Metipred, tablets 4 mg 30 pcs

Methylprednisolone is a synthetic glucocorticosteroid drug. It has anti-inflammatory, anti-allergic, immunosuppressive effects, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

It interacts with specific cytoplasmic receptors (all tissues have receptors for glucocorticosteroids (GCS), especially with liver) with the formation of a complex, inducing the formation of proteins (including enzymes regulating cells). Protein metabolism: reduces the number of globulins in the plasma, increases the synthesis of albumin in the liver and kidneys (with an increase in albumin/globulin ratio), reduces synthesis and increases catabolism of protein in muscle tissue.

Lipid metabolism:

increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs primarily in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia

Carbohydrate metabolism:

increases absorption of carbohydrates from the gastrointestinal tract; increases glucose-6-phosphatase activity (increasing glucose entry from the liver into the blood); increases phosphoenolpyruvate carboxylase activity and aminotransferase synthesis (activation of gluconeogenesis); promotes hyperglycemia.

Water-electrolyte metabolism:

retains sodium and water in the body, stimulates potassium excretion (mineralocorticoid activity), reduces the absorption of calcium from the gastrointestinal tract, reduces bone mineralization. Anti-inflammatory effect is connected with inhibition of release of inflammatory mediators by eosinophils and mast cells; induction of formation of lipocortins and reduction of number of mast cells producing hyaluronic acid; reduction of capillary permeability and stabilization of cell membranes (especially lysosomal) and organelle membranes.

It acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A2, inhibits the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, contributing to inflammatory processes, allergies and others).), the synthesis of “pro-inflammatory cytokines” (interleukin 1, tumor necrosis factor alpha, etc.), increases the resistance of the cell membrane to the action of various damaging factors.

The immunosuppressive effect is caused by involution of lymphoid tissue, inhibition of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and interaction between T- and B-lymphocytes, inhibition of cytokine release (interleukin-1, 2 interferon) from lymphocytes and macrophages and decrease of antibody formation.

The anti-allergic effect is developed as a result of decrease of synthesis and secretion of allergy mediators, inhibition of release of histamine and other biologically active substances from sensitized mast cells and basophils. biologically active substances, decrease of the number of circulating basophils, T- and B-lymphocytes, mast cells; suppression of lymphoid and connective tissue development, decrease of sensitivity of effector cells to allergy mediators, suppression of antibody formation, changes in the body’s immune response.

In obstructive respiratory tract diseases the action is caused mainly by inhibition of inflammatory processes, prevention or reduction of mucous membrane edema, decrease of eosinophilic infiltration of submucous layer of bronchial epithelium and deposition of circulating immune complexes in bronchial mucosa and also inhibition of erosion and mucosa desquamation.

It increases sensitivity of beta-adrenoreceptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by reducing its production. Inhibits synthesis and secretion of adrenocorticotropic hormone (ACTH) and secondary to synthesis of endogenous GCS. Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Indications

Systemic connective tissue diseases (SLE, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis);

acute and chronic inflammatory diseases of the joints – gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis (including senile), glenohumeral periarthritis, ankylosing spondylitis (Bechterew’s disease), juvenile arthritis, Still’s syndrome in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis; acute rheumatism, rheumatic carditis, minor chorea;

bronchial asthma, status asthmaticus;

acute and chronic allergic diseases (including allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, Quincke’s edema, drug exanthema, hay fever);

skin diseases – pemphigus, psoriasis, eczema, atopic dermatitis (common neurodermatitis), contractile dermatitis (affecting a large surface of the skin), toxicerma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell’s syndrome), bullous dermatitis herpetiformis, Stevens-Johnson syndrome; cerebral edema (including against the background of a brain tumor or associated with surgery, radiation therapy or head injury) after preliminary parenteral use of GCS;

allergic eye diseases – 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 adrenal hyperplasia; kidney diseases of autoimmune origin (including acute glomerulonephritis);

nephrotic syndrome;

subacute thyroiditis; diseases of the blood and hematopoietic system – agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia;

interstitial lung diseases – acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis;

tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy); berylliosis, Loeffler’s syndrome (not amenable to other therapy);

lung cancer (in combination with cytostatics); multiple sclerosis;

ulcerative colitis, Crohn’s disease, local enteritis;

hepatitis;

hypoglycemic conditions;

prevention of graft rejection during organ transplantation; hypercalcemia due to cancer, nausea and vomiting during cytostatic therapy; multiple myeloma.

Pharmacological effect

Methylprednisolone is a synthetic glucocorticosteroid drug. It has anti-inflammatory, antiallergic, immunosuppressive effects, increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines.

Interacts with specific cytoplasmic receptors (receptors for glucocorticosteroids (GCS) are present in all tissues, especially in the liver) to form a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells.) Protein metabolism: reduces the amount of globulins in plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin/globulin ratio), reduces synthesis and enhances 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; increases the activity of glucose-6-phosphatase (increasing the flow 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 metabolism:

retains sodium and water in the body, stimulates the excretion of potassium (mineralocorticoid activity), reduces the absorption of calcium from the gastrointestinal tract, and reduces bone mineralization. The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils and mast cells; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes (especially lysosomal) and organelle membranes.

Acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A2, suppresses the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, which contribute to the processes of inflammation, allergies, etc.), the synthesis of “proinflammatory cytokines” (interleukin 1, tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.

The immunosuppressive effect is caused by the involution of lymphoid tissue, inhibition of the proliferation of lymphocytes (especially T-lymphocytes), suppression of the migration of B cells and the interaction of T and B lymphocytes, inhibition of the release of cytokines (interleukin-1, 2; interferon gamma) from lymphocytes and macrophages and a decrease in the formation of antibodies.

The antiallergic effect develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, T- and B-lymphocytes, mast cells; suppressing the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, changing the body’s immune response.

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

Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production. Suppresses the synthesis and secretion of adrenocorticotropic hormone (ACTH) and secondarily the synthesis of endogenous GCS. Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Special instructions

The prepared solution for parenteral administration should be stored at a temperature of 15° to 20°C and used within 12 hours. If the prepared solution is stored in the refrigerator at a temperature of 2° to 8°C, it can be used within 24 hours.

During treatment with Metipred (especially long-term), observation by an ophthalmologist, monitoring of blood pressure, water and electrolyte balance, as well as peripheral blood patterns and blood glucose concentrations are necessary. In order to reduce side effects, antacids can be prescribed, as well as increasing the intake of potassium in the body (diet, potassium supplements).

Food should be rich in proteins, vitamins, and limit 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 worsen existing emotional instability or psychotic disorders.

If a history of psychosis is indicated, Metypred is prescribed in high doses under the strict supervision of a physician. It should be used with caution in acute and subacute myocardial infarction due to the possibility of spreading necrosis, slowing down the formation of scar tissue and rupture of the heart muscle.

In stressful situations during maintenance treatment (including surgery, trauma, infectious diseases), the dose of the drug should be adjusted due to the increased need for GCS. With sudden withdrawal, especially in the case of previous use of high doses, withdrawal syndrome may develop (anorexia, nausea, lethargy, generalized musculoskeletal pain, general weakness), as well as an exacerbation of the disease for which Metipred was prescribed.

During treatment with Metipred, vaccination should not be carried out due to a decrease in the immune response and, as a result, a decrease in the effectiveness of the vaccine. When prescribing Metypred for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat with bactericidal antibiotics.

In children, during long-term treatment with Metipred, careful monitoring of the dynamics of growth and development is necessary. Children who during the treatment period were in contact with patients with measles or chickenpox are prescribed specific immunoglobulins prophylactically. Due to the weak mineralocorticoid effect, Metypred is used in combination with mineralocorticoids for replacement therapy for adrenal insufficiency.

In patients with diabetes mellitus, the concentration of glucose in the blood should be monitored and, if necessary, the dose of hypoglycemic agents should be adjusted. X-ray monitoring of the osteoarticular system (images of the spine, hand) is indicated. Metypred can cause leukocyturia in patients with latent infectious diseases of the kidneys and urinary tract, which may have diagnostic value. Metipred increases the content of 11- and 17-hydroxyketocorticosteroid metabolites.

Active ingredient

Methylprednisolone

Composition

Pills. 1 tab.:

– methylprednisolone 4 or 16 mg;

excipients:

lactose monohydrate,

corn starch,

magnesium stearate,

gelatin,

talc,

purified water.

Contraindications

For short-term use for health reasons, the only contraindication is hypersensitivity to methylprednisolone or the components of the drug.

In children during the growth period, GCS should be used only for absolute indications and with careful medical supervision.

The drug should be prescribed with caution for the following diseases and conditions: gastrointestinal diseases – peptic ulcer of the stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with threat of perforation or abscess formation, diverticulitis; parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently suffered, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), chicken pox, measles, amoebiasis, strongyloidiasis, systemic mycosis; active and latent tuberculosis (use for 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); diseases of the cardiovascular system (including recent myocardial infarction – in patients with acute and subacute myocardial infarction, the necrosis focus may spread, slowing down the formation of scar tissue and, as a result, rupture of the heart muscle), severe chronic heart failure, arterial hypertension, hyperlipidemia; endocrine diseases – diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Kyshing disease, obesity (III-IV degrees); severe chronic renal and/or liver failure, nephrourolithiasis; hypoalbuminemia and conditions predisposing to its occurrence; systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open- and closed-angle glaucoma; pregnancy.

Side Effects

From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus, manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (moon-shaped face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, stretch marks), delayed sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding, perforation of the gastrointestinal tract wall, loss of appetite, indigestion, flatulence, hiccups; rarely – increased activity of liver transaminases and alkaline phosphatase.

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

From the central nervous system and peripheral nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness, anxiety, insomnia, dizziness, vertigo, pseudotumor of the cerebellum, headache, convulsions.

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

From the metabolic side: increased excretion of calcium, hypocalcemia, increased body weight, negative nitrogen balance (increased protein breakdown), increased sweating; caused by mineralocorticoid activity – fluid and sodium retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system: slower growth and ossification processes in children (premature closure of the 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).

Dermatological reactions: delayed wound healing, petechiae, ecchymosis, skin thinning, hyper- or hypopigmentation, steroid acne, stretch marks, tendency to develop pyoderma and candidiasis.

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

Local reactions during parenteral administration: burning, numbness, pain, tingling at the injection site, infection of the injection site; rarely – necrosis of surrounding tissues, scar formation at the injection site, atrophy of the skin and subcutaneous tissue with intramuscular injection (injection into the deltoid muscle is especially dangerous).

Other: development or exacerbation of infections (the appearance of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome, “flushes” of blood to the head.

Interaction

Simultaneous administration of methylprednisolone: ​​with inducers of hepatic microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) leads to a decrease in its concentration (increase in metabolic rate); with diuretics (especially thiazide-like and carbonic anhydrase inhibitors) and amphotericin B leads to increased excretion of potassium from the body and an increased risk of developing heart failure;

carbonic anhydrase inhibitors and loop diuretics may increase the risk of osteoporosis;

with sodium-containing drugs promotes the development of edema and increased blood pressure;

with cardiac glycosides leads to a deterioration in their tolerability and an increased likelihood of developing ventricular extrasytolia (due to caused hypokalemia);

with indirect anticoagulants helps to weaken (less often strengthen) their effect (dose adjustment required); with anticoagulants and thrombolytics leads to an increased risk of bleeding from ulcers in the gastrointestinal tract;

with ethanol and NSAIDs increases the risk of erosive and ulcerative lesions in the gastrointestinal tract and the development of bleeding (in combination with NSAIDs in the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect);

with indomethacin increases the risk of developing side effects of methylprednisolone (indomethacin displaces methylprednisolone from association with albumin); with paracetamol increases the risk of hepatotoxicity (induction of liver enzymes and the formation of a toxic metabolite of paracetamol);

with acetylsalicylic acid accelerates its elimination and reduces its concentration in the blood (when methylprednisolone is discontinued, the level of salicylates in the blood increases and the risk of side effects increases);

with insulin and oral hypoglycemic drugs, antihypertensive drugs, their effectiveness decreases; with vitamin D, its effect on calcium absorption in the intestine is reduced;

with HGH, the effectiveness of the latter decreases;

with praziquantel reduces the concentration of the latter;

with m-anticholinergics (including antihistamines and tricyclic antidepressants) and nitrates increases intraocular pressure; with isoniazid and mexiletine increases their metabolism (especially in “slow” acetylators), which leads to a decrease in their plasma concentrations.

ACTH enhances the effect of methylprednisolone. Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by methylprednisolone. Cyclosporine and ketoconazole, by slowing down the metabolism of methylprednisolone, can in some cases increase its toxicity.

The simultaneous administration of androgens and steroidal anabolic drugs with methylprednisolone promotes the development of peripheral edema, hirsutism and the appearance of acne. Estrogens and oral contraceptives containing estrogen reduce the clearance of methylprednisolone, which may be accompanied by an increase in the severity of its action.

Mitotane and other inhibitors of adrenal function may necessitate an increase in the dose of methylprednisolone. When used simultaneously with live antiviral vaccines and against the background of other types of immunization, it increases the risk of viral activation and the development of infections. Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus.

Antipsychotics (neuroleptics) and azathioprine increase the risk of developing cataracts when methylprednisolone is prescribed. The simultaneous administration of antacids reduces the absorption of methylprednisolone.

When used simultaneously with antithyroid drugs, the clearance of methylprednisolone decreases and with thyroid hormones increases.

Pharmaceutical interaction

There may be pharmaceutical incompatibility of methylprednisolone with other intravenously administered drugs. It is recommended to administer it separately from other drugs (iv bolus, or through another dropper, as a second solution).

Overdose

Symptoms: the side effects described above may increase.

Treatment: symptomatic. It is necessary to reduce the dose of Metypred.

Storage conditions

At 15–25 °C

Shelf life

5 years

Manufacturer

Orion Corporation, Finland