Dexamethasone (Solution for injection)

Active material: Dexamethasone
When ATH: H02AB02
CCF: GCS for injection
When CSF: 04.02
Manufacturer: M.J.BIOPHARM Pvt.Ltd. (India)

Pharmaceutical form, composition and packaging

Solution for injection clear, colorless or slightly pale-yellow.

Excipients: metilparagidroksiʙenzoat, propilparagidroksibenzoat, sodium metabisulfite, dinatrievaya soly ЭDTA, Sodium hydroxide, water d / and.

2 ml – ampoule (5) – packings Valium planimetric (1) – packs cardboard.
2 ml – ampoule (5) – packings Valium planimetric (2) – packs cardboard.
2 ml – ampoule (5) – packings Valium planimetric (3) – packs cardboard.
2 ml – ampoule (5) – packings Valium planimetric (4) – packs cardboard.
2 ml – ampoule (5) – packings Valium planimetric (5) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES.

Pharmacological action

GCS. It inhibits the function of leukocytes and tissue macrophages. Limit the migration of leukocytes to inflammation. Violates the ability of macrophages to phagocytosis, as well as the formation of interleukin-1. Contributes to the stabilization of lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in inflammation. Decreases capillary permeability, caused by the release of histamine. Inhibits the activity of fibroblasts and collagen formation.

Inhibits the activity of phospholipase A₂, which leads to suppression of the synthesis of prostaglandins and leukotrienes. It suppresses the release of COX (especially COX-2), which also helps to reduce the production of prostaglandins.

It reduces the number of circulating lymphocytes (T- and B-cells), monotsitov, eosinophils and basophils as a result of their displacement from the vascular tissue into the lymphoid; suppresses the formation of antibodies.

Dexamethasone inhibits the release of pituitary ACTH and β-lipotropina, but it does not reduce the level of circulating β-endorphin. It inhibits the secretion of TSH and FSH.

When the immediate application of the receptacles has a vasoconstrictor effect.

Dexamethasone has a pronounced dose-dependent effect on the metabolism of carbohydrates, protein and fat. Stimuliruet gluconeogenesis, promotes the capture of amino acids the liver and kidneys, increases the activity of enzymes gluconeogenesis. The liver dexamethasone enhances the deposition of glycogen, stimulating the activity of glycogen synthesis and glucose from products of protein metabolism. Increased blood glucose activates the secretion of insulin.

Dexamethasone inhibits glucose uptake by fat cells, leading to activation of lipolysis. However, due to an increase in insulin secretion are stimulated lipogenesis, which leads to fat accumulation.

It has catabolic effect in the lymphoid tissue and connective, muscle, fat tissue, skin, bone. Osteoporosis and Cushing's syndrome are the main factors, limits the duration of therapy with corticosteroids. As a result of catabolic actions may suppress growth in children.

At high doses of dexamethasone may increase the excitability of brain tissue and contributes to lowering the threshold of convulsive readiness. It stimulates the excessive production of hydrochloric acid and pepsin in the stomach, that contributes to the development of peptic ulcers.

In the systemic application of therapeutic activity of dexamethasone caused by anti-inflammatory, antiallergic, immunosuppressive and antiproliferative effects.

For external and local application of therapeutic activity of dexamethasone caused by anti-inflammatory, anti-allergic and antiexudativ (thanks vasoconstrictor effect) action.

As anti-inflammatory activity exceeds hydrocortisone 30 time, It has no mineralocorticoid activity.

Pharmacokinetics

Plasma protein binding – 60-70%. It penetrates the blood-tissue barriers. In a small amount excreted in breast milk.

It is metabolized in the liver.

T_1/2 is 2-3 no. Report the news.

The local application in ophthalmology is absorbed through the cornea with intact epithelium moisture in the anterior chamber. When inflammation of the tissues of the eye, or mucosal lesions of the cornea and the rate of absorption of dexamethasone significantly increased.

Testimony

Orally: Biermer's disease; acute and subacute thyroiditis, gipotireoz, progressive ophthalmopathy, associated with thyrotoxicosis; bronchial asthma; rheumatoid arthritis in the acute phase; NYAK; connective tissue diseases; autoimmunnyye gyemolitichyeskiye anyemii, thrombocytopenia, aplasia and hypoplasia of hematopoiesis, agranulocytosis, serum sickness; acute erythroderma, pemphigus (normal), acute eczema (at the beginning of treatment); malignancy (as palliative therapy); congenital adrenogenital syndrome; cephaledema (usually after a preliminary parenteral corticosteroids).

For parenteral administration,: the shock of different genesis; cephaledema (at brain tumor, traumatic brain injury, neurosurgery, a brain haemorrhage, éncefalite, meninges, radiation injury); asthmatic status; severe allergic reactions (angioedema, bronchospasm, dermatosis, severe anaphylactic reaction to a medication, transfusion serum, pyrogenic reactions); acute hemolytic anemia, thrombocytopenia, Acute lymfoblastnaya leykemyya, agranulocytosis; serious infectious disease (in conjunction with antibiotics); acute adrenal insufficiency; Acute croup; arthropathy (frozen shoulder, epicondylitis, styloiditis, ʙursit, tendinitis, kompressionnaya neuropathy, osteochondrosis, arthritis of various etiologies, osteoarthritis).

For use in ophthalmic practice: purulent and allergic conjunctivitis, keratit, keratoconjunctivitis without damaging the epithelium, Irit, iridocyclitis, blefarokonъyunktyvyt, .Aloe, episcleritis, scleritis, inflammation after eye injuries and surgical interventions, transferred ophtalmia.

Dosage regimen

Individual. Inside with severe disease at the beginning of treatment prescribed to 10-15 mg / day, maintenance dose may be 2-4.5 mg or more per day. The daily dose is divided into 2-3 admission. In small doses taken 1 time / day in the morning.

For parenteral administration are administered in / in slow bolus or infusion (acute and urgent conditions); / m; it is also possible periarticular and intra-articular injection. Within one day can be administered by 4 to 20 mg dexamethasone 3-4 times. The duration of parenteral administration is generally 3-4 day, then move on to maintenance therapy with oral form. In the acute phase in various diseases and early treatment dexamethasone used in higher doses. Upon reaching the effective dose reduces an interval of several days to reach the maintenance dose or discontinuation of treatment to.

When used in ophthalmology in acute conditions instilled into the conjunctival sac of 1-2 drop. every 1-2 no, then, while reducing inflammation, every 4-6 no. Duration of treatment 1-2 days to several weeks, depending on the clinical course of the disease.

Side effect

On the part of the endocrine system: reduced glucose tolerance, steroid diabetes or a manifestation of latent diabetes mellitus, adrenal suppression, Cushing's syndrome (incl. moon face, obesity, pituitary type, girsutizm, increased blood pressure, dysmenorrhoea, amenorrhea, myasthenia, striae), delayed sexual development in children.

Metabolism: increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased perspiration, gipernatriemiya, kaliopenia.

CNS: delirium, disorientation, euphoria, hallucinations, affective insanity, depression, paranoia, intracranial hypertension, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebellum, headache, convulsions.

Cardio-vascular system: Arrhythmia, bradycardia (up to heart failure); development (in predisposed patients) or increased severity of chronic heart failure, ECG changes, typical of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. Patients with acute and subacute myocardial infarction – spread necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle; when intracranial introduction – nose bleed.

From the digestive system: nausea, vomiting, pancreatitis, Steroid ulcers of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, Ikotech; rarely – increase in liver transaminases and alkaline phosphatase.

From the senses: zadnyaya subkapsulyarnaya cataracts, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos.

On the part of the musculoskeletal system: slowing growth and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (rarely – pathological fractures, aseptic necrosis of the humeral head and femur), muscle tendon rupture, steroidnaya myopathy, reduced muscle mass (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymosis, thinning of the skin, Hyper- or hypopigmentation, steroid acne, striae, propensity to development of pyoderma and candidiasis.

Allergic reactions: Generalized (incl. skin rash, itchy skin, anaphylactic shock) and topically.

Effects, associated with immunosuppressive effect: development or exacerbation of infection (the appearance of this side effect contribute jointly used immunosuppressants and vaccination).

Local reactions: when administered parenterally – necrosis.

When applied topically: rarely – itch, hyperemia, burning, dryness, folliculitis, acne, gipopigmentatsiya, perioral dermatitis, atopic dermatitis, maceration of the skin, consecutive infection, skin atrophy, striae, jerseys. With prolonged use, or applied to extensive areas of skin may develop systemic side effects, characteristic of the GCS.

Contraindications

For short-term use for health reasons – Hypersensitivity to dexamethasone.

For intraarticular administration and the introduction of directly to the lesion: previous arthroplasty, abnormal bleeding (endogenous or caused by the use of anticoagulants), intra-articular fracture, infectious (septic) inflammation in the joints and periarticular infections (incl. history), as well as common infectious disease, marked periarticular osteoporosis, no signs of inflammation in the joint (“dry” joint, eg osteoarthritis without synovitis), marked bone destruction and deformity of the joint (sharp narrowing of the joint space, ankiloz), instability of the joint as a result of arthritis, aseptic necrosis of the formative joint epiphyses of bones.

For outdoor use: Bacterial, Viral, fungal skin diseases, lupus, cutaneous manifestations of syphilis, skin tumors, post-vaccination period, violation of the integrity of the skin (ulcers, wounds), childhood (to 2 years, itching in the anal area – to 12 years), Rosacea, acne vulgaris, perioral dermatitis.

For the use in ophthalmology: Bacterial, Viral, fungal diseases of the eye, ocular tuberculosis, violation of the integrity of the epithelium of the eye, acute form of purulent eye infection in the absence of specific therapy, corneal disease, combined with epithelial defects, trachoma, glaucoma.

Pregnancy and lactation

When pregnancy (especially in the I trimester), and lactation dexamethasone is used with the anticipated therapeutic effect and adverse effects on the fetus. When long-term therapy in pregnancy has not ruled out the possibility of violations of fetal growth. In the case of late pregnancy there is a risk of atrophy of the adrenal cortex fetus, which may require replacement therapy in the newborn.

Cautions

C care should be used when parasitic and viral infections, fungal or bacterial origin (currently or recently transferred, including the recent contact with a patient) – herpes simplex, herpes zoster (viremicheskaya phase), enable vetryanaya, kor, ameʙiaz, strongiloidoz (or suspected), systemic mycosis; active and latent tuberculosis. Application for serious infectious diseases is permissible only against the background of specific therapy.

Caution should be used for 8 weeks before and 2 weeks after vaccination, when lymphadenitis after BCG vaccination, with immunodeficiency (incl. AIDS or HIV infection).

Caution should be used in diseases of the digestive tract: gastric ulcer and duodenal ulcer, эzofagite, gastritis, acute or latent peptic ulcer, recently established intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess, diverticulum.

Caution should be used in diseases of the cardiovascular system, incl. after recent myocardial infarction (in patients with acute and subacute myocardial infarction may spread necrosis, slowing the formation of scar tissue and thereby break the heart muscle), In decompensated chronic heart failure, hypertension, giperlipidemii), in endocrine diseases – diabetes (incl. violation of carbohydrate tolerance), thyrotoxicosis, gipotireoze, Cushing's disease, in severe chronic renal and / or hepatic insufficiency, nefrourolitiaze, with hypoalbuminemia and conditions, predisposing to its occurrence, at systemic osteoporosis, myasthenia, Ostrom psychosis, obesity (III-IV degrees), when polio (except bulbar form of encephalitis), openly- and angle-closure glaucoma.

If necessary, intraarticular administration should be used with caution in patients with severe general condition, ineffectiveness (or short-term) actions 2 predыduschyh introduced (taking into account the individual properties used GCS).

Before and during the treatment of GCS is necessary to control blood count, glycaemia and plasma electrolytes.

When intercurrent infections, septic conditions and tuberculosis, must be simultaneous antibiotic.

Dexamethasone-induced relative adrenal insufficiency may persist for several months after its cancellation. Considering this, in stressful situations, occurring during the period, hormone therapy resume with simultaneous appointment of salts and / or mineralocorticoid.

When applying dexamethasone in patients with herpes cornea should have in mind the possibility of its perforation. In the course of treatment is necessary to control intraocular pressure and corneal.

With the sudden cancellation of dexamethasone, especially in the case of the prior use of high doses of a so-called withdrawal syndrome (not due gipokortitsizm), manifesting anorexia, toshnotoy, retardation, generalized musculoskeletal pain, general weakness. After the cancellation of dexamethasone in a few months can be maintained relative adrenal insufficiency. If during this period there are stressful situations, appointed (on indications) at the time of the SCS, optionally in combination with a mineralocorticoid.

During treatment requires monitoring of blood pressure, water and electrolyte balance, peripheral blood and plasma glucose levels, as well as the observation of an ophthalmologist.

In children during long-term treatment requires careful monitoring of the dynamics of growth and development. Babies, that during treatment in contact with patients with measles or chickenpox, prophylactically prescribe specific immunoglobulins.

Drug Interactions

While the use of antipsychotics, ʙukarʙanom, AZA is a risk of cataracts; with means, okazыvayushtimi antiholinergicheskoe action – the risk of glaucoma.

In an application with dexamethasone reduced the effectiveness of insulin and oral hypoglycemic drugs.

While the use of hormonal contraceptives, androgenic, Estrogen, anabolic steroids can hirsutism, acne.

While the use of diuretics may increase excretion of potassium; NSAIDs (incl. acetylsalicylic acid) – increased incidence of erosive and ulcerative lesions and bleeding from the gastrointestinal tract.

In an application with oral anticoagulants may weaken the anticoagulant effect.

In an application with cardiac glycosides possible deterioration of cardiac glycosides portability because of potassium deficiency.

In an application with aminoglutethimide may decrease or inhibition effects of dexamethasone; with carbamazepine – may reduce the action of dexamethasone; with ephedrine – Dexamethasone increased excretion from the body; with imatinibom – possible to reduce the concentration of imatinib in plasma due to the induction of its metabolism and excretion of increasing.

In an application with itraconazole enhances the effect of dexamethasone; with methotrexate – possibly increased hepatotoxicity; with praziquantel – may decrease the concentration of praziquantel in blood.

In an application with rifampicin, phenytoin, barbiturates may weaken the effects of dexamethasone as a result of increasing its excretion from the body.