Betamethasone

General characteristics. Structure:

Active ingredient: 1 mg of betamethasone in 1 ml of suspension.

The drug rendering glucocorticoid, antiinflammatory, antiallergic, antipruritic action.

Pharmacological properties:

Pharmacodynamics. Interacts with specific receptors in cell cytoplasm, the formed complex gets into a cell kernel, contacts DNA and stimulates synthesis of MRNK inducing formation of proteins including the lipokortin mediating cellular effects. In some cells (for example in lymphocytes) causes MRNK suppression. Lipokortin oppresses A2 phospholipase, blocks a liberation of arachidonic acid and biosynthesis of the endoperoxides, PG, leukotrienes (promoting development of an inflammation, an allergy and other pathological processes).

Influences all phases of an inflammation. The antiinflammatory effect is caused by many factors. One of leaders is A2 phospholipase inhibition  with the subsequent oppression of formation of pro-inflammatory mediators — PG and leukotrienes. Besides, stabilizes cellular membranes, including membranes of lysosomes, prevents an exit of lizosomalny enzymes and reduces their concentration in the inflammation center. Slows down migration of neutrophils and macrophages in the center of an inflammation and their phagocytal activity. Improves microcirculation, reduces permeability of vessels, causes vasoconstriction of capillaries, reduces liquid exudation.

Antiallergic action develops as a result of decrease in synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine and other biologically active agents, reduction of number of the circulating basophiles, suppression of proliferation of adenoid and connecting tissue, reduction of number of T - and B-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.

The immunodepressive effect is connected with suppression of activity of T - and B-lymphocytes, and also braking of release of cytokines (interleykina-1, interleykina-2, interferon - gamma) from leukocytes and macrophages.

Antishock and anti-toxic action is connected with increase in the ABP (due to increase in quantity of the circulating catecholamines, recovery of sensitivity of adrenoceptors to catecholamines and vasoconstriction), activation of the enzymes of a liver participating in metabolism endo-and xenobiotics.

Exerts the expressed impact on all types of exchange. Stimulates a gluconeogenesis in a liver, increases glucose level in blood (the glucosuria is possible). Accelerates a catabolism of proteins, especially in muscular tissue. Causes fat redistribution: raises a lipolysis in tissues of extremities, promotes fat accumulation preferential in a face (a crescent-shaped face), a neck, a shoulder girdle. Na + detains  and water, removal of K+ stimulates, increases removal of Ca+.

At prolonged use the hypothalamus — a hypophysis — adrenal glands suppresses function of system.

Pharmacokinetics. After parenteral (in oil) and enteral administration it is quickly soaked up — the maximum effect (at intake) develops in 1–2 h.

When using a combination of salts in one drug of betamethasone of dinatrium phosphate is well soaked up from an injection site and has bystry effect, betamethasone Dipropionas has slower absorption, but provides effect duration.

At an instillation in a conjunctival sac gets into intraocular liquid, a cornea, an iris, an eye choroid, a ciliary body, a retina. Children can have a considerable system absorption only at use in high doses or at prolonged use.

At local application on skin intensity of absorption depends on a number of factors: solvent (polypropylene components improve diffusion), a condition of an epidermal barrier (the inflammation and skin diseases increase absorption).

Contacts proteins of plasma. Easily passes gistogematichesky barriers, including placental. It is partially allocated with breast milk. It Biotransformirutsya preferential in a liver, the formed metabolites are inactive. It is excreted by kidneys.

Carcinogenicity, mutagenicity, influence on fertility. Long researches on animals for the purpose of assessment of potential carcinogenicity or influence on fertility of betamethasone for topical administration are not conducted. Betamethasone was genotoksichny in vitro in the test of aberation chromosomes on lymphocytes of the person (at metabolic activation) and in vivo in micronuclear test on marrow of mice.

Indications to use:

Solution for injections, suspension for injections. Shock (burn, traumatic, operational, toxic, cardiogenic, hemotransfusionic, anaphylactic); allergic (acute, severe forms) and anaphylactoid reactions; wet brain (including against the background of a tumor of a brain or connected with surgical intervention, radiation therapy or an injury of the head); bronchial asthma (severe form), asthmatic status; general diseases of connecting fabric: system lupus erythematosus, pseudorheumatism; acute adrenal insufficiency; thyrocardiac crisis; acute hepatitis, hepatic coma; poisoning with the cauterizing liquids (reduction of the inflammatory phenomena and the prevention of cicatricial narrowings).

Intra joint introduction: a pseudorheumatism, the psoriasis arthritis ankylosing a spondylitis, a disease of Reuters, an osteoarthrosis (in the presence of the expressed signs of an inflammation of a joint, a synovitis).

Tablets. General diseases of connecting fabric: system lupus erythematosus, scleroderma, nodular periarteritis, dermatomyositis, pseudorheumatism; acute and chronic inflammatory diseases of joints: gouty and psoriasis arthritis, juvenile arthritis, an osteoarthrosis (including posttraumatic), nonspecific tendosinovit polyarthritis, the humeroscapular periarteritis ankylosing a spondylarthritis (Bekhterev's disease), Steel's syndrome at adults, a bursitis, a synovitis and an epicondylitis; acute rheumatism, rheumatic carditis, hysterical chorea; bronchial asthma; acute and chronic allergic diseases: allergic reactions to HP and foodstuff, medicinal dieback, serum disease, small tortoiseshell, allergic rhinitis, pollinosis, Quincke's edema; skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, contact dermatitis (with defeat of a big surface of skin), a toxidermia, seborrheal dermatitis, exfoliative dermatitis, a toxic epidermal necrolysis (Lyell's disease), violent herpetiform dermatitis, a malignant exudative erythema (Stephens-Johnson's syndrome); wet brain (traumatic, postoperative, metastatic) after preliminary parenteral use; allergic diseases of eyes: allergic helcomas, allergic forms of conjunctivitis; inflammatory diseases of eyes: sympathetic ophthalmia, heavy slow lobbies and back uveites, optic neuritis; inborn adrenal struma; primary or secondary adrenal insufficiency (including a state after removal of adrenal glands); diseases of kidneys of autoimmune genesis (including acute glomerulonephritis), nephrotic syndrome; subacute thyroiditis; diseases of bodies of a hemopoiesis: an agranulocytosis, a panmyelopathia, autoimmune hemolitic anemia, inborn (erythroidal) hypoplastic anemia, acute lympho-and myeloid leukoses, a lymphogranulomatosis, a Werlhof's disease, secondary thrombocytopenia at adults, an eritroblastopeniya (erythrocyte anemia); intersticial diseases of lungs: acute alveolitis, pneumosclerosis, sarcoidosis of the II-III Art.; tubercular meningitis, a pulmonary tuberculosis, aspiration pneumonia (in a combination to specific chemotherapy), a berylliosis, Leffler's syndrome (which is not giving in to other therapy), lung cancer (in a combination with cytostatics); multiple sclerosis; gastrointestinal diseases: ulcer colitis, disease Krone, local enteritis; hepatitis, hypoglycemic states; prevention of reaction of graft rejection; a hypercalcemia owing to malignant new growths, nausea and vomiting when performing cytostatic therapy; multiple myeloma.

At use on skin: dermatitis (simple, exfoliative, solar, seborrheal, radiation, herpetiform, contact, atopic, etc.), eczema (children's, monetovidny, etc.), psoriasis, knotty a prurigo of the Guide, red flat deprive, a skin itch, a diskoidny lupus erythematosus, a small tortoiseshell, a mnogoformny exudative erythema, a generalized erythrosis (as a part of complex therapy), a pemphigus, fungoid mycosis and other skin diseases.

Drops eye and ear: allergic and inflammatory diseases of eyes, including allergic blepharitis, conjunctivitis, keratoconjunctivitis, sclerite, uveitis, chorioretinitis, sympathetic iridocyclitis, central retinitis; optic neuritis, retrobulbar neuritis, outside otitis.

Route of administration and doses:

Inside, parenterally, locally. The way of introduction and the mode of dosing are selected individually depending on character and disease severity, a condition of the patient and the response to the carried-out treatment.

Inside: a daily dose for adults — 0,25–8 mg, for children — 0,017–0,25 mg/kg. After long therapy the dose is reduced gradually.

Parenterally. Dinatrium betamethasone phosphate: — in/in struyno, slowly or kapelno, the adult: a single dose of 4-8 mg (if necessary — 20 mg), then in a maintenance dose — 2–4 mg. Betamethasone Dipropionas — in oil, deeply, adult — 4–6 mg (to 9 mg) in days. To children — in oil, aged from 1 year up to 5 years — an initial dose of 2 mg, 6–12 years — 4 mg. Vnutrisustavno and periartikulyarno (adult): in big joints — 2–4 mg (to 9 mg), small — 0,8–2 mg are not more often than 1 time in 3 weeks; in a synovial bag — 2–3 mg, tendinous vaginas — 0,4–1 mg; soft tissues — 2–6 mg; defeats, boiled and smoked in the center — 0,1 mg/cm2  are (no more), no more than 2 mg a week; in case of need mix with local anesthetics (1% solution of lidocaine, Procainum).

Subkonjyunktivalno, in ophthalmology: if necessary enter 2 mg in the form of solution for injections.

Locally: apply on affected areas of skin with a thin layer and carefully rub (ointment, cream) from 2 to 6 times a day before clinical improvement, then — 1–2 times a day; cream is recommended to be applied on the wet or becoming wet surfaces, ointment — at dry lishayny or scaly defeats. A course of treatment at children and patients with damage of a face — no more than 5 days.

Drops eye and ear: at diseases of eyes, in a conjunctival sac — on 1–2 drops of 0,1% of solution each 1–2 h at the beginning of therapy, at ear diseases, in outside acoustical pass — on 2–3 drops of 0,1% of solution each 2–3 h, in the subsequent depending on therapeutic effect reduce frequency rate of use.

Features of use:

Use at pregnancy and feeding by a breast. At pregnancy it 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); contraindicated — at a preeclampsia, an eclampsia, existence of symptoms of defeat of a placenta. It is not necessary to use often, in high doses, throughout a long span.

Potential teratogenecity of betamethasone of Dipropionas at cutaneous use was not estimated. Teratogenecity of betamethasone of Dipropionas at rabbits at introduction in oil in doses of 0,05 mg/kg is shown. The recorded disturbances included umbilical hernia, to the tsefalotsela, a wolf mouth.

Category of action on a fruit on FDA — C. The feeding women are recommended to stop either breastfeeding, or betamethasone use (especially in high doses).

Mental disturbances are more probable at patients with the chronic diseases contributing to development of these disturbances and at reception of high doses; symptoms can appear during the period of several days to 2 weeks after the beginning of therapy.

With care use at a diabetes mellitus, a cornea herpes simplex, a system lupus erythematosus (the risk of an aseptic necrosis increases), osteoporosis, patients with risk have fibrinferment (appoint against the background of anticoagulants), at elderly (the risk of arterial hypertension, osteoporosis, especially at women in the postclimacteric period is increased), only against the background of the corresponding antibacterial therapy — at abscesses, purulent infections, tuberculosis. It is necessary to consider strengthening of action at a hypothyroidism, cirrhosis, probability of development (especially at prolonged use) relative adrenal insufficiency (within several months after drug withdrawal).

At prolonged treatment it is necessary to watch carefully dynamics of growth and development in children, to periodically conduct ophthalmologic examination (for detection of glaucoma, a cataract, etc.), to regularly control function гипоталамо - pituitary and adrenal system, the content of glucose in blood and urine (especially at patients with a diabetes mellitus), electrolytes in serum, the occult blood in excrements. At system use control of EEG is recommended.

It is necessary to avoid hit in eyes and on a mucous membrane of dosage forms for use on skin.

During therapy vaccination and immunizations avoid. It is not necessary to take alcoholic drinks.

Side effects:

Frequency of development and expressiveness of side effects depend on duration of use and size of the used dose. High doses or prolonged use of group of companies can cause the expressed manifestation mineralo-and the glucocorticoid effects considered as collateral.

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 papilledema (a cerebellum pseudoneoplasm) — usually after treatment, a sleep disorder, dizziness, вертиго, a headache, sudden loss of sight (at parenteral administration in the head, a neck, nasal sinks, head skin perhaps owing to adjournment of crystals of substance in eye vessels), 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.

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, a hypopotassemia, 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, 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.

From integuments: steroid eels, striya, thinning of skin, hyper - or hypopigmentation, petechias and an ecchymoma, the slowed-down healing of wounds, the increased perspiration.

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, disturbance of a regularity of periods, withdrawal (anorexia, nausea, block, muscle or joints, spin pain, abdominal pain, general weakness, etc.).

At in introduction: arrhythmia, rushes of blood to the person, spasms.

At intra joint introduction: strengthening of pain in a joint.

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; an atrophy of skin and hypodermic cellulose (at introduction in oil).

At use on skin: itch, hyperemia, burning and xeroderma, erythema, steroid eels, striya, folliculitis, hypertrichosis, heat rash, consecutive infections of skin and mucous membranes; at prolonged use — a skin atrophy, a local hirsutism, a teleangiectasia, a purpura, hypopigmentation; when drawing on big surfaces system manifestations (gastritis, an ulceration of a mucous membrane of a GIT) are possible.

Drops eye and ear: increase in intraocular pressure, glaucoma, formation of a back subkapsulyarny cataract, thinning or perforation of a cornea, sclera; a burning sensation and prickings in an ear; irritation, pain, itch and burning of skin; dermatitis, development of consecutive infection, at prolonged use in high doses — development of systemic action of group of companies.

Interaction with other medicines:

Therapeutic, toxic effects reduce inductors of enzymes of a liver, strengthen — estrogen and peroral contraceptives, the probability of arrhythmias and a hypopotassemia raise the foxglove glycosides, diuretics (causing deficit of potassium), B Amphotericinum, karboangidraza inhibitors; risk of ulcer and erosive defeats or bleedings in a GIT — alcohol and NPVS; probability of infections and development of lymphoma and other limfoproliferativny diseases — immunodepressants, possibility of a fluid lungs at pregnant women — Ritodrinum.

Weakens hypoglycemic activity of antidiabetic means and insulin, natriuretic and diuretic — diuretic, activity of vaccines (because of decrease in development of antibodies); anti-coagulative — derivative coumarin and an indandion, heparin, Streptokinasa and an urokinase. Increases a paracetamol hepatotoxic.

Reduces concentration in blood of salicylates, a meksiletin.

Contraindications:

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

For system use (parenterally and inside): system mycoses, herpetic diseases, including chicken pox, and also measles (now or recently postponed, including recent contact with the patient), the strongyloidosis (established or suspected), tuberculosis (an active form in the absence of specific treatment, latent), immunodeficiency (including AIDS or HIV infection), gastrointestinal diseases (including a round ulcer, a peptic ulcer of a stomach and duodenum in an aggravation phase, a diverticulitis, an esophagitis, gastritis, recently created intestines anastomosis), diseases of cardiovascular system (including recently postponed myocardial infarction, congestive heart failure, arterial hypertension), a diabetes mellitus (including disturbance of tolerance to glucose), myastenia gravis, acute psychosis, a renal/liver failure, the vaccination period.

For intra joint introduction, in the defeat center: 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.

At use on skin: skin displays of syphilis, tuberculosis cutis; bacterial, viral, fungus skin diseases (including chicken pox, herpes); the trophic ulcers of a shin connected with a varicosity; carcinoma cutaneum, nevus, atheroma, melanoma, hemangioma, xanthoma, sarcoma; a rozatsea and ordinary eels (the exacerbation of a disease is possible), postvaccinal skin reactions, children till 1 year have a rash (against the background of an intertrigo).

Drops eye and ear: fungal infections of eyes or an ear, acute viral diseases of eyes (including the acute superficial keratitis caused by Herpes simplex) or fish soup, tubercular damage of eyes (including in the anamnesis) or fish soup, bacterial infections of eyes or an ear, thinning or existence of defect of an epithelium of a cornea, sclera; glaucoma, existence of the chronic or postponed earlier average otitis, perforation of a tympanic membrane (ototoxicity development is possible).

Restrictions to use. For system use (parenterally and inside): open angle glaucoma, lipidemia, hypoalbuminemia, viral and bacterial infections, syphilis, Itsenko-Cushing's disease, system osteoporosis, thrombophlebitis, obesity of the III-IV degree.

For intra joint introduction: the general serious condition of the patient, inefficiency or short duration of action of 2 previous introductions (taking into account individual properties of the applied groups of companies).

At use on skin: at prolonged use or drawing on big surfaces — a cataract, a diabetes mellitus, glaucoma, tuberculosis.

Children's age: at children in a growth period apply only according to absolute indications.

Overdose:

Symptoms: nausea, vomiting, frustration of a dream, euphoria, excitement. At prolonged use in high doses — osteoporosis, a liquid delay in an organism, increase in the ABP and other signs of a hypercorticoidism, including an Icenco-Cushing syndrome, secondary adrenal insufficiency.

Treatment: against the background of gradual drug withdrawal maintenance of the vital functions, correction of electrolytic balance, antacids, fenotiazina, lithium drugs; at an Icenco-Cushing syndrome — аминоглутетимид.

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:

Injection suspension on 1 ml in each ampoule. On 1, 5 or 10 ampoules, together with the application instruction in cardboard packaging.