Dexamethasone solution for injection 4mg/ml 1ml ampoules, 25pcs

Composition

Active ingredient: Dexamethasone sodium phosphate (dexamethasone phosphate disodium salt) in terms of 100% substance – 4.0 mg

Auxiliary substances:

glycerol (distilled glycerol) – 22.5 mg

disodium edetate (trilon B) – 0.1 mg

sodium hydrophosphate dodecahydrate (sodium phosphate di-substituted 12-water) – 0.8 mg

water for injection-up to 1 ml

Pharmacological action

Synthetic glucocorticoid (GCS), a methylated derivative of fluoroprednisolone. It has anti-inflammatory, anti-allergic, immunosuppressive effects, increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines. It interacts with specific cytoplasmic receptors (GCS receptors are present in all tissues, especially in the liver) to form a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells). Protein metabolism: reduces the amount of globulins in plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin / globulin ratio), reduces protein synthesis and increases catabolism in muscle tissue. Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs mainly in 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 glucose intake 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 metabolism: detains Na+ and water in the body, stimulates the excretion of K+ (mineralocorticoid activity), reduces the absorption of Ca+ from the gastrointestinal tract, reduces bone mineralization. The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils and mast cells; induction of the formation of lipocortins and a decrease in the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes (especially lysosomal) and organelle membranes. It acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes that contribute to the processes of inflammation, allergies, etc. ), the synthesis of “pro-inflammatory cytokines” (interleukin 1, tumor necrosis factor alpha, etc. ); increases the resistance of the cell membrane to various damaging factors. The immunosuppressive effect is due to the induced involution of lymphoid tissue, inhibition of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and interaction of T – and B – lymphocytes, inhibition of the release of cytokines (interleukin-1,2; interferon gamma) from lymphocytes and macrophages, and a decrease in antibody formation. The anti-allergic effect develops as a result of reducing the synthesis and secretion of allergy mediators, inhibiting the release of histamine and other biologically active substances from sensitized mast cells and basophils, reducing the number of circulating basophils, T – and B-lymphocytes, mast cells; suppressing the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, and changing the body’s immune response. In obstructive diseases of the respiratory tract, the effect is mainly due to inhibition of inflammatory processes, prevention or reduction of the severity of mucosal edema, reduction of eosinophilic infiltration of the submucosal layer of the bronchial epithelium and deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucosa. Increases the sensitivity of small and medium-sized bronchial beta-adrenergic receptors to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by reducing its production. Inhibits the synthesis and secretion of ACTH and, secondarily, the synthesis of endogenous corticosteroids. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation. The peculiarity of the action is a significant inhibition of pituitary function and almost complete absence of mineralocorticosteroid activity. Doses of 1-1.5 mg / day inhibit the function of the adrenal cortex; the biological half-life is 32-72 hours (the duration of suppression of the hypothalamic-pituitary-adrenal cortex system. According to the strength of glucocorticoid activity,0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone( or prednisone),15 mg of hydrocortisone, or 17.5 mg of cortisone. Blood-bound pharmacokinetics (60-70%) with a specific carrier protein-transcortin. It easily passes through the histohematic barriers (including the hemato-encephalic and placental ones). It is metabolized 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). T1 / 2 of dexamethasone from plasma-3-5 hours.

Indications

of the disease that require the introduction of fast-acting corticosteroids, as well as cases when oral use of the drug is impossible:

• endocrine diseases: acute adrenal insufficiency, primary or secondary adrenal insufficiency, congenital adrenal hyperplasia, subacute thyroiditis;
• shock (burn, traumatic, surgical, toxic) – the ineffectiveness of a vasoconstrictor, plasma-substituting drugs and other symptomatic therapy;
• swelling of the brain (with brain tumors, head injury, neurosurgical interventions, brain hemorrhage, encephalitis, meningitis, radiation damage);
• asthmatic status; severe bronchospasm (exacerbation of bronchial asthma, chronic obstructive bronchitis);
• severe allergic reactions, anaphylactic shock;
• rheumatic diseases;
• systemic diseases of connective tissue;
• severe acute dermatosis;
• malignant diseases: palliative treatment of leukemia and lymphomas in adults; acute leukemia in children; hypercalcaemia in patients suffering from malignant tumors, failing oral therapy;
• blood disease: acute hemolytic anemia, agranulocytosis, idiopathic thrombocytopenic purpura in adults;
• serious infectious diseases (in combination with antibiotics);
• in ophthalmic practice (subconjunctival, retrobulbar or parabulbarno introduction): allergic conjunctivitis, keratitis, keratoconjunctivitis without epithelial damage, iritis, 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 formation): keloids, discoid lupus erythematosus, ring-shaped granuloma.

Contraindications

For short-term use for vital indications, the only contraindication is hypersensitivity to dexamethasone or the components of the drug.

In children during the growth period, corticosteroids should be used only for absolute indications and under the careful supervision of the attending physician.

With caution, the drug should be prescribed for the following diseases and conditions: :

• diseases of the digestive tract – stomach ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, the newly created anastomosis intestinal ulcerative colitis with the threat of perforation or abecedarian, diverticulitis;
• parasitic and infectious diseases of viral, fungal or bacterial origin (currently or recently transferred, including the recent contact with a patient) – herpes simplex, herpes zoster (vermicella phase), chickenpox, measles; amoebiasis, strongyloidiasis, systemic mycosis, active and latent tuberculosis. 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 (including AIDS or HIV infection);
• cardiovascular disease (including recent myocardial infarction in patients with acute and subacute myocardial infarction possible spread of necrosis, slowing the formation of scar tissue and, as a consequence, rupture of the heart muscle), severe congestive heart failure, hypertension, hyperlipidemia);
• endocrine diseases – diabetes mellitus (including breach of tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, disease Cushing’s, obesity (III-IV degree)
• severe chronic renal and/or hepatic insufficiency, nefrourolitiaz;
• hypoalbuminemia and conditions that predispose to its occurrence;
• systemic osteoporosis, myasthenia gravis, acute psychosis, and polio (except bulbar form of encephalitis), open – and angle-closure glaucoma;
• pregnancy.

Side effects

Dexamethasone is usually well tolerated. It has a low mineralocorticoid activity, i. e. its effect on water-electrolyte metabolism is small. As a rule, low and medium doses of Dexamethasone do not cause sodium and water retention in the body, increased potassium excretion. The following side effects are described:

From the endocrine system: reduced glucose tolerance, steroid diabetes mellitus or latent diabetes mellitus, adrenal suppression, Itsenko-Cushing syndrome (moon-shaped face, pituitary obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcers of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding and perforation of the gastrointestinal tract wall, increased or decreased appetite, digestive disorders, flatulence, hiccups. In rare cases-increased activity of hepatic transaminases and alkaline phosphatase.

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of heart failure, changes in the electrocardiogram characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction-the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

Nervous system disorders: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor of the cerebellum, headache, convulsions.

From the side of the senses: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eye, trophic changes in the cornea, exophthalmos, sudden loss of vision (with parenteral use in the head, neck, nasal concha, scalp, it is possible to deposit drug crystals in the vessels of the eye).

From the side of metabolism: increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Due to mineralocorticoid activity-fluid and sodium retention (peripheral edema), hypoxia, hypokalemia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system: slowing of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, steroid myopathy, decreased muscle mass (atrophy).

From the skin and mucous membranes: delayed wound healing, petechiae, ecchymosis, skin thinning, hyper-or hypopigmentation, steroid acne, striae, a tendency to develop pyoderma and candidiasis.

Allergic reactions: skin rash, pruritus, anaphylactic shock, local allergic reactions.

Local with parenteral use: burning, numbness, pain, tingling at the injection site, infections at the injection site, rarely-necrosis of surrounding tissues, scarring at the injection site; atrophy of the skin and subcutaneous tissue during intravenous use (especially dangerous introduction to the deltoid muscle).

Other services: the development or exacerbation of infections (the appearance of this side effect is promoted by jointly used immunosuppressants and vaccination), leukocyturia, ” hot flashes “of blood to the face, “withdrawal” syndrome.

Interaction

Pharmaceutical incompatibility of dexamethasone with other intravenous drugs is possible – it is recommended to administer it separately from other drugs (intravenous bolus, or through another dropper, as a second solution). When dexamethasone solution is mixed with heparin, a precipitate is formed.

Concomitant use of dexamethasone with:

• inducers of hepatic microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) leads to a decrease in its concentration;
• diuretics (especially thiazide and carbonic anhydrase inhibitors) and amphotericin B – can lead to increased excretion of K+ from the body and increase the risk of heart failure;
• with sodium-containing drugs – to the development of edema and increased blood pressure;
• cardiac glycosides-their tolerance worsens and the likelihood of developing ventricular extrasitol increases (due to hypokalemia caused);
• indirect anticoagulants-weakens (less often increases) their effects (dose adjustment is required);
• with thrombolytic drugs, and anticoagulants increases the risk of bleeding from ulcers in the gastrointestinal tract;
• ethanol and NSAIDs increases the risk of erosive-ulcerative lesions in the gastrointestinal tract and the development of hemorrhage (in combination with NSAIDs in the treatment of arthritis may reduce the dose of corticosteroids due to summation of therapeutic effect);
• with paracetamol – increased risk of hepatotoxicity (induction of hepatic enzymes and formation of a toxic metabolite of paracetamol);
• acetylsalicylic acid – accelerates its excretion and reduces the concentration in the blood (the abolition of dexamethasone levels of salicylates in the blood increases, and increases the risk of side effects);
• with insulin and paralysie hypoglycemic drugs, antihypertensives decreases their effectiveness;
• vitamin D decreases its effect on the absorption of CA 2+ in the intestine;
• somatotropic hormone reduces the effectiveness of the latter, and with praziquantel – its concentration;
• M-anticholinergics (including antihistamines, and tricyclic antidepressants) and nitrates-increases intraocular pressure;
• isoniazid and mexiletine-increases their metabolism (especially in “slow” acetylators), which leads to a decrease in their plasma concentrations.

Carbonic anhydrase inhibitors and loop diuretics may increase the risk of developing osteoporosis.

Indometacin, by displacing dexamethasone from the albumin bond, increases the risk of side effects.

ACTH enhances the effect of dexamethasone.

Ergocalciferol and parathyroid hormone inhibit the development of dexamethasone-induced osteopathy.

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

Simultaneous use of androgens and steroid anabolic drugs with dexamethasone contributes to 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.

Mitotan and other adrenal cortical inhibitors may require an increased dose of dexamethasone.

When used concomitantly with live antiviral vaccines and against the background of other types of immunization, it increases the risk of virus activation and the development of infections.

Antipsychotics (neuroleptics) and azathioprine increase the risk of cataracts when dexamethasone is prescribed.

When used concomitantly with antithyroid drugs, dexamethasone clearance decreases, and with thyroid hormones, dexamethasone clearance increases.

How to take, course of use and dosage

The dosage regimen is individual and depends on the indications, the patient’s condition and his response to therapy. The drug is administered intravenously slowly in a jet or drip (in acute and urgent conditions); in / m; local (in a pathological formation) use is also possible. An isotonic sodium chloride solution or 5% dextrose solution should be used to prepare the solution for intravenous drip infusion.

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

Dosage of the drug for children (in / m):

The dose of the drug during replacement therapy (for adrenal insufficiency) is 0.0233 mg / kg of body weight or 0.67 mg/m2 of body surface area, divided into 3 doses, every 3rd day or 0.00776-0.01165 mg/kg of body weight or 0.233 – 0.335 mg/m2 of body surface area daily. For other indications, the recommended dose is 0.02776 to 0.16665 mg / kg of body weight or 0.833 – 5 mg/m2 of body surface area every 12-24 hours.

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

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

Overdose

It is possible to increase the side effects described above.

It is necessary to reduce the dose of Dexamethasone. Treatment is symptomatic.

Functional features

List B. Store at a temperature not exceeding 25°C out of the reach of children. Do not freeze it.

Special instructions

During treatment with Dexamethasone (especially long-term), it is necessary to monitor the oculist, monitor blood pressure and the state of water and electrolyte balance, as well as the picture of peripheral blood and blood glucose levels.

In order to reduce side effects, antacids can be prescribed, and the intake of K+ in the body should also be increased (diet, potassium preparations). Food should be rich in protein, vitamins, with a limited content of fats, carbohydrates and table salt.

The effect of the drug is enhanced in patients with hypothyroidism and cirrhosis of the liver.The drug may increase existing emotional instability or psychotic disorders. If a history of psychosis is indicated, Dexamethasone in high doses is prescribed under strict medical supervision.

It should be used with caution in acute and subacute myocardial infarction – it is possible to spread the focus of necrosis, slow the formation of scar tissue and rupture of the heart muscle.

In stressful situations during maintenance treatment (for example, surgery, trauma, or infectious diseases), the dose of the drug should be adjusted due to the increased need for glucocorticosteroids. Patients should be carefully monitored for one year after the end of long-term Dexamethasone therapy due to the possible development of relative insufficiency of the adrenal cortex in stressful situations.

With sudden withdrawal, especially in the case of previous use of high doses, it is possible to develop a “withdrawal” syndrome (anorexia, nausea, lethargy, generalized musculoskeletal pain, general weakness), as well as an exacerbation of the disease for which Dexamethasone was prescribed.

During treatment with Dexamethasone, vaccination should not be carried out due to a decrease in its effectiveness (immune response).

Prescribing Dexamethasone for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat with antibiotics of bactericidal action.

In children, during long-term treatment with Dexamethasone, careful monitoring of the dynamics of growth and development is necessary. Children who have been in contact with measles or chickenpox patients during treatment are prescribed specific immunoglobulins as a preventive measure.

Due to the weak mineralocorticoid effect, Dexamethasone is used in combination with mineralocorticoids for replacement therapy for adrenal insufficiency.

In patients with diabetes mellitus, blood glucose should be monitored and, if necessary, therapy should be corrected.

X-ray monitoring of the osteoarticular system (images of the spine, hand) is shown.

In patients with latent infectious diseases of the kidneys and urinary tract, Dexamethasone can cause leukocyturia, which may have diagnostic significance.

Dexamethasone increases the content of metabolites of 11-and 17-oxyketokorticosteroids.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Dexamethasone

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection