Megadexan, tablets 10 mg 60 pcs

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 with the formation of a complex, penetrating the cell nucleus and stimulating the synthesis of matrix ribonucleic acid, the latter induces the formation of proteins, including lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and inhibits the synthesis of endoperoxides, prostaglandins, leukotrienes, contributing to the processes of inflammation, allergy and others.

Protein metabolism: reduces the amount of protein in the plasma (at the expense of globulins) with an increase in the albumin/globulin ratio, increases the synthesis of albumin 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 hypercholesterolemia.

Carbohydrate metabolism: increases absorption of carbohydrates from the gastrointestinal tract (GIT); increases the activity of glucose-6-phosphatase, which leads to increased glucose flow from the liver into the blood; increases phosphoenolpyruvate carboxylase activity and aminotransferase synthesis, which leads to activation of gluconeogenesis.

Water-electrolyte metabolism: Retains sodium (Na⁺) and water in the body, stimulates potassium excretion (K⁺) (mineralocorticoid activity), reduces calcium absorption (Ca^>2+) from the gastrointestinal tract, “leaches” Ca²⁺ from the bones, and increases Ca²⁺ excretion by the kidneys.

The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; induction of lipocortin formation and reduction of the number of mast cells producing hyaluronic acid; reduction of capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal).

. Antiallergic effect results from suppression of synthesis and secretion of allergy mediators, inhibition of release of histamine and other bioactive substances from sensitized mast cells and basophils, reduction of number of circulating basophils, suppression of lymphoid and connective tissue development, decrease of T- and B-lymphocytes quantity, decrease of sensitivity of effector cells to allergy mediators, suppression of antibody formation, change of immune response.

In chronic obstructive pulmonary disease the action is mainly based on inhibition of inflammatory processes, inhibition of development or prevention of mucous membrane edema, inhibition of eosinophilic infiltration of submucous layer of bronchial epithelium, deposition of circulating immune complexes in bronchial mucosa and inhibition of mucous membrane erosion and desquamation. It increases sensitivity of beta-adrenoreceptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by inhibiting or reducing its production.

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

Inhibits synthesis and release of adrenocorticotropic hormone (ACTH) by pituitary gland and secondary synthesis of endogenous glucocorticosteroids (GCS). Inhibits the secretion of thyroid hormone and follicle stimulating hormone. Suppresses the release of beta-lipotropin, but does not decrease circulating beta-endorphin.

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

In terms of glucocorticosteroid activity, 0.5 mg of dexamethasone corresponds to about 3.5 mg of prednisone (or prednisolone), 15 mg of hydrocortisone or 17.5 mg of cortisone.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed; time to reach maximum plasma concentration (T_Cmax) is 1-2 hours. Binding to plasma proteins is 77%. It penetrates into the tissue fluid, through the blood-brain barrier and the placental barrier.

Metabolized mainly in the liver and in the tissues. Inactive metabolites are excreted mainly by the kidneys as glucuronides and sulfates, a small portion as unconjugated metabolites and unchanged dexamethasone. 65% of the administered dose is excreted in the first 24 hours by the kidneys. The elimination half-life (T_1/2) from plasma is 190 min.

Indications

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

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

Rheumatic fever, acute rheumatic heart disease.

Bronchial asthma, exacerbation; asthmatic status.

Acute and chronic allergic diseases: allergic reactions to medications and food products, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, pollinosis.

Skin diseases: Vesicles, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (with large skin surface affected), toxiderma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell syndrome), bullous herpetiform dermatitis, malignant exudative erythema (Stevens-Johnson syndrome).

Brain edema (including against the background of a brain tumor or associated with surgery, radiation therapy or head trauma) after prior parenteral administration.

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

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

Primary or secondary adrenal insufficiency (including conditions after adrenal removal).

Congenital adrenal hyperplasia.

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

Subacute thyroiditis.

Diseases of the hematopoietic organs – agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho- and myeloid leukemia, lymphogranulematosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.

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

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

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

Lung cancer (in combination with cytostatics).

Multiple sclerosis.

Gastrointestinal diseases: ulcerative colitis, Crohn’s disease, localized enteritis.

Hepatitis.

Prevention of transplant rejection reaction.

Myeloma disease (in combination with lenalidomide).

The test in the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.

Active ingredient

Composition

Active ingredient:

Dexamethasone 10.0 mg

Excipients:

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.

How to take, the dosage

It is taken orally, in individually adjusted 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.

The usual starting daily dose is 2 mg to 6 mg. In severe cases, larger doses divided into 3-4 doses may also be used. The maximum daily dose is 10-15 mg. After 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 acute exacerbations of multiple sclerosis, the daily dose may be up to 30 mg for the first week followed by 4 mg to 12 mg every other day for 1 month.

To treat acute allergic diseases it is advisable to combine parenteral and oral administration: day 1 – 4-8 mg parenterally; day 2 – orally, 4 mg 3 times a day; day 3, 4 – orally, 4 mg 2 times a day; day 5, 6 – 4 mg/day, orally; day 7 – withdraw the drug.

In myeloma disease in combination with lenalidomide, use 40 mg of dexamethasone once daily 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 daily on days 1-4 of each subsequent 28-day cycle.

In children under 5 years of age 0.5-1 mg/day, 6-12 years of age 1-2 mg/day, over 12 years of age 2-4 mg/day.

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

The duration of dexamethasone use depends on the nature of the pathological process and the effectiveness of treatment and ranges from a few days to several months or more. Treatment is discontinued gradually.

The dexamethasone test (Liddle test). It is carried out as a small and large test. For the small test, 0.5 mg dexamethasone tablets are used.

In the large test, dexamethasone is given at 2 mg (½ tablet, 4 mg) every 6 hr for 2 days (i.e., 8 mg dexamethasone per day). Urine is also collected for determination of 17-OX or free cortisol (free plasma cortisol is determined if necessary).

In Icenko-Cushing’s disease, there is a 50% or greater decrease in 17-OX or free cortisol excretion, whereas in adrenal tumors or ACTH-ectopic (or corticoliberin-ectopic) syndrome, glucocorticosteroid excretion is unchanged. In some patients with ACTH-ectopic syndrome, no decrease in glucocorticosteroid excretion is detected even after administration of dexamethasone at a dose of 32 mg/day.

Interaction

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

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

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

Increases 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 formation of the toxic metabolite of paracetamol).

Enhances (with prolonged therapy) folic acid.

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

In high doses it reduces the effect of somatropin.

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

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

Ergocalciferol and parathormone prevent dexamethasone-induced osteopathy.

Decreases the concentration of praziquantel in the blood.

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

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

Non-steroidal anti-inflammatory drugs (NSAIDs) and ethanol increase risk of gastrointestinal mucosal ulceration and bleeding; in combination with NSAIDs for arthritis, the dose of GCS may decrease due to the combined therapeutic effect.

Indomethacin, by displacing dexamethasone from binding to albumin, increases the risk of its side effects.

Amphotericin B and carboanhydrase inhibitors increase the risk of osteoporosis.

The therapeutic effect of dexamethasone is reduced by phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of microsomal liver enzymes (increased metabolic rate). Mitotane and other inhibitors of adrenal cortex function may necessitate increasing the dose of dexamethasone.

The clearance of dexamethasone is increased with the use of thyroid hormone drugs.

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

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

The occurrence of hirsutism and acne is promoted by the simultaneous use of other steroid hormonal drugs – androgens, estrogens, anabolics, and oral contraceptives.

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

The risk of cataracts is increased when used with other GCS, antipsychotic medications (neuroleptics), carbutamide and azathioprine.

The concomitant use with m-cholinoblockers (including antihistamines, tricyclic antidepressants), nitrates promotes increased intraocular pressure.

The concomitant administration of antacids reduces absorption of dexamethasone.

Concomitant use with antithyroid drugs decreases and with thyroid hormones increases dexamethasone clearance.

Special Instructions

People should be examined for possible contraindications before starting treatment (if this is not possible due to urgency). Clinical examination should include examination of the cardiovascular system, X-ray examination of the lungs, examination of the stomach and duodenum, urinary system, vision; control of blood count, blood glucose and plasma electrolytes content.

During treatment with dexamethasone (especially long-term), monitoring of ophthalmologist, control of BP and water-electrolyte balance, as well as peripheral blood count and blood glucose concentration.

In order to reduce side effects, the intake of potassium in the body should be increased (diet, potassium supplements). Food should be rich in proteins and vitamins, with restriction of fats, carbohydrates and table salt.

The action of the drug is increased in patients with hypothyroidism and cirrhosis. The drug may aggravate 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 (e.g., surgery, trauma, or infectious diseases), the drug dose should be adjusted due to the increased need for glucocorticosteroids. Patients should be closely monitored for one year after completion of long-term dexamethasone therapy due to the possible development of relative insufficiency of the adrenal cortex in stressful situations.

In abrupt withdrawal, especially if high doses were previously used, withdrawal may occur (anorexia, nausea, lethargy, generalized musculoskeletal pain, generalized weakness), and exacerbation of the disease for which dexamethasone was prescribed.

Vaccination should not be performed during treatment with dexamethasone due to decreased effectiveness (immune response).

When dexamethasone is prescribed for intercurrent infections, septic conditions and tuberculosis, bactericidal antibiotics should be treated at the same time.

In children during long-term treatment with dexamethasone, the dynamics of growth and development should be closely monitored. Children who have been in contact with patients with measles or chickenpox during treatment are given specific immunoglobulins prophylactically.

In patients with diabetes, blood glucose levels should be monitored and therapy should be adjusted if necessary.

The bone and joint system (spine, hand films) should be monitored with radiological monitoring.

In patients with latent renal and urinary tract infections, dexamethasone may cause leukocyturia, which may be of diagnostic value.

Dexamethasone increases 11- and 17-OX metabolites.

Impact on driving and operating machinery

At the time of treatment, it is necessary to refrain from driving vehicles and other mechanisms requiring increased concentration and quick psychomotor reactions.

Contraindications

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

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

With caution

Systemic parasitic and infectious diseases of viral, fungal or bacterial nature (current or recent, including recent exposure) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles; amebiasis, strongyloidiasis (established or suspected); systemic mycosis; active or latent tuberculosis. Use in severe infectious diseases is allowed 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).

Gastrointestinal diseases: gastric or 12 duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with risk of perforation or abscesses, diverticulitis.

Diseases of the cardiovascular system (CVD), including recent myocardial infarction (patients with acute and subacute myocardial infarction may have a spread of necrosis, delayed scar tissue formation and, therefore, a rupture of the heart muscle), decompensated chronic heart failure (CHF), arterial hypertension, hyperlipidemia.

Endocrine diseases – diabetes (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Icenko-Cushing’s disease, and obesity of III-IV degree.

Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

Hepatic insufficiency.

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 eye (risk of corneal perforation).

Pregnancy.

In children during growth, dexamethasone should be used only with absolute indications and under the special close supervision of the attending physician.

Side effects

Dexamethasone is usually well tolerated. It has 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 and increased potassium excretion.

The frequency and severity of side effects depend on the duration of use, the amount of dose used, and the ability to follow the circadian rhythm of administration.

The following side effects have been described:

Endocrine system side effects: Decreased glucose tolerance, “steroid” diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Icenko-Cushing’s syndrome (moon-shaped face, pituitary-type obesity, hirsutism, increased blood pressure (BP), dysmenorrhea, amenorrhea, myasthenia, “steroid” stretching), delayed sexual development in children.

In the digestive system: nausea, vomiting, pancreatitis, “steroid” gastric or 12 duodenal ulcer, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups. Increased activity of “hepatic” transaminases and alkaline phosphatase.

Cardiovascular system disorders: arrhythmias, bradycardia (up to cardiac arrest); development (in susceptible patients) or increase of severity of chronic heart failure, electrocardiogram changes typical for hypokalemia, increased BP, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction – expansion of the focus of necrosis, delayed formation of scar tissue, which may 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, cerebellar pseudotum, headache, seizures.

In the organs of vision: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes of the cornea, exophthalmos.

Metabolic disorders: increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

The mineralocorticoid-induced fluid and sodium ion retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

Musculoskeletal system disorders: growth retardation and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the humeral and femoral head), rupture of muscle tendons, “steroid” myopathy, decrease of muscle mass (atrophy).

Skin and mucous membranes: delayed wound healing, petechiae, ecchymoses, skin thinning, hyper- or hypopigmentation, “steroid” acne, “steroid” stretch marks, tendency to develop pyoderma and candidiasis.

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

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

Overdose

Pregnancy use

In pregnancy (especially in the first trimester), the drug may be used only when the expected therapeutic effect exceeds the potential risk to the fetus. During prolonged therapy during pregnancy, the possibility of fetal growth disturbance cannot be excluded.

If used at the end of pregnancy, there is a risk of adrenal atrophy in the fetus, which may require substitution therapy in the newborn.

If treatment with the drug is necessary during breastfeeding, breastfeeding should be stopped.

Similarities