Methylprednisolone is a synthetic glucocorticosteroid drug. It has anti-inflammatory, anti-allergic, 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 albumin in the liver and kidneys (with an increase in the albumin / globulin ratio), reduces the synthesis and enhances the catabolism of protein in muscle tissue.
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
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.
retains sodium and water in the body, stimulates the excretion of potassium (mineralocorticoid activity), reduces the absorption of calcium from the gastrointestinal tract, reduces bone mineralization. The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils and mast cells; by 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 at 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, which promote inflammation, allergies, etc.), the synthesis of “pro-inflammatory cytokines 1,” tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.
The immunosuppressive effect is due to 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; gamma-interferon) from lymphocytes and macrophages and decreased antibody production.
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, suppressing antibody production, changing the body’s immune response.
In obstructive respiratory diseases, the action is mainly due to the inhibition of inflammatory processes, the prevention or reduction of the severity of edema of the mucous membranes, a decrease in eosinophilic infiltration of the submucous layer of the bronchial epithelium and the 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 the bronchi of small and medium caliber 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. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.
Orion Corporation, Finland
Pills. 1 tab .:
– methylprednisolone 4 or 16 mg;
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), shoulder-scapular periarthritis, ankylosing spondylitis (ankylosing spondylitis), juvenile arthritis, Still’s syndrome in adults, bursitis, nonspecific tendosynovitis, synovitis and epicondylitis; acute rheumatism, rheumatic carditis, chorea minor;
bronchial asthma, asthmatic status;
acute and chronic allergic diseases (including allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, Quincke’s edema, medicinal exanthema, hay fever);
skin diseases – pemphigus, psoriasis, eczema, atopic dermatitis (common neurodermatitis), contractual dermatitis (affecting a large surface of the skin), toxidermia, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell’s syndrome), bullous herpetiform dermatitis, Stevens-Jones syndrome ; cerebral edema (including against the background of a brain tumor or associated with surgery, radiation therapy or head trauma) after prior parenteral administration 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 condition after removal of the adrenal glands);
congenital adrenal hyperplasia; kidney disease of autoimmune genesis (including acute glomerulonephritis);
subacute thyroiditis; diseases of the blood and hematopoietic system – agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, lympho- and myeloid leukemias, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital anemia;
interstitial lung diseases – acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis;
tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy); beryllium disease, Leffler’s syndrome (not amenable to other therapy);
lung cancer (in combination with cytostatics); multiple sclerosis;
ulcerative colitis, Crohn’s disease, local enteritis;
prevention of the graft rejection reaction during organ transplantation; hypercalcemia against the background of cancer, nausea and vomiting during cytostatic therapy; multiple myeloma.
For short-term use for health reasons, the only contraindication is hypersensitivity to methylprednisolone or drug components.
In children during the period of growth, GCS should be used only for absolute indications and under close medical supervision.
The drug should be prescribed with caution in the following diseases and conditions: gastrointestinal diseases – gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, NUC with the threat of perforation or abscess formation, diverticulitis; parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amebiasis, strongyloidosis, 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 spread of the necrosis focus, slowing of the formation of scar tissue and, as a result, rupture of the heart muscle is possible), severe chronic heart failure, arterial hypertension, hyperlipidemia; endocrine diseases – diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Kyshing’s disease, obesity (III-IV degree); severe chronic renal and / or hepatic failure, nephrourolithiasis; hypoalbuminemia and conditions that predispose to its occurrence; systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma; pregnancy.
From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus, manifestation of latent diabetes mellitus, inhibition of adrenal function, Itsenko-Cushing’s syndrome (moon face, pituitary obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness) 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, impaired appetite, indigestion, flatulence, hiccups; rarely – increased activity of hepatic transaminases and alkaline phosphatase.
From the side of the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); in predisposed patients, the development or increase in the severity of heart failure, changes in the ECG, 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 side of 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 shells, scalp, possible deposition of crystals of the drug in the vessels of the eye).
From the side of metabolism: increased calcium excretion, hypocalcemia, increased body weight, negative nitrogen balance (increased protein breakdown), increased sweating; due to 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: growth retardation and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the humerus and femur head), rupture of muscle tendons, steroid myopathy, decreased muscle mass (atrophy).
Dermatological reactions: delayed wound healing, petechiae, ecchymosis, thinning of the skin, hyper- or hypopigmentation, steroid acne, striae, a tendency to develop pyoderma and candidiasis.
Allergic reactions: skin rash, itching, anaphylactic shock, local allergic reactions.
Local reactions with parenteral administration: burning, numbness, pain, tingling at the injection site, infection of the injection site; rarely – necrosis of surrounding tissues, scarring at the injection site, atrophy of the skin and subcutaneous tissue with intramuscular injection (injection into the deltoid muscle is especially dangerous).
Others: the development or exacerbation of infections (the appearance of this side effect is promoted by jointly used immunosuppressants and vaccinations), leukocyturia, withdrawal syndrome, “hot flushes” of blood to the head.
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 heart failure;
carbonic anhydrase inhibitors and loop diuretics may increase the risk of osteoporosis;
with sodium-containing drugs contributes to the development of edema and an increase in blood pressure;
with cardiac glycosides leads to a deterioration in their tolerance and an increase in the likelihood of developing ventricular extrasitolia (due to induced hypokalemia);
with indirect anticoagulants contributes to the weakening (less often strengthening) of their action (dose adjustment is required); with anticoagulants and thrombolytics leads to an increased risk of bleeding from ulcers in the gastrointestinal tract;
with ethanol and NSAIDs contributes to an increase in 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 side effects of methylprednisolone (displacement of methylprednisolone by indomethacin from its 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 excretion and reduces the concentration in the blood (when methylprednisolone is canceled, 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 decreases;
with STH, the effectiveness of the latter decreases;
with praziquantel reduces the concentration of the latter;
with m-anticholinergics (including antihistamines and tricyclic antidepressants) and nitrates helps to increase intraocular pressure; with isoniazid and mexiletin 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, slowing down the metabolism of methylprednisolone, can in some cases increase its toxicity.
The simultaneous administration of androgens and steroid anabolic drugs with methylprednisolone contributes to the development of peripheral edema, hirsutism and acne. Estrogens and oral estrogen-containing contraceptives reduce the clearance of methylprednisolone, which may be accompanied by an increase in the severity of its action.
Mitotan and other inhibitors of adrenal cortex 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 virus activation and the development of infections. Immunosuppressants increase the risk of 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 given. The simultaneous administration of antacids reduces the absorption of methylprednisolone.
With simultaneous use with antithyroid drugs, it decreases, and with thyroid hormones, the clearance of methylprednisolone increases.
Possible pharmaceutical incompatibility of methylprednisolone with other intravenous injected drugs. It is recommended to administer it separately from other drugs (intravenous bolus, or through another dropper, as a second solution).
How to take, course of administration and dosage
Inside, during or immediately after a meal, with a small amount of liquid.
It is recommended to take the entire daily dose of the drug once or twice daily – every other day, taking into account the circadian rhythm of endogenous secretion of GCS in the interval from 6 to 8 am.
The high daily dose can be divided into 2-4 doses, with a larger dose in the morning. The initial dose of the drug can be from 4 to 48 mg of methylprednisolone per day, depending on the nature of the disease.
For less severe illnesses, lower doses are usually sufficient, although higher doses may be required for individual patients.
High doses may be required for diseases and conditions such as multiple sclerosis (200 mg / day), cerebral edema (200-1000 mg / day), and organ transplantation (up to 7 mg / kg / day). If after a sufficient period of time a satisfactory clinical effect is not obtained, the drug should be discontinued and another type of therapy should be prescribed to the patient.
For children, the dose is determined by the doctor taking into account the weight or surface of the body. With adrenal insufficiency – by mouth 0.18 mg / kg or 3.33 mg / m2 per day in 3 divided doses, with other indications – 0.42-1.67 mg / kg or 12.5-50 mg / m2 per day in 3 steps.
With prolonged use of the drug, the daily dose should be reduced gradually. Long-term therapy should not be stopped suddenly!
Symptoms: the side effects described above may increase.
Treatment: symptomatic. It is necessary to reduce the dose of Metypred.
Store the prepared solution for parenteral administration at a temperature of 15 ° to 20 ° C and use it 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 Metypred (especially long-term), it is necessary to observe an ophthalmologist, control blood pressure, the state of water and electrolyte balance, as well as a picture of peripheral blood and blood glucose concentration. In order to reduce side effects, antacids can be prescribed, as well as increase the intake of potassium into the body (diet, potassium preparations).
Food should be rich in proteins, vitamins, with limited content of fats, carbohydrates and table salt. The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis. The drug can exacerbate existing emotional instability or psychotic disturbances.
If a history of psychoses 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 the focus of necrosis, slowing down the formation of scar tissue and rupture of the heart muscle.
In stressful situations during supportive treatment (including surgery, trauma, infectious diseases), the dose of the drug should be adjusted due to the increased need for GCS. With a sudden cancellation, especially in the case of the 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 Metypred was prescribed.
During treatment with Metypred, 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. Prescribing Metypred for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat with antibiotics with bactericidal action.
In children, during long-term treatment with Metypred, careful monitoring of the dynamics of growth and development is necessary. Children who, during the period of treatment, were in contact with patients with measles or chickenpox, are prophylactically prescribed specific immunoglobulins. Due to the weak mineralocorticoid effect for replacement therapy for adrenal insufficiency, Metypred is used in combination with mineralocorticoids.
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 control of the osteoarticular system is shown (images of the spine, hand). Metipred in patients with latent infectious diseases of the kidneys and urinary tract can cause leukocyturia, which may be of diagnostic value. Metipred increases the content of metabolites of 11- and 17-oxyketocorticosteroids.