striya, petechias and ecchymomas, the increased perspiration, an acne, suppression of skin reaction when carrying out allergological tests, an erythema, thinning of skin, is very rare: Quincke's disease, allergic dermatitis, small tortoiseshell.

From sense bodys: infrequently: "steroid" cataract, glaucoma, increase in intraocular pressure; very seldom: exophthalmos, consecutive infections of eyes, retinopathy.

From a reproductive sistemy:redko: impotence.

Other: very seldom: swelled, hyper - or a hypoxanthopathy, an atrophy of skin or hypodermic fabrics, sterile abscesses and erubescence, burning sensation in the place of an injection, the arthropathy reminding Sharko's arthropathy.

Syndrome of "cancellation". If at the patient, it is long accepting glucocorticosteroids, quickly to reduce a drug dose, signs of adrenal insufficiency, arterial hypotension and death can develop. Also, development of the syndrome of "cancellation" which is not connected with adrenal insufficiency (anorexia, nausea, vomiting, a lethargy, a headache, fever, an arthralgia, epithelium desquamation, a mialgiya, decrease in body weight, decrease in the ABP) is possible.

In certain cases symptoms of a syndrome of "cancellation" can be similar to symptoms and signs of an aggravation or a recurrence of a disease concerning which the patient received treatment.

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

Interaction with other medicines:

Simultaneous use of dexamethasone and non-steroidal anti-inflammatory drugs increases risk of formation of ulcers in digestive tract. Effect of dexamethasone decreases at simultaneous use of inductors of CYP ZA4 enzyme (for example, Phenytoinum, Phenobarbitonum, carbamazepine, Primidonum, a rifabutin, rifampicin) or the drugs increasing metabolic clearance of glucocorticosteroids (ephedrine and aminoglutethimide); in such cases it is necessary to increase dexamethasone doses.

Interactions 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, then this interaction has to be considered at interpretation of results of tests.

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

Dexamethasone is the moderate inductor CYP ZA4. Simultaneous use of drugs which are metabolized by CYP ZA4 (индинавир, erythromycin) can increase their clearance that can be followed by decrease in their concentration in blood serum.

Due to suppression of activity of CYP ZA4 кетоконазол can increase plasma concentration of dexamethasone. On the other hand, кетоконазол can suppress synthesis of glucocorticosteroids in adrenal glands therefore, during decrease in doses of dexamethasone adrenal insufficiency can develop.

Dexamethasone reduces therapeutic action of hypoglycemic HP, anti-hypertensive means, a prazikvantel and natriuretics (it is necessary to increase doses of these drugs); increases activity of heparin, an albendazol and kaliysberegayushchy diuretics (in need of a dose of these drugs reduce).

Dexamethasone can change effect of coumarinic anticoagulants; therefore during therapy more frequent control of a prothrombin time is recommended. Simultaneous use of high doses of glucocorticosteroids with antagonists of beta2-adrenoceptors, thiazide diuretics, furosemide, Acidum etacrynicum, karboangidraza inhibitors, Amphotericinum increases risk of development of a hypopotassemia. At patients with a hypopotassemia aritmogenny and toxic effect of cardiac glycosides amplifies.

Antacids reduce absorption of dexamethasone in a stomach. Pharmacokinetic interaction of dexamethasone with food or alcohol was not studied; nevertheless, the simultaneous use of food and drugs with the high content of potassium is not recommended.

Smoking does not influence dexamethasone pharmacokinetics. Simultaneous use with cyclosporine increases risk of development of spasms in children. Glucocorticosteroids increase renal clearance of salicylates therefore it is sometimes difficult to achieve therapeutic concentration of salicylates in blood serum. It is necessary with care and to gradually reduce a dose of glucocorticosteroids as concentration of salicylates in blood serum and intoxication these drugs can increase.

At simultaneous use of oral contraceptives, anti-thyroid HP the elimination half-life 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 edematization of lungs.

Simultaneous use of dexamethasone and 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 for the purpose of the prevention of nausea and vomiting caused by chemotherapy (Cisplatinum, cyclophosphamide, a methotrexate, ftoruratsily).

Contraindications:

Hypersensitivity to active agent or auxiliary components of drug, acute viral, bacterial or system fungal infections (if the corresponding adequate therapy is not carried out), an Icenco-Cushing syndrome, vaccination by live vaccines; intramuscular introduction is contraindicated to patients with heavy disturbances of a hemostasis. For topical administration (in addition) - introduction to unstable joints, septic arthritis.

Overdose:

Symptoms: increase in the ABP, hypostases, round ulcer, hyperglycemia, consciousness disturbance.

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

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Solution for injections, 4 mg/ml. On 1 ml in ampoules of dark glass (type 1, Ph.Eur.) Apply the color point specifying the line of a fiasco of an ampoule and a color quoted ring on an ampoule. On 5 ampoules in the blister from PVC - aluminum foil. On 5 blisters together with the application instruction place in a pack from a cardboard.