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

Excipients: glycerol (glycerol) - 22.5 mg, sodium hydrophosphate dodecahydrate (sodium phosphate disubstituted 12-water) - 0.8 mg, disodium edetate dihydrate (disodium ethylenediaminetetraacetic acid, trilon B) 0.1 mg_,water for injection - up to 1 ml.

Description:Transparent or slightly opalescent, colorless or slightly colored liquid.

Pharmacotherapeutic group:Glucocorticosteroid

ATX: & nbsp

H.02.A.B.02 Dexamethasone

S.01.B.A.01 Dexamethasone

H.02.A.B Glucocorticoids

S.01.B.A Corticosteroids

Pharmacodynamics:

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.

Interacts with specific cytoplasmic receptors (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).

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 (Lipokortin inhibits phospholipase A2 suppresses liberatiou arachidonic acid inhibits the biosynthesis endoperekisey, leukotrienes contribute inflammation, allergies, etc.), synthesis of "proinflammatory cytokine" (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-cell 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 decreased synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils, histamine, and others. bioactive substances, reducing the number of circulating basophils, suppression of lymphoid and connective tissues, reduce the number of T and B lymphocytes, mast cells, reducing the sensitivity of the effector cells to the mediators of allergy, inhibition of antibody production, changes in the immune response.

When obstructive airway diseases action is caused mainly by the inhibition of inflammatory processes, prevention or reduction of severity of mucosal edema, reduction of eosinophil infiltration bronchial epithelium submucosal layer and deposition in the bronchial mucosa of circulating immune complexes and erozirovaniya inhibition and mucosal desquamation.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. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

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

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

A feature of the action is a significant inhibition of the pituitary function and a virtually complete absence of mineralocorticoid activity.

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

By the force of glucocorticoid activity 0.5 mg dexamethasone correspond to about 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone or cortisone 17.5 mg.

Pharmacokinetics:

Blood is bound (60-70%) with a specific transporter protein - transcortin. Easily passes through the histohematological barriers (including through blood-brain and placental). Metabolised in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites. It is excreted by the kidneys (a small part by the lactating glands).The half-life of dexamethasone from the plasma is 3-5 hours.

Indications:

Diseases requiring the introduction of a fast-acting glucocorticosteroid, as well as cases where oral administration of the drug is not possible:

- Endocrine diseases: acute insufficiency of the adrenal cortex, primary or secondary insufficiency of the adrenal cortex, congenital hyperplasia of the adrenal cortex, subacute thyroiditis;

- shock (burn, traumatic, operational, toxic) - with ineffectiveness of vasoconstrictors, plasma-substituting drugs and other symptomatic therapy;

- edema of the brain (with a brain tumor, craniocerebral trauma, neurosurgical intervention, cerebral hemorrhage, encephalitis, meningitis, radiation injury);

- asthmatic status; severe bronchospasm (exacerbation of bronchial asthma);

- severe allergic reactions, anaphylactic shock;

- rheumatic diseases;

- systemic connective tissue diseases;

- Acute severe dermatoses;

- malignant diseases: palliative treatment of leukemia and lymphoma in adult patients; acute leukemia in children; hypercalcemia in patients with malignant tumors, with the impossibility of oral treatment;

- Blood diseases: acute hemolytic anemia, agranulocytosis, idiopathic thrombocytopenic purpura in adults;

- in ophthalmic practice (subconjunctival, retrobulbar or parabulbar injection): allergic conjunctivitis, keratitis, keratoconjunctivitis without epithelial damage, irit, iridocyclitis, blepharitis, blepharoconjunctivitis, scleritis, episcleritis, inflammatory process after eye injuries and surgical interventions, sympathetic ophthalmia, immunosuppressive treatment after corneal transplantation;

- local application (in the area of pathological education): keloids, discoid lupus erythematosus, annular granuloma.

Contraindications:

The only contraindication for short-term use for life indications is hypersensitivity to dexamethasone or the components of the drug.

Carefully:

With the following diseases and conditions:

- Diseases of the gastrointestinal tract - gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing threat, diverticulitis.

- Parasitic and infectious diseases of viral, fungal or bacterial nature (currently occurring or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidiasis; systemic mycosis; active and latent tuberculosis. The use in severe infectious diseases is permissible only against the background of specific therapy.

- 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 infarction, the spread of the necrosis foci, slowing the formation of scar tissue and as a result - rupture of the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia.

- Endocrine diseases - diabetes (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.

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:

During pregnancy (especially in the first trimester) the drug can be applied only when the expected therapeutic effect for 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 case of application 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 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 patient's condition and his reaction to therapy.

The drug is administered intravenously slowly by jet or drip (in acute and urgent conditions); intramuscularly; possibly also local (in pathological education) introduction.

To prepare a solution for intravenous drip infusion, an isotonic solution of sodium chloride should be used or 5% solution of dextrose.

In an acute period with various diseases and at the beginning of therapy Dexamethasone used in higher doses. During the day, you can inject 4 to 20 mg of Dexamethasone 3-4 times.

Doses of the drug for children (intramuscularly):

The dose of the drug during replacement therapy (with adrenal cortex deficiency) is 0.0233 mg / kg body weight or 0.67 mg / m² body surface area divided into 3 doses, every 3rd day or 0.00776-0.01165 mg / kg body weight or 0.233-0.335 mg / m² body surface area daily.

With other indications, the recommended dose is from 0.02776 to 0.1666 mg / kg body weight or 0.833 to 5 mg / m² body surface area 12-24 hours.

When the effect is achieved, the dose is reduced to a maintenance dose or until the treatment is discontinued.The duration of parenteral use is usually 3-4 days, then switch to maintenance therapy with dexamethasone in tablets.

Long-term use of high doses of the drug requires a gradual dose reduction in order to prevent the development of acute adrenocortical insufficiency.

Side effects:

Possible side effects when using the drug are presented below in accordance with the frequency of occurrence: often (≥ 1/100, < 1/10), infrequently (≥ 1/1000, < 1/100), rarely (≥ 1/10000, < 1/1000), rarely (< 1/10000), including individual messages.

Disorders from the hematopoiesis system:

rarely - a decrease in the number of monocytes and / or lymphocytes, leukocytosis, eosinopenia, thrombocytopenia and netrombotsitopenicheskaya purpura.

Immune system disorders:

infrequently - allergic reactions (including hypersensitivity reactions), decreased immune response and increased susceptibility to infections;

rarely - rash, bronchospasm, anaphylactoid reactions.

Heart Disease:

very rarely - polyfocal ventricular extrasystoles, transient bradycardia, decreased myocardial contractility, development (in predisposed patients) or increased severity of chronic heart failure,rupture of the myocardium after a recent acute infarction.

Vascular disorders:

infrequently - increased blood pressure;

rarely - thromboembolic complications;

very rarely - vasculitis.

Disturbances from the nervous system:

infrequently - increase intracranial pressure (pseudo-tumor of the brain) after the abolition of therapy, dizziness, headache, vertigo, neuropathy, insomnia, hyperkinesia;

very rarely seizures, manifestation of latent or worsening of the course of established epilepsy.

Disorders from the psyche:

rarely - psychoses; changes in personality and behavior, irritability, depression; propensity to suicidal thoughts, euphoria, anxiety, hallucinations, emotional lability.

Disorders from the endocrine system:

often adrenal insufficiency, pituitary insufficiency (especially against stress), decreased glucose tolerance, steroid diabetes mellitus, the transition of latent diabetes mellitus to a clinically manifested, increased need for insulin or oral hypoglycemic drugs in patients with diabetes mellitus, Isenko- Cushing's, hirsutism, growth retardation in children.

Disorders from the metabolism and nutrition:

often - weight gain, obesity, hyperglycemia, sodium and water retention, increased potassium loss;

infrequently hypertriglyceridemia; very rarely hypokalemic alkalosis, negative nitrogen balance. Epidural lipomatosis (with systemic therapy of GCS).

Disorders from the gastrointestinal tract:

discomfort in the epigastric region, bloating;

infrequently - nausea, hiccough, "steroid" stomach or duodenal ulcer;

very rarely - erosive esophagitis, perforation of the walls of the stomach or intestines and gastrointestinal bleeding (hematemesis, melena), especially in patients with chronic inflammatory diseases of the large intestine.

Disturbances from the liver and bile ducts:

rarely - increased activity of "liver" transaminases;

very rarely - perforation of gallbladder walls.

Disturbances from musculoskeletal and connective tissue:

often - muscle atrophy, osteoporosis, muscle weakness, "steroid" myopathy (muscle weakness due to catabolism of muscle tissue);

infrequently - aseptic necrosis of bones;

very rarely - compression fractures of the vertebrae, tendon ruptures (especially when combined with certain quinolones), articular cartilage damage and bone necrosis (with frequent intraarticular injections).

Disturbances from the skin and mucous membranes:

often - delayed healing of wounds, striae, petechiae and ecchymosis, increased sweating, acne, suppression of skin reaction during allergological tests, erythema, thinning of the skin;

very rarely - angioedema, allergic dermatitis, urticaria. Teleangiectasia, hypertrichosis, rosaceous-like perioral dermatitis.

Disturbances on the part of the organ of sight:

infrequently - edema of the disc optic nerve, "steroid" cataract, glaucoma, increased intraocular pressure;

very rarely - exophthalmos, secondary eye infections, retinopathy, central serous chorioretinopathy. Trophic changes of the cornea, chemosis, ptosis, mydriasis, perforation of the cornea against the background of already existing keratitis.

Violations of the genitals and mammary gland:

irregularity of the menstrual cycle, amenorrhea;

rarely - impotence.

General disorders and disorders at the site of administration:

very rarely - edema, hyper- or hypopigmentation of the skin, atrophy of the skin or subcutaneous tissues, "sterile" abscesses and redness of the skin, burning sensation at the injection site, arthropathy.

The "cancellation" syndrome: If a patient taking long-term glucocorticosteroids rapidly decreases the dose of the drug, signs of adrenal insufficiency may develop, which may be accompanied by a decrease in blood pressure and cause the patient to die. It is also possible to develop a withdrawal syndrome not associated with adrenal insufficiency (anorexia, nausea, vomiting, lethargy, headache, fever, arthralgia, desquamation of the epithelium, myalgia, weight loss, lowering blood pressure). In some cases, the "cancellation" syndrome may be similar to the symptoms of the disease over which the patient was treated with the drug dexamethasone. With the development of severe adverse events, treatment with dexamethasone should be discontinued.

Overdose:

Symptoms: It is possible to strengthen the side effects described above. Increased blood pressure, edema, peptic ulcer, hyperglycemia, impaired consciousness.

Treatment: symptomatic.

There is no specific antidote.Hemodialysis is ineffective.

Interaction:

The pharmaceutical incompatibility of Dexamethasone with other intravenously administered drugs is possible - it is recommended to administer it separately from other drugs (iv bolus, or via another drip as a second solution). When a solution of dexamethasone is mixed with heparin, a precipitate forms.

Simultaneous administration of Dexamethasone with:

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

- diuretics (especially "thiazide" and inhibitors carbonic anhydrase) and amphotericin B - can lead to increased excretion from the body of potassium and an increased risk of developing heart failure;

- with sodium-containing preparations - to the development of edema and increased blood pressure;

- cardiac glycosides - their tolerance is worsened and the likelihood of developing ventricular extrasystole (due to induced hypokalemia) increases;

- indirect anticoagulants - weakens (less intensifies) their effect (dose adjustment is required);

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

- ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) - the risk of erosive and ulcerative lesions in the gastrointestinal tract increases and bleeding develops (in combination with NSAIDs, a decrease in the dose of glucocorticosteroids due to the summation of the therapeutic effect is possible in the treatment of arthritis);

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

- acetylsalicylic acid - accelerates its excretion and reduces the concentration in the blood (with the dexamethasone withdrawal, the level of salicylates in the blood increases and the risk of developing side effects increases);

- insulin and oral hypoglycemic drugs, antihypertensive drugs - their effectiveness decreases;

- vitamin D - its effect on calcium absorption in the intestine decreases;

- somatotropic hormone - reduces the effectiveness of the latter, and with praziquantel - its concentration;

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

- isoniazid and mexelitone - increases their metabolism (especially in "slow" acetylators), which leads to a decrease in their plasma concentrations.

Inhibitors of carbonic anhydrase and looped diuretics can increase the risk of osteoporosis.

Indomethacin, displacing dexamethasone from association with albumin, increases the risk of developing its side effects.

ACTH increases the effect of dexamethasone.

Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by dexamethasone.

Cyclosporine and ketoconazole, slowing the metabolism of dexamethasone, can in some cases increase its toxicity.

Simultaneous appointment of androgens and steroid anabolic drugs with dexamethasone promotes the development of peripheral edema and hirsutism, the appearance of acne.

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

Mitotane and other inhibitors of the adrenal cortex function may necessitate an increase in the dose of dexamethasone.

With simultaneous use with live antiviral vaccines and against other types of immunizations, increases the risk of virus activation and the development of infections.

Antipsychotic drugs (antipsychotics) and azathioprine increase the risk of developing cataract in the appointment of dexamethasone.

With simultaneous use with antithyroid drugs is reduced, and with thyroid hormones - increases the clearance of dexamethasone.

Special instructions:

Before the beginning of treatment (if it is impossible due to the urgency of the condition - during the 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 long-term) it is necessary to observe the oculist, control blood pressure and condition of the water-electrolyte balance, as well as patterns of peripheral blood and blood glucose levels.

To reduce side effects, you should increase the intake of potassium 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. the patients should be carefully monitored for one year after the end of a long dexamethasone in connection with the possible development of relative adrenal insufficiency in stressful situations.

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.

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 content of metabolites of 11- and 17-oxyketocorticosteroids.

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

Given the likelihood of side effects from the central nervous system, care should be taken when driving vehicles and working with moving mechanisms.

Form release / dosage:

Solution for intravenous and intramuscular injection, 4 mg / ml.

Packaging:

1 ml per ampoule of neutral glass.

For 10 ampoules with instructions for use and a knife for opening ampoules or a scarifier ampoule in a box of cardboard.

By 5 or 10 ampoules per contour cell pack of polyvinylchloride film or polyethylene terephthalate tape and aluminum foil or paper with polyethylene coating, or without foil, or without paper.

For 1 or 2 contour packs with instructions for use and a knife for opening ampoules or a scarifier ampullum in a pack of cardboard. When you pack the ampoules with a break ring or break point, the ampoule opener or ampoule scapper is not put in.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

1 year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002011/09

Date of registration:17.03.2009 / 12.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:NOVOSIBHIMFARM, OJSC NOVOSIBHIMFARM, OJSC Russia

Manufacturer: & nbsp

NOVOSIBHIMFARM, OJSC Russia

Representation: & nbspNOVOSIBHIMFARM, OJSCNOVOSIBHIMFARM, OJSC

Information update date: & nbsp22.04.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)