Megadexan - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (milk sugar) 80.0 mg; cellulose microcrystalline 10.0 mg; Povidone 2.5 mg; magnesium stearate 1.0 mg; croscarmellose sodium 2.5 mg.

Active substance: dexamethasone 8.0 mg;

Excipients: lactose monohydrate (sugar milk) 160.0 mg; cellulose microcrystalline 20.0 mg; povidone 5.0 mg; magneandI stearate 2.0 mg; croscarmellose sodium 5.0 mg.

Active substance: dexamethasone 10.0 mg;

Excipients: lactose monohydrate (sugar milk) 158.0 mg, microcrystalline cellulose 20.0 mg; povidone 5.0 mg, magnesium stearate 2.0 mg; croscarmellose sodium 5.0 mg.

Description:

Tablets 4 mg and 8 mg: Tablets are round, flat-cylindrical, white or almost white in color, with a risk and a facet.

Tablets 10 mg: Tablets are round, biconcave, white or almost white in color, with a risk.

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:

Dexamethasone is a methylated derivative of fluoride prednisolone. Has anti-inflammatory, antiallergic, desensitizing and immunosuppressive action.

Interacts with specific cytoplasmic receptors of glucocorticosteroids with the formation of a complex that penetrates into the nucleus of the cell and stimulates the synthesis of matrix ribonucleic acid, the latter induces the formation of proteins, including lipocortin, that mediate cellular effects. Lipocortin depresses phospholipase A₂, suppresses the release of arachidonic acid and inhibits the synthesis of endoperoxides, prostaglandins, leukotrienes, which promote inflammation, allergies and others.

Protein metabolism: reduces the amount of protein in the plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumins in the liver and kidneys; 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 (GIT); increases the activity of glucose-6-phosphatase, which leads to an increase in the intake of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, which leads to the activation of gluconeogenesis.

Water-electrolyte exchange: delays sodium (Na⁺) and water in the body, stimulates the excretion of potassium (K⁺) (mineralocorticoid activity), reduces the absorption of calcium (Ca²⁺) from the gastrointestinal tract, "wash out" Sa²⁺ from bones, increases excretion of Ca²⁺ kidneys.

Anti-inflammatory effect is associated with inhibition of eosinophil release by inflammatory mediators; inducing the formation of liportan and reducing the number of mast cells that produce hyaluronic acid; with a decrease in the permeability of capillaries; stabilization of cell membranes and membranes of organelles (especially lysosomal).

Antiallergic effect develops as a result of suppression of synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils histamine and other biologically active substances, a decrease in the number of circulating basophils,inhibition of the development of lymphoid and connective tissue, decrease in the number of T- and B-lymphocytes, mast cells, reduction of the sensitivity of effector cells to mediators of allergy, inhibition of antibody formation, changes in the immune response of the organism.

In chronic obstructive pulmonary disease, the action is mainly based on inhibition of inflammatory processes, inhibition of development or prevention of edema of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the mucous membrane of bronchi, and 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 due to oppression or reduction of its production.

Immunodepressive effect due to inhibition of the release of cytokines (interleukin-1 and interleukin-2, gamma interferon) from lymphocytes and macrophages. Suppresses the synthesis and release of pituitary adrenocorticotropic hormone (ACTT) and the second - the synthesis of endogenous glucocorticosteroids(GCS). Oppressing the secretion of thyroid-stimulating hormone and follicle-stimulating hormone. Suppresses the release of beta-lipotropin, but does not reduce the content of circulating beta-endorphin.

It increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases erythrocytes (by stimulating the production of erythropoietins).

A feature of the action is a significant inhibition of the pituitary function and a virtually complete absence of mineralocorticoid activity.

Doses of 1-1.5 mg / day inhibit the adrenal cortex; biological half-life (T_1/2) - 32-72 h (the duration of oppression of the hypothalamic-pituitary-adrenal system).

The strength of the glucocorticosteroid 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:

After oral intake quickly and completely absorbed, the time to reach the maximum concentration in the blood plasma (TC_mOh) - 1-2 hours. Connection with plasma proteins - 77%. Penetrates into the tissue fluid, through the blood-brain and placental barriers. Metabolized mainly in the liver, as well as in tissues.Inactive metabolites are excreted mainly by kidneys in the form of glucuronides and sulfates, a small part - in the form of unconjugated metabolites and unchanged dexamethasone, 65% of the administered dose is excreted in the first 24 hours by the kidneys. The half-life (T_1/₂) from blood plasma - 190 min.

Indications:

Systemic diseases of connective tissue (systemic lupus erythematosus (SLE), scleroderma, nodular periarteritis, dermatomyositis, rheumatoid arthritis).

Acute and chronic inflammatory joint diseases: gouty and psoriatic arthritis, osteoarthritis (including posttraumatic), polyarthritis, humeropathy periarthritis, ankylosing spondylitis (Bechterew's disease), juvenile arthritis, Still's syndrome in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis .

Rheumatic fever, acute rheumatic heart disease.

Bronchial asthma, exacerbation; asthmatic status.

Acute and chronic allergic diseases: allergic reactions to drugs and foods, whey, urticaria, allergic rhinitis, angioedema, drug exanthema, pollinosis.Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (with damage to the large surface of the skin), toxicermy, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous herpetiform dermatitis, malignant exudative erythema (syndrome Stevens-Johnson).

A cerebral edema (including on the background of a brain tumor or associated with surgery, radiation therapy or head trauma) after previous parenteral administration.

Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.

Inflammatory eye diseases: sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis.

Primary or secondary adrenal insufficiency (including the condition after removal of the adrenal glands).

Congenital hyperplasia of the adrenal glands.

Kidney disease of autoimmune genesis (including acute glomerulonephritis); nephrotic syndrome.

Subacute thyroiditis.

Diseases of the hematopoiesis - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia,acute lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital (erythroid) hypoplastic anemia.

Lung diseases: acute alveolitis, pulmonary fibrosis, sarcoidosis II-III Art.

Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).

Berylliosis, Leffler's syndrome (not amenable to other therapy).

Lung cancer (in combination with cytostatics).

Multiple sclerosis.

Diseases of the gastrointestinal tract: ulcerative colitis, Crohn's disease, local enteritis.

Hepatitis.

Prevention of rejection of graft rejection.

Myeloma (in combination with lenalidomide).

Conduct a sample in the differential diagnosis of hyperplasia (hyperfunction) and adrenal cortex tumors.

Contraindications:

Hypersensitivity, systemic fungal infections, other systemic infections in the absence of adequate antimicrobial therapy, concomitant use with live antiviral vaccines.

Lactose intolerance, lactase deficiency or glucose-galactase malabsorption.

For short-term use according to "vital" indications, the only contraindication is hypersensitivity.

Carefully:

Systemic parasitic and infectious diseases of viral, fungal or bacterial nature (currently or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amoebiasis, strongyloidiasis (or suspected); systemic mycosis; active or latent tuberculosis. Application in severe infectious diseases is permissible only against the background of specific antimicrobial therapy.

The vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.

Immunodeficiency conditions (including AIDS or HIV infection).

Diseases of the gastrointestinal tract: peptic ulcer of the stomach or duodenum, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis.

Diseases of the cardiovascular system (CVS), including the recently transferred myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the necrosis foci, slowing the formation of scar tissuenor and as a result - rupture of the heart muscle), decompensated chronic heart failure (CHF), hypertension, hyperlipidemia.

Endocrine diseases - diabetes (including impaired tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity III-IV degree.

Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Liver failure.

Systemic osteoporosis, myasthenia gravis gravis, poliomyelitis (except for the form of bulbar encephalitis), epilepsy, "steroid" myopathy.

Acute psychosis, severe affective disorders (including in the anamnesis, especially "steroid" psychosis).

Open and closed angle glaucoma, herpes of the eye (risk of corneal perforation).

Pregnancy.

In children during growth dexamethasone It should be used only under absolute indications and under very careful supervision of the attending physician.

Pregnancy and lactation:

During pregnancy (especially in the first trimester) the drug can be applied 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:

Take inside, in individually selected doses, the magnitude of which is determined by the type of disease, the degree of its activity and the nature of the patient's response.

Typically, the initial daily dose is from 2 mg to 6 mg. In severe cases, large doses divided into 3-4 doses may be used. The maximum daily dose is 10-15 mg. After reaching the therapeutic effect, the dose is gradually reduced to a maintenance dose of 2-4 mg / day or more. The minimum effective dose is 0.5-1 mg / day.

With exacerbation of multiple sclerosis the daily dose can be up to 30 mg during the first week followed by application of 4 mg to 12 mg every other day for 1 month.

For the treatment of acute allergic diseases it is advisable to combine parenteral and oral administration: 1 day - 4-8 mg parenterally; 2 day - inside, 4 mg 3 times a day; 3.4 day - inside, 4 mg 2 times a day; 5, 6 day - 4 mg / day, inside; Day 7 - cancellation of the drug.

With myeloma disease in combination with lenalidomide, 40 mg dexamethasone is administered once a day at 1-4, 9-12 and 17-20 days of each 28-day cycle during the first 4 cycles of therapy, and then 40 mg once daily in 1-4 days of each subsequent 28-day cycle.

Children under 5 years appoint 0.5-1 mg / day, 6-12 years old - 1-2 mg / day, over 12 years old - 2-4 mg / day.

When a dose is used, less than 1 mg is used dexamethasone, tablets 0.5 mg. The duration of dexamethasone depends on the nature of the pathological process and the effectiveness of treatment and ranges from several days to several months or more. Treatment is stopped gradually.

Sample with dexamethasone (Liddell test). It is conducted in the form of small and large tests. For a small test, dexamethasone tablets at a dose of 0,5 mg.

When carrying out a large test dexamethasone prescribe 2 mg each (1/2 4 mg tablets) every 6 hours for 2 days (ie 8 mg dexamethasone per day). Urine is also collected to determine 17-ACS or free cortisol (if necessary, determine the free cortisol in the plasma). With Isenko-Cushing's disease, there is a decrease in excretion of 17-ACS or free cortisol by 50% or more, while adrenal gland tumors or ACTH-ectopic (or corticoliberin-ectopic) syndrome do not change the excretion of glucocorticosteroids.In some patients with ACTH-ectopic reduction syndrome, glucocorticosteroids are not detected even after taking dexamethasone at a dose of 32 mg / day.

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 frequency of development and severity of side effects depend on the duration of application, the amount of dose used and the possibility of observing the circadian rhythm of the appointment.

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 adrenal function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, "steroid" stria), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach or duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccough. Increased activity of "liver" transaminases and alkaline phosphatase.

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic 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 side of the organ of vision: 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.

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

Caused by mineralocorticoid activity - fluid retention and sodium ions (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

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

From the skin and mucous membranes: delayed healing of wounds, petechiae, ecchymosis, thinning of the skin, hyper or hypopigmentation, "steroid" acne, "steroid" striae, propensity to develop pyoderma and candidiasis.

Allergic reactions: generalized (skin rash, skin itching, anaphylactic shock).

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

Overdose:

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

Interaction:

Dexamethasone increases the toxicity of cardiac glycosides (because of the resulting hypokalemia, the risk of arrhythmias increases).

Accelerates the removal of acetylsalicylic acid, reduces the content of its metabolites in the blood (with the abolition of dexamethasone, the concentration of salicylates in the blood increases and the risk of side effects increases).

With simultaneous use with live antiviral vaccines and against other types of immunizations, increases the risk of virus activation and the development of infections.

Increases the metabolism of isoniazid, mexiletine (especially in "fast acetylators"), which leads to a decrease in their plasma concentrations.

Increases the risk of hepatotoxic effects of paracetamol (induction of liver enzymes and educationtoxic metabolite of paracetamol).

Increases (with prolonged therapy) the content of folic acid.

Hypokalemia caused by dexamethasone may increase the severity and duration of muscle blockade against the background of muscle relaxants.

In high doses reduces the effect of somatropin.

Dexamethasone reduces the effect of hypoglycemic drugs; enhances the anticoagulant effect of coumarin derivatives.

Weaken the influence of vitamin D on the absorption of calcium ions in the lumen of the intestine. Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by dexamethasone.

Reduces the concentration of praziquantel in the blood.

Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.

Thiazide diuretics, carbonic anhydrase inhibitors, other glucocorticosteroids (GCS), and amphotericin B increase the risk of hypokalemia, sodium-containing drugs - edema and increased blood pressure.

Non-steroidal anti-inflammatory drugs (NSAIDs) and ethanol increase the risk of ulceration of the mucous membrane of the gastrointestinal tract and bleeding, in combination with NSAIDs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect.

Indomethacin, displacing dexamethasone from association with albumin, increases the risk of developing its side effects.

Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis.

The therapeutic effect of dexamethasone decreases under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of microsomal liver enzymes (an increase in metabolic rate).

Mitotane and other inhibitors of the adrenal cortex function may necessitate an increase in the dose of dexamethasone.

The clearance of dexamethasone rises on the background of the use of drugs of thyroid hormones.

Immunosuppressants increase the risk of infection and lymphoma or other lymphoproliferative disorders caused by the Epstein-Barr virus.

Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of dexamethasone, prolong the half-life and their therapeutic and toxic effects.

The emergence of hirsutism and acne is facilitated by the simultaneous use of other steroid hormonal drugs - androgens, estrogens, anabolic, oral contraceptives.

Tricyclic antidepressants can increase the severity of depression caused by dexamethasone (not shown for the therapy of these side effects).

The risk of developing cataracts increases with the use of other SCS, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.

Simultaneous appointment with m-holinoblokatorami (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.

Simultaneous administration of antacids reduces the absorption of dexamethasone.

With simultaneous use with antithyroid drugs is reduced, and with thyroid hormones - increases the clearance of dexamethasone

Special instructions:

Before the beginning of treatment (if it is impossible due to the urgency of the condition - during the treatment), the patient should be examined for possible contraindications. Clinical examination should include examination of the cardiovascular system, radiology examination of the lungs, examination of the stomach and duodenum, urinary system, organ of vision; the control of the formula of blood, the content of glucose and electrolytes in the blood plasma.

During treatment, dexamethasone (especially long) necessary observation oculist, blood pressure control and the state of water-electrolyte balance as well as peripheral blood picture and blood glucose concentrations.

To reduce side effects, you should increase the intake of potassium in the body (diet, potassium preparations). Food should be rich in proteins, vitaminesand, with the restriction of the content of fats, 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.

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 long-term therapy with 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 with dexamethasone, vaccination should not be given 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 prolonged 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.

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-ACS.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, it is necessary to refrain from controlling vehicles and other mechanisms that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 4 mg, 8 mg and 10 mg.

Packaging:

30 tablets are placed in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

100 tablets are placed in a polymer container for medicines.

One container or 2 or 4 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:PL-001969

Date of registration:14.01.2013

Date of cancellation:2018-01-14

The owner of the registration certificate:AGENCY OF RARE MEDICINES AND TECHNOLOGIES, LLC AGENCY OF RARE MEDICINES AND TECHNOLOGIES, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp06.01.2016

Illustrated instructions

Instructions

Megadexan (Megadexan)