Megadexan pills 10mg, 60pcs

Composition

Active ingredient:

Dexamethasone 10.0 mg

Auxiliary substances:

Lactose monohydrate (milk sugar) 158.0 mg;

microcrystalline cellulose 20.0 mg;

povidone 5.0 mg;

magnesium stearate 2.0 mg;

croscarmellose sodium 5.0 mg

Pharmacological action

Dexamethasone is a methylated derivative of fluoroprednisolone. It has anti-inflammatory, anti-allergic, desensitizing and immunosuppressive effects.

It interacts with specific cytoplasmic receptors of glucocorticosteroids to form a complex that penetrates the cell nucleus and stimulates the synthesis of matrix ribonucleic acid, the latter induces the formation of proteins, including lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid, and suppresses the synthesis of endoperoxides, prostaglandins, and leukotrienes that contribute to inflammation, allergies, and others.

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

Water-electrolyte exchange:  detains 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, “washes” Ca2+ from the bones, increases the excretion of Ca2+ by the kidneys.

The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; inducing the formation of lipocortin and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; and stabilization of cell membranes and organelle membranes (especially lysosomal ones).

The anti-allergic effect develops as a result of suppressing 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, suppressing the development of lymphoid and connective tissue, reducing the number of T and B lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, and changing the body’s immune response.

In chronic obstructive pulmonary disease, the action is mainly based on inhibiting inflammatory processes, inhibiting the development or prevention of edema of the mucous membranes, inhibiting eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibiting erosion and desquamation of the mucous membrane. Increases the sensitivity of small and medium-sized bronchial beta-adrenergic receptors to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by inhibiting or reducing its production.

The immunosuppressive effect is caused by inhibition of the release of cytokines (interleukin-1 and interleukin-2, interferon gamma) from lymphocytes and macrophages.

Inhibits the synthesis and release of adrenocorticotropic hormone (ACTH) by the pituitary gland and, secondarily, the synthesis of endogenous glucocorticosteroids (corticosteroids). Inhibits the secretion of thyroid-stimulating hormone and follicle-stimulating hormone. It suppresses the release of beta-lipotropin, but does not reduce the content of circulating beta-endorphin.

Increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases the number of red blood cells (by stimulating the production of erythropoietins).

The peculiarity of the action is a significant inhibition of pituitary function and almost complete absence of mineralocorticoid activity. Doses of 1-1.5 mg / day inhibit the adrenal cortex; the biological half-life (T_1/2) is 32-72 hours (the duration of suppression of the hypothalamic-pituitary-adrenal system).

According to the strength of glucocorticosteroid 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.

Pharmacokinetics

After oral use, it is rapidly and completely absorbed, the time to reach the maximum concentration in blood plasma (T_Smax) is 1-2 hours. The relationship with plasma proteins is 77%. Penetrates into the tissue fluid, through the blood-brain and placental barriers.

It is mainly metabolized in the liver, as well as in tissues. Inactive metabolites are mainly excreted by the kidneys in the form of glucuronides and sulfates, a small part — in the form of non-conjugated metabolites and unchanged dexamethasone. 65% of the administered dose is excreted in the first 24 hours by the kidneys. The plasma half-life (T_1/2) is 190 minutes.

Indications

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

Acute and chronic inflammatory diseases of the joints: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, scapular periarthritis, ankylosing spondylitis (Ankylosing spondylitis), juvenile arthritis, Still’s syndrome in adults, bursitis, non-specific tendosynovitis, synovitis and epicondylitis.

Rheumatic fever, acute rheumocarditis.

Bronchial asthma, exacerbation; asthmatic status.

Acute and chronic allergic diseases: allergic reactions to medicines and food, serum sickness, urticaria, allergic rhinitis, angioedema, medicinal exanthema, pollinosis.

Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (with damage to a large surface of the skin), toxidermia, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell’s syndrome), bullous herpetiform dermatitis, malignant exudative erythema (Stevens-Johnson syndrome).

Edema of the brain (including on the background of a brain tumor or associated with surgery, radiation therapy, or head trauma) after preliminary parenteral use.

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

Inflammatory diseases of the eyes: 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 adrenal hyperplasia.

Autoimmune kidney diseases (including acute glomerulonephritis); nephrotic syndrome.

Subacute thyroiditis.

Hematopoietic diseases — agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho-and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.

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

Tuberculosis 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 graft rejection reaction.

Myeloma (in combination with lenalidomide).

Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.

Use during pregnancy and lactation

During pregnancy (especially in the first trimester), the drug can only be used when the expected therapeutic effect exceeds the potential risk to the fetus. With long-term therapy during pregnancy, the possibility of impaired fetal growth is not excluded.

If used 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 breast-feeding should be discontinued.

Contraindications

Hypersensitivity, systemic mycoses, other systemic infections in the absence of adequate antimicrobial therapy, simultaneous use with live antiviral vaccines. Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption. Breast-feeding period.

For short-term use for “vital” indications, the only contraindication is hypersensitivity.

With caution

Systemic parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transmitted, including recent contact with the patient) — herpes simplex, herpes zoster (viremic phase), chickenpox, measles; amoebiasis, strongyloidosis (established or suspected); systemic mycosis; active or latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific antimicrobial therapy.

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 12, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess formation, diverticulitis.

Diseases of the cardiovascular system (CVS), including recent myocardial infarction (in patients with acute and subacute myocardial infarction, necrosis may spread, scar tissue formation may slow down and, as a result, rupture of the heart muscle), decompensated chronic heart failure (CHF), arterial hypertension, hyperlipidemia.

Endocrine diseases — diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Cushing’s disease, and grade III–IV obesity.

Severe chronic renal and / or hepatic insufficiency, nephrourolithiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Liver failure.

Systemic osteoporosis, myasthenia gravis, polio (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 eyes (risk of corneal perforation).

Pregnancy.

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

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

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-type obesity, hirsutism, increased blood pressure (BP), dysmenorrhea, amenorrhea, myasthenia gravis, “steroid” striae), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, “steroid” ulcer of the stomach or duodenum 12, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups. 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 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.

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 visual organ: 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.

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

Due to 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 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), rupture of muscle tendons, “steroid” myopathy, decreased muscle mass (atrophy).

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

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

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

Interaction

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

Accelerates the elimination of acetylsalicylic acid, reduces the content of its metabolites in the blood (when dexamethasone is discontinued, the concentration of salicylates in the blood increases and the risk of side effects increases).

Concomitant use with live antiviral vaccines and other types of immunizations increases the risk of virus activation and infection.

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

Increases the risk of developing hepatotoxic effects of paracetamol (induction of liver enzymes and formation of a toxic metabolite of paracetamol).

Increases (with long-term therapy) the content of folic acid.

Dexamethasone-induced hypokalemia may increase the severity and duration of muscle block with muscle relaxants.

In high doses, it reduces the effect of somatropin.

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

Weakens the effect of vitamin D on the absorption of calcium ions in the intestinal lumen.

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

Reduces the concentration of praziquantel in the blood.

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

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

Nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol increase the risk of ulceration of the gastrointestinal mucosa and bleeding, in combination with NSAIDs for the treatment of arthritis, it is possible to reduce the dose of corticosteroids due to the summation of the therapeutic effect.

Indometacin, by displacing dexamethasone from the albumin bond, increases the risk of 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 (increased metabolic rate). Mitotan and other adrenal cortical inhibitors may require an increased dose of dexamethasone.

Dexamethasone clearance increases with the use of thyroid hormone preparations.

Immunosuppressants increase the risk of developing infections 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 appearance of hirsutism and acne is promoted by the simultaneous use of other steroid hormonal drugs-androgens, estrogens, anabolics, oral contraceptives.

Tricyclic antidepressants may increase the severity of depression caused by dexamethasone (not indicated for the treatment of these side effects).

The risk of developing cataracts increases when used against the background of other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.

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

Concomitant use of antacids reduces dexamethasone absorption.

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

How to take it, course of use and dosage

They are taken orally, in individually selected doses, the value of which is determined by the type of disease, the degree of its activity and the nature of the patient’s response.

Usually, the initial daily dose is from 2 mg to 6 mg. In severe cases, large doses can also be used, divided into 3-4 doses. The maximum daily dose is 10-15 mg. After the therapeutic effect is achieved, 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.

In case of exacerbation of multiple sclerosis, the daily dose can be up to 30 mg during the first week, followed by the use 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 use: 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; 7 day-drug withdrawal.

In case of myeloma in combination with lenalidomide,40 mg of dexamethasone is used once a day on days 1-4,9-12 and 17-20 of each 28-day cycle during the first 4 cycles of therapy, and then 40 mg once a day on days 1-4 of each subsequent 28-day cycle.

Children under 5 years of age are prescribed 0.5-1 mg/day,6-12 years-1-2 mg/day, older than 12 years 2-4 mg/day.

When using a dose of less than 1 mg, dexamethasone,0.5 mg tablets are used.

The duration of use 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.

Dexamethasone test (Liddle test). It is carried out in the form of small and large tests. For a small test, dexamethasone tablets are used in a dose of 0.5 mg.

When performing a large test, dexamethasone is prescribed 2 mg (½tablet of 4 mg) every 6 hours for 2 days (i. e. 8 mg of dexamethasone per day). Urine is also collected to determine 17-ACS or free cortisol (if necessary, determine free cortisol in plasma).

In Itsenko-Cushing’s disease, there is a decrease in the excretion of 17-ACS or free cortisol by 50% or more, while in adrenal tumors or ACTH-ectopic (or corticoliberin-ectopic) syndrome, the excretion of glucocorticosteroids does not change. In some patients with ACTH-ectopic syndrome, reduced corticosteroid excretion is not detected even after taking dexamethasone at a dose of 32 mg / day.

Overdose

The dose-dependent side effects described above may increase. It is necessary to reduce the dose of dexamethasone. Treatment is symptomatic.

Special instructions

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

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 concentration.

In order to reduce side effects, you should increase the intake of potassium in the body (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.

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.

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 11-and 17-OXA.

Influence on the ability to drive vehicles and mechanisms

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

Active ingredient

Dexamethasone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets