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

Excipients: methylparaben 1.5 mg, propylparaben 0.2 mg, sodium metabisulfite 2.0 mg, disodium edetate 1.0 mg, sodium hydroxide to pH 7.0-8.5, water for injection up to 1 ml.

Description:

A clear solution, colorless or pale yellow.

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, immunosuppressive action, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

Interacts with specific cytoplasmic receptors (receptors for glucocorticosteroids (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).

Protein metabolism: reduces the number of globulins in plasma, increases the synthesis of albumin in the liver and kidneys (with increasing 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 (accumulation of fat occurs mainly in the area 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 Na⁺ and water in the body, stimulates the excretion of K⁺ (mineralocorticoid activity), reduces the absorption of Ca²⁺ from the gastrointestinal tract, reduces the mineralization of bone tissue.

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,producing 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 (lipocortin oppresses phospholipase A₂, suppresses the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, promoting inflammation processes, allergies, etc.), the synthesis of "pro-inflammatory cytokines" (interleukin₁, 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 reduced synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils histamine, etc.biologically active substances, reducing the number of circulating basophils, T- and B-lymphocytes, mast cells; suppression of the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to mediators of allergy, inhibition of antibody formation, changes in the immune response of the body.

In obstructive airway diseases, the effect is mainly due to the inhibition of inflammatory processes, the prevention or reduction of the degree of edema of the mucous membranes, the decrease in the eosinophilic infiltration of the submucosal layer of the bronchial epithelium and the deposition of circulating immune complexes in the bronchial mucosa, as well as the inhibition of erosion and desquamation of the mucosa. 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.

Suppresses the synthesis and secretion of ACTH and, again, the synthesis of endogenous GCS.

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 the pituitary function and a virtually 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 oppression of the hypothalamic-pituitary-cortical adrenal gland system).

The strength of the glucocorticoid activity of 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone, or 17.5 mg of cortisone.

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:

- endokrinnye 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;

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

- asthmatic status; severe bronchospasm (exacerbation of bronchial asthma, chronic obstructive bronchitis);

- severe allergic reactions, anaphylactic shock;

- rheumatic diseases;

- systemic connective tissue diseases;

- acute severe dermatoses;

- Malignant diseases: palliative treatment of leukemia and lymphomas 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;

- severe infectious diseases (in combination with antibiotics);

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

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

Contraindications:

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

In children during the growth period, SCS should be used only in absolute indications and under the strictest supervision of the attending physician.

Carefully:

With the following diseases and conditions:

- diseases of the gastrointestinal tract - peptic ulcer of the stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer,newly created anastomosis of the intestine, ulcerative colitis with perforation or abscessing threat, diverticulitis;

- parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a 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);

- zcardiovascular system abnormalities (including recent myocardial infarction - in patients with acute and subacute myocardial infarction it is possible to spread the focus of necrosis, slow the formation of scar tissue and, as a result, break the heart muscle), severe chronic heart failure, arterial hypertension, hyperlipidemia);

- endocrine diseases - diabetes mellitus (incl.a violation of tolerance to carbohydrates), 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;

- systemic osteoporosis, myasthenia gravis gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma;

- bVariability.

Pregnancy and lactation:

During pregnancy (especially in the first trimester), the drug can be used only when the expected therapeutic effect 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:

Usually Dexamethasone well tolerated. It has a low mineralocorticoid activity, i.e. its effect on water-electrolyte exchange is small. As a rule, low and medium doses of Dexamethasone do not cause delays in sodium and water in the body, increased excretion of potassium.

The following side effects are described:

From the endocrine system: depression of glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, oppression of the adrenal gland function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delay in sexual development in children.

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

From the side of 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.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the sense organs: 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 eyes, trophic changes in the cornea, exophthalmos,sudden loss of vision (when administered parenterally in the head, neck, nasal turbinate, the scalp may be deposited drug crystals in the blood 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 - sodium and fluid retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system: slowing growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - pathological fractures, aseptic necrosis of the humeral head and femur), rupture of tendons of muscles, steroid myopathy, loss of muscle mass (atrophy).

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

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

Local for parenteral administration: burning, numbness, pain, tingling at the injection site, infections at the injection site; rarely - necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with the / m introduction (especially dangerous is the introduction to the deltoid muscle).

Other: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, blood flushing to the face, withdrawal syndrome.

Overdose:

It is possible to strengthen the above described side effects. It is necessary to reduce the dose of Dexamethasone. Treatment is symptomatic.

Interaction:

Possible pharmaceutical incompatibility of dexamethasone with other intravenously administered drugs - it is recommended to inject it separately from other drugs (iv bolus, or through 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, rifampicin, phenytoin, theophylline, 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 K⁺ 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 and the development of bleeding increases (in combination with NSAIDs, a reduction in the dose of glucocorticosteroids due to the summation of the therapeutic effect is possible in the treatment of arthritis);

- paracetamol - increased risk of hepatotoxicity (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 side effects increases);

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

- vitamin D - its effect on the absorption of Ca decreases²⁺ in the intestine;

- Growth 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 mexelitin - 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:

During treatment with Dexamethasone (especially long-term) it is necessary to observe the oculist, control blood pressure and the state of the water-electrolyte balance,as well as pictures 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 (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.

With caution should be used in acute and subacute myocardial infarction - possibly spreading the focus of necrosis, slowing the formation of scar tissue and rupture of the heart muscle.

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.

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

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 metabolites content of 11- and 17-oxyketocorticosteroids.

Form release / dosage:

Solution for injection, 4 mg / ml.

Packaging:

In ampoules of 1 ml or 2 ml.

For 5, 10, 15, 20 or 25 ampoules, together with the instructions for the use of the medicinal product for medical use, are placed in a cardboard pack.

Storage conditions:

At a temperature not higher than 25 ° C, out of the reach of children. Do not freeze.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014442 / 01-2002

Date of registration:18.11.2008

Expiration Date:Unlimited

The owner of the registration certificate:SHREYA LIFE SENENSIZ Pvt.Ltd. SHREYA LIFE SENENSIZ Pvt.Ltd. India

Manufacturer: & nbsp

SHREYA LIFE SCIENCES, Pvt.Ltd. India

Representation: & nbspSHREYA LIFE SENENSIZ Pvt.Ltd. SHREYA LIFE SENENSIZ Pvt.Ltd. India

Information update date: & nbsp21.03.2017

Illustrated instructions

Instructions

Dexamethasone (Dexamethasone)