Dexamethasone

General characteristics. Structure:

Active ingredient: 0,5 mg of dexamethasone in 1 tablet.

The drug rendering a glucocorticoid, antiinflammatory, antiallergic, antishock, immunodepressive effect.

Pharmacological properties:

Pharmacodynamics. Interacts with specific cytoplasmatic receptors and forms the complex getting into a cell kernel; causes an expression or a depression of MRNK, changing education on ribosomes of the proteins, including a lipokortina mediating cellular effects. Lipokortin oppresses A2 phospholipase, suppresses a liberation of arachidonic acid and inhibits biosynthesis of endoperoxides, PG, the leukotrienes promoting processes of an inflammation, an allergy, etc. Interferes with release of mediators of an inflammation from eosinophils and mast cells. Brakes activity of hyaluronidase, a collagenase and proteases, normalizes functions of an intercellular matrix of a cartilaginous and bone tissue.

Reduces permeability of capillaries, stabilizes cellular membranes, including lizosomalny, release of cytokines (interleykin 1 and 2, gamma interferon) from lymphocytes and macrophages oppresses. Influences all phases of an inflammation, the anti-proliferative effect is caused by braking of migration of monocytes in the inflammatory center and proliferation of fibroblasts. Causes involution of an adenoid tissue and a lymphopenia that causes an immunosuppression. Except reduction of number of T lymphocytes, their influence on V-lymphocytes decreases and production of immunoglobulins is slowed down. Influence on system of a complement consists in decrease in education and increase in disintegration of its components. Antiallergic action is a consequence of braking of synthesis and secretion of mediators of an allergy and reduction of number of basophiles. Recovers sensitivity of adrenoceptors to catecholamines.

Accelerates a catabolism of proteins and reduces their content in plasma, reduces glucose utilization by peripheral fabrics and raises a gluconeogenesis in a liver. Stimulates formation of fermental proteins in a liver, surfactant, fibrinogen, erythropoetin, a lipomodulin. Causes fat redistribution (raises a lipolysis of fatty tissue of extremities and an adiposity in an upper half of a trunk and on a face). Promotes formation of higher fatty acids and triglycerides. Reduces absorption and increases calcium removal; detains sodium and water, secretion of AKTG. Possesses antishock action.

Pharmacokinetics. After intake it is quickly and completely soaked up from a GIT, Tmax is 1–2 h. In blood contacts (60–70%) specific protein carrier — transcortinum. Easily passes through gistogematichesky barriers, including GEB and placental. It Biotransformirutsya in a liver (generally by conjugation with glucuronic and sulfuric acids) to inactive metabolites. T1/2 from plasma is 3–4,5 h, T1/2 from fabrics is 36–54 h. It is removed by kidneys and through intestines, gets into breast milk.

After an instillation in a conjunctival sac well gets into an epithelium of a cornea and a conjunctiva, at the same time in watery moisture of an eye therapeutic concentration of HP are created. At an inflammation or injury of a mucous membrane the speed of penetration increases.

Indications to use:

For system use (parenterally and inside). Shock (burn, anaphylactic, posttraumatic, postoperative, toxic, cardiogenic, hemotransfusionic, etc.); brain hypostasis (including at tumors, a craniocereberal injury, neurosurgical intervention, a hematencephalon, encephalitis, meningitis, radiation injury); bronchial asthma, asthmatic status; general diseases of connecting fabric (including system lupus erythematosus, pseudorheumatism, scleroderma, nodular periarteritis, dermatomyositis); thyrocardiac crisis; hepatic coma; poisoning with the cauterizing liquids (for the purpose of reduction of the inflammatory phenomena and the prevention of cicatricial narrowings); acute and chronic inflammatory diseases of joints, including gouty and psoriasis arthritis, osteoarthrosis (including posttraumatic), polyarthritis, the humeroscapular periarthritis ankylosing a spondylarthritis (Bekhterev's disease), juvenile arthritis, Steel's syndrome at adults, a bursitis nonspecific tendosinovit, a synovitis, an epicondylitis; rheumatic fever, acute rheumatic carditis; acute and chronic allergic diseases: allergic reactions to HP and foodstuff, serum disease, small tortoiseshell, allergic rhinitis, pollinosis, Quincke's disease, medicinal dieback; skin diseases: a pemphigus, psoriasis, dermatitis (contact dermatitis with defeat of a big surface of skin, atopic, exfoliative, violent herpetiform, seborrheal, etc.), eczema, a toxidermia, a toxic epidermal necrolysis (Lyell's disease), a malignant exudative erythema (Stephens-Johnson's syndrome); allergic diseases of eyes: allergic helcomas, allergic forms of conjunctivitis; inflammatory diseases of eyes: sympathetic ophthalmia, heavy slow lobbies and back uveites, optic neuritis; primary or secondary adrenal insufficiency (including a state after removal of adrenal glands); inborn adrenal struma; diseases of kidneys of autoimmune genesis (including acute glomerulonephritis), nephrotic syndrome; subacute thyroiditis; diseases of bodies of a hemopoiesis: an agranulocytosis, a panmyelopathia, anemia (including autoimmune hemolitic, inborn hypoplastic, an eritroblastopeniya), an idiopathic Werlhof's disease, secondary thrombocytopenia at adults, a lymphoma (hodzhkinsky, nekhodzhkinsky), leukemia, a lymphoid leukosis (acute, chronic); diseases of lungs: acute alveolitis, pneumosclerosis, sarcoidosis of the II-III Art.; tubercular meningitis, a pulmonary tuberculosis, aspiration pneumonia (only in a combination to specific therapy); a berylliosis, Leffler's syndrome (resistant to other therapy); lung cancer (in a combination with cytostatics); multiple sclerosis; gastrointestinal diseases (for removal of the patient from a critical state): ulcer colitis, disease Krone, local enteritis; hepatitis; prevention of reaction of graft rejection; a tumoral hypercalcemia, nausea and vomiting when performing cytostatic therapy; multiple myeloma; conducting test at differential diagnosis of a hyperplasia (hyperfunction) and tumors of bark of adrenal glands.

For topical administration. Vnutrisustavno, periartikulyarno. A pseudorheumatism, the psoriasis arthritis ankylosing a spondylarthritis, a disease of Reuters, an osteoarthrosis (in the presence of the expressed signs of an inflammation of a joint, a synovitis).

Konjyunktivalno. Conjunctivitis (not purulent and allergic), a keratitis, a keratoconjunctivitis (without damage of an epithelium), an iritis, an iridocyclitis, a blepharitis, blefarokonjyunktivit, an episcleritis, a sclerite, uveites of various genesis, a retinitis, an optic neuritis, retrobulbar neuritis, superficial injuries of a cornea of various etiology (after full epithelization of a cornea), inflammatory processes after injuries of an eye and eye operations, a sympathetic ophthalmia.

In outside acoustical pass. Allergic and inflammatory diseases of an ear, including otitis.

Route of administration and doses:

Inside, parenterally, locally, including konjyunktivalno. The mode of dosing is set individually, depending on indications, by conditions of the patient and his reaction to therapy.

Inside, once, in the morning (a small dose) or in 2–3 receptions (high dose): from 2–3 mg to 4–6 mg (10–15 mg) a day, after achievement of effect the dose is gradually reduced to supporting — 0,5–1 mg (2–4,5 mg and more) in days; treatment is stopped gradually (at the end appoint several injections of corticotropin). To children (depending on age) — 0,0833–0,3333 mg/kg or 0,0025–0,0001 mg/sq.m a day in 3–4 receptions.

Parenterally: in/in, slowly struyno or kapelno (at acute and medical emergencies) or 4–20 mg in oil (to 80 mg) 3–4 times a day, maintenance doses — 0,2–9 mg a day, a course 3–4 days, then — intake. To children — in oil, 0,02776–0,16665 mg/kg each 12–24 h.

Vnutrisustavno (in the defeat center) or periartikulyarno (in soft tissues): to adults and teenagers — 0,2–6 mg (2–8 mg), repeatedly with an interval of 3 days to 3 weeks as required; the maximum dose for adults — 80 mg a day.

Locally. At otitis: on 3–4 drops in the affected ear 2–3 times a day.

Konjyunktivalno: at acute states — on 1–2 drops each 1–2 h, then — in 4–6 h; in other cases — on 1–2 drops 3–4 times a day; a course — from 1–2 days to several weeks (2-5 weeks) depending on a state.

Features of use:

Use of corticosteroids during pregnancy is possible if the expected effect of therapy exceeds potential risk for a fruit (adequate and strictly controlled researches of safety of use were not conducted). Women of childbearing age need to be warned about potential risk for a fruit (corticosteroids pass through a placenta). It is necessary to watch newborns whose mothers during pregnancy received corticosteroids (possibly development of insufficiency of adrenal glands in a fruit and the newborn) carefully.

Teratogenecity of dexamethasone at mice and rabbits after local ophthalmologic applications of repeated therapeutic doses is shown.

Corticosteroids cause a resorption of a fruit and specific disturbance in mice — development of a wolf mouth in posterity. Corticosteroids cause a resorption of a fruit and multiple disturbances, including anomalies of development of the head, ear, extremities, the sky in rabbits, etc.

Category of action on a fruit on FDA — C. The feeding women are recommended to stop either breastfeeding, or use of HP, especially in high doses (corticosteroids get into breast milk and can suppress growth, development of endogenous corticosteroids and to cause undesirable effects in the newborn).

It must be kept in mind that at topical administration of glucocorticoids there is a system absorption.

Appointment in case of intercurrent infections, tuberculosis, septic states demands preliminary and subsequent simultaneous antibacterial therapy.

It is necessary to consider strengthening of action of corticosteroids at a hypothyroidism and cirrhosis, aggravation of psychotic symptomatology and emotional lability at their high initial level, masking of some symptoms of infections, probability of preservation within several months (about one year) relative adrenal insufficiency after dexamethasone cancellation (especially in case of prolonged use).

In stressful situations during the supporting treatment (for example surgery, a disease, an injury) it is necessary to carry out dose adjustment of drug in connection with the increased need for glucocorticoids.

At a long course carefully watch dynamics of growth and development of children, systematically conduct ophthalmologic examinations, control a state гипоталамо - pituitary and adrenal system, glucose level in blood.

Due to the possibility of anaphylactic reactions during parenteral therapy before administration of drug it is necessary to take all precautionary measures (especially at patients with tendency to a medicinal allergy).

Stop therapy only gradually. At sudden cancellation after prolonged treatment development of the withdrawal which is shown fervescence, a mialgiya and an arthralgia, an indisposition is possible. These symptoms can appear even in case insufficiency of bark of adrenal glands is noted.

It is recommended to be careful when carrying out any sort of operations, developing infectious diseases, injuries, to avoid immunization, to exclude the use of alcoholic drinks. At children, in order to avoid overdose, it is better to make calculation of a dose, proceeding from body surface area. In case of contact with patients with measles, chicken pox and other infections appoint the corresponding preventive therapy.

Before use of eye forms of dexamethasone it is necessary to remove soft contact lenses (again it is possible to establish them not earlier than in 15 min.). During treatment it is necessary to control a condition of a cornea and to measure intraocular pressure.

It is not necessary to apply in operating time to drivers of vehicles and people whose profession is connected with the increased concentration of attention.

Side effects:

Frequency of development and expressiveness of side effects depend on duration of use, size of the used dose and a possibility of observance of a circadian rhythm of purpose of HP.

System effects. From a nervous system and sense bodys: a delirium (confusion of consciousness, excitement, concern), a disorientation, euphoria, hallucinations, a maniacal/depressive episode, a depression or paranoia, increase in intracranial pressure with a syndrome of a congestive optic papilla (the brain pseudoneoplasm — is more often at children, usually after too bystry reduction of a dose, symptoms — a headache, deterioration in visual acuity or doubling in eyes); sleep disorder, dizziness, вертиго, headache; sudden loss of sight (at parenteral administration in the head, a neck, nasal sinks, head skin), formation of a back subkapsulyarny cataract, increase in intraocular pressure with possible injury of an optic nerve, glaucoma, a steroid exophthalmos, development of consecutive fungal or viral infections of eyes.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): arterial hypertension, development of chronic heart failure (at predisposed patients), a myocardial dystrophy, hypercoagulation, thrombosis, the ECG changes characteristic of a hypopotassemia; at parenteral administration: rushes of blood to the person.

From bodies of a GIT: nausea, vomiting, GIT erosive cankers, pancreatitis, erosive esophagitis, hiccups, increase/loss of appetite.

From a metabolism: Na delay
+
 and waters (peripheral hypostases), a hypopotassemia, a hypocalcemia, negative nitrogenous balance in connection with a catabolism of proteins, increase in body weight.

From endocrine system: oppression of function of bark of adrenal glands, decrease in tolerance to glucose, a steroid diabetes mellitus or manifestation of a latent diabetes mellitus, an Icenco-Cushing syndrome, a hirsutism, disturbance of a regularity of periods, a growth inhibition at children.

From a musculoskeletal system: muscular weakness, steroid myopathy, decrease in muscle bulk, osteoporosis (including spontaneous fractures of bones, aseptic necrosis of a head of a femur), rupture of sinews; muscle or joints, spin pain; at intra joint introduction: strengthening of pain in a joint.

From integuments: steroid eels, striya, thinning of skin, a petechia and an ecchymoma, the slowed-down healing of wounds, the increased sweating.

Allergic reactions: skin rash, a small tortoiseshell, puffiness of the person, a stridor or the complicated breath, an acute anaphylaxis.

Others: decrease in immunity and activation of infectious diseases, withdrawal (anorexia, nausea, block, abdominal pain, general weakness, etc.).

Local reactions at parenteral administration: burning, numbness, pain, paresthesia and an infection in an injection site, formation of hems in the place of an injection; hyper - or hypopigmentation; an atrophy of skin and hypodermic cellulose (at introduction in oil).

Eye forms: at prolonged use (more than 3 weeks) increase in intraocular pressure and/or development of glaucoma with damage of an optic nerve, decrease in visual acuity and loss of fields of vision, formation of a back subkapsulyarny cataract, thinning and perforation of a cornea is possible; spread of a herpes and bacterial infection is possible; at patients with hypersensitivity to dexamethasone or a benzalkoniya to chloride conjunctivitis and a blepharitis can develop.

Local reactions (at use of eye and/or ear forms): irritation, itch and burning of skin; dermatitis.

Interaction with other medicines:

Barbiturates, Phenytoinum, rifampicin (accelerate metabolism), Somatotropinum, antacids (reduce absorption) reduce therapeutic and toxic effects, strengthen — estrogensoderzhashchy oral contraceptives, risk of arrhythmias and a hypopotassemia — cardiac glycosides and diuretics, probability of hypostases and arterial hypertension — natriysoderzhashchy drugs or additives, a heavy hypopotassemia, heart failure and osteoporosis — Amphotericinum In and karboangidraza inhibitors, risk of erosive cankers and bleedings from a GIT — NPVS.

At simultaneous use with live antiviral vaccines and against the background of other types of immunization increases risk of activation of viruses and development of infections. Weakens hypoglycemic activity of insulin and peroral antidiabetic means, anticoagulating — coumarins, diuretic — diuretic, immunotropny — vaccination (suppresses antibodyformation). Worsens portability of cardiac glycosides (causes deficit of potassium), reduces concentration of salicylates and a prazikvantel in blood.

Contraindications:

Hypersensitivity (for short-term system use according to vital indications is the only contraindication).

For system use (parenterally and inside). System mycoses, parasitic and infectious diseases of the virus or bacterial nature (now without the corresponding chemotherapy or recently postponed, including recent contact with the patient), including the herpes simplex surrounding herpes (a viremichesky phase), the chicken pox, measles, the amebiasis, a strongyloidosis (established or suspected), active forms of tuberculosis; immunodeficiency (including AIDS or HIV infection), the period before and after preventive inoculations (especially antiviral); system osteoporosis, myastenia gravis; gastrointestinal diseases (including a peptic ulcer of a stomach and duodenum, an esophagitis, gastritis, an acute or latent round ulcer, recently created intestines anastomosis, nonspecific ulcer colitis with threat of perforation or abscessing, a diverticulitis); diseases of cardiovascular system, including recently postponed myocardial infarction, congestive heart failure, arterial hypertension; diabetes mellitus, acute renal and/or liver failure, psychosis.

For intra joint introduction. Unstable joints, the previous arthroplasty, pathological bleeding (endogenous or caused by use of anticoagulants), chressustavny a bone fracture, the infected centers of damage of joints, circumarticular soft tissues and intervertebral spaces, the osteoporosis expressed circumarticular.

Eye forms. Virus, fungal and tubercular infections of eyes, including the keratitis caused by Herpes simplex, viral conjunctivitis, an acute purulent eye infection (in the absence of antibacterial therapy), disturbance of integrity of an epithelium of a cornea, trachoma, glaucoma.

Ear forms. Perforation of a tympanic membrane.

Restrictions to use. For system use (parenterally and inside): Itsenko-Cushing's disease, obesity of the III-IV degree, convulsive states, a hypoalbuminemia and states contributing to its emergence; open angle glaucoma.

For intra joint introduction: the general serious condition of the patient, inefficiency or short duration of action of two previous introductions (taking into account individual properties of the applied glucocorticoids).

Overdose:

Symptoms: strengthening of side effects.

Treatment: at development of the undesirable phenomena — symptomatic therapy, at an Icenco-Cushing syndrome — purpose of an aminoglutetimid.

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 0,5 mg, 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.