Methylprednisolonum

General characteristics. Structure:

Active ingredient: 40 mg of Methylprednisolonum in 1 ml of suspension.

The hormonal means rendering glucocorticoid, antiinflammatory, antiallergic, antishock, immunodepressive.

Pharmacological properties:

Pharmacodynamics. Interacts with specific receptors in cell cytoplasm, the formed complex gets into a cell kernel, causes an expression/depression of MRNK and changes education on ribosomes of the proteins mediating cellular effects. The mechanism of antiinflammatory action is caused by increase in products of the lipokortin which are inhibiting a phospholipase of A2 and braking a liberation of arachidonic acid from membrane phospholipids with the subsequent oppression of synthesis of cyclic endoperoxides, leukotrienes, PG, thromboxane, oxyacids. Influences all phases of an inflammation. Stabilizing membranes of lysosomes, reduces an exit of lizosomalny enzymes, hyaluronidase synthesis oppresses, reduces permeability of capillaries and formation of inflammatory exudate, improves microcirculation, oppresses products of lymphokines (Interlaken 1 and 2, gamma interferon) in lymphocytes and macrophages, slows down migration of macrophages, processes of infiltration and granulation, suppresses release by eosinophils of mediators of an inflammation, reduces products of collagen and mucopolysaccharides, activity of fibroblasts.

Antiallergic and immunodepressive effect are caused by decrease in synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine and other biologically active agents, reduction of number of the circulating basophiles, suppression of proliferation of adenoid and connecting tissue, reduction of number of T - and B-lymphocytes, mast cells. Suppresses migration of B-cells and interaction of T - and B-lymphocytes, slows down release of lymphokines and products of immunoglobulins. Reduces sensitivity of effector cells to allergy mediators, antibodyformation oppresses, changes an immune response of an organism.

Renders the expressed effect on a metabolism: reduces synthesis and increases an albuminolysis in muscular tissue, increases synthesis of protein in a liver, synthesis of higher fatty acids and triglycerides, causes redistribution of fat and a hyperglycemia, stimulates a gluconeogenesis, increases the maintenance of a glycogen in a liver and muscles, breaks a mineralization of a bone tissue.

Methylprednisolonum acetate — drug for parenteral administration with slow absorption and long action. The action duration (18–36 h) depends on a way of introduction, solubility, the used dosage form, a dose and a condition of the patient. After introduction in oil of 80 mg of drug its action continues during 12 h, and suppressive action on the level of a plasma cortisone is observed within 17 days.

Pharmacokinetics. At intake it is quickly and completely soaked up from a GIT, generally in proximal department of a small bowel (is twice more, than in distal department). At introduction in oil succinate, more slowly — acetate is quicker soaked up (the beginning of its action through 6-48ch). Methylprednisolonum acetate and sodium Methylprednisolonum succinate are quickly hydrolyzed under the influence of blood serum cholinesterases with formation of free Methylprednisolonum. Linkng of Methylprednisolonum with blood proteins — about 40-90%. Biotransformation occurs in a liver. The main metabolites — 20β-гидроксиметилпреднизолон and 20β-гидрокси-6α-метилпреднизолон. Passes through GEB and a placenta, gets into breast milk. T1/2 makes about 3 h of plasma, T1/2 from an organism is 12–36 h. It is removed in the form of metabolites, generally with urine.

Indications to use:

Methylprednisolonum, Methylprednisolonum acetate and sodium Methylprednisolonum succinate. For system use (parenterally and inside). Endocrine diseases: primary or secondary adrenocortical insufficiency (choice drugs — a hydrocortisone or a cortisone; if necessary synthetic analogs can be applied in combination with mineralokortikoida; special value has addition of mineralokortikoid in pediatric practice), an inborn adrenal struma, not purulent thyroiditis, a hypercalcemia at malignant new growths; rheumatic diseases (as additional therapy at an acute current or an aggravation); collagenoses (aggravation or maintenance therapy), the pseudorheumatism (including juvenile — the maintenance therapy low doses in some cases can be required), an acute rheumatic carditis, a system lupus erythematosus, a system dermatomyositis (polymiositis), psoriasis arthritis, acute gouty arthritis, the posttraumatic osteoarthritis ankylosing a spondylitis, an acute or subacute bursitis, acute nonspecific tendosinovit, a synovitis at an osteoarthritis, an epicondylitis; diseases of respiratory tract: a symptomatic sarcoidosis, Leffler's syndrome which is not giving in to therapy by other means, a berylliosis, the fulminant or disseminated pulmonary tuberculosis in combination with the corresponding antitubercular therapy, aspiration pneumonia; hematologic diseases: idiopathic Werlhof's disease at adults (only in/in introduction, introduction in oil it is contraindicated), secondary thrombocytopenia at adults, the acquired (autoimmune) hemolitic anemia, an eritroblastopeniya, inborn (erythroidal) hypoplastic anemia, an agranulocytosis, oncological diseases: leukoses and lymphoma at adults, acute leukoses at children, a myeloma, lung cancer (in a combination with cytostatics); an edematous syndrome (for stimulation of a diuresis or achievement of regression of a proteinuria at patients with a nephrotic syndrome without uraemia, idiopathic type, or caused by a system lupus erythematosus); gastrointestinal diseases (for removal of the patient from a critical state): ulcer colitis, disease Krone, local enteritis, hepatitis; neurologic diseases: exacerbation of multiple sclerosis; myasthenia; tubercular meningitis with the subarachnoidal block or at its threat (in combination with the corresponding antitubercular chemotherapy); trichinosis with defeat of a nervous system or a myocardium; suppression of immunological incompatibility at organ transplantation; nausea and vomiting when performing cytostatic therapy; skin diseases: a pemphigus, violent herpetiform dermatitis, Stephens's syndrome — Johnson, exfoliative dermatitis, mycoses, psoriasis, seborrheal dermatitis; allergic states (serious conditions at which usual therapy is inefficient): seasonal or year-round allergic rhinitis, a serum disease, bronchial asthma, hypersensitivity reactions to medicines, contact dermatitis, atopic dermatitis; anaphylactic and anaphylactoid reactions; eye diseases (heavy acute and chronic allergic and inflammatory processes with damage of eyes): allergic helcomas, ophthalmia, the caused herpes zoster, an inflammation of a front segment, a diffusion back uveitis and a choroiditis, a sympathetic ophthalmia, allergic conjunctivitis, a keratitis, a chorioretinitis, an optic neuritis, an iritis and an iridocyclitis.

For Methylprednisolonum of acetate and Methylprednisolonum of sodium of succinate dopolnitelno:ostry adrenal insufficiency (there can be a need for addition of mineralokortikoid); posttransfusion reactions like small tortoiseshell; acute noninfectious hypostasis of a throat (choice drug — Epinephrinum).

For succinate sodium Methylprednisolonum in addition: acute states at which the bystry hormonal effect of the maximum intensity, including the shock which is a consequence of adrenal insufficiency or shock, resistant to therapy is required by usual methods when existence of adrenal insufficiency is possible (including anaphylactic, burn, traumatic, cardiogenic); in the preoperative period, in case of a severe injury or a serious illness, at patients with the established or suspected adrenal insufficiency; brain hypostasis, acute traumatic injuries of a spinal cord (treatment should be begun in the first 8 h after an injury).

For intra joint, periartikulyarny, intrabursalny use or introduction to soft tissues (water suspension of Methylprednisolonum of acetate): as auxiliary therapy for short-term use (for removal of the patient from an acute state or at a process aggravation) at the following diseases — a synovitis at an osteoarthrosis, the pseudorheumatism, an acute and subacute bursitis, acute gouty arthritis, an epicondylitis, acute nonspecific tendosinovit, a posttraumatic osteoarthrosis.

For introduction to the pathological center (water suspension of Methylprednisolonum of acetate): keloid cicatrixes and the localized inflammation centers at red flat herpes (Wilson deprive), psoriasis plaques, ring-shaped granulomas, simple chronic herpes (neurodermatitis limited), a diskoidny lupus erythematosus, a diabetic lipodystrophy, gnezdny baldness; cystous tumors of an aponeurosis and sinews.

For instillation in a rectum (water suspension of Methylprednisolonum of acetate): ulcer colitis.

Route of administration and doses:

Inside, injektsionno (in/in, in oil, epiduralno, in synovial bags and vaginas, in a cavity of joints, in the field of skin damages) and rektalno. The way of introduction and the mode of dosing are selected individually depending on character and disease severity, age and a condition of the patient, the response to the carried-out treatment.

Inside, adult: 4–60 mg/days once or in the divided doses; usually initial dose — 4–48 mg/days, in some cases — to 100 mg/days; a maintenance dose — 4–12 mg/days. To children: at insufficiency of adrenal glands in 0,14 mg/kg or 4 mg/sq.m  a day in 3 receptions, in oil — the same dose in two days or 0,039–0,0585 mg/kg/days daily; according to other indications — in 0,417–1,67 mg/kg or 12,5–50 mg/sq.m  in three divided doses, in oil — 0,139–0,835 mg/kg or 4,16–25 mg/sq.m  each 12–24 h.

In oil, in the form of suspension (depot form) adult: 40–120 mg during 1–4 weeks.

If at a disease to which therapy is directed also stress symptoms develop, the dose of suspension should be increased. If it is required to gain bystry and maximum effect of hormonal therapy, it is shown in/in introduction of a dosage form with high degree of solubility — sodium Methylprednisolonum succinate.

Enter 30 mg/kg of Methylprednisolonum of succinate within 30 min. into ("pulse therapy"), if necessary — repeatedly each 6 h.

Vnutrisustavno, in synovial bags and vaginas — 20–60 mg, in an abdominal and pleural cavity — to 100 mg, epiduralno — to 80 mg, in/in — 100–500 mg, in the field of skin damages — 20–60 mg.

With the holding enema at ulcer colitis enter 40–120 mg, for stopping of nausea and vomiting: the adult — in a dose of 250 mg in 20 min. prior to and in 6 h after reception of tsitostatik, to children — not less than 25 mg/days.

At approach of spontaneous remission treatment stops.

Features of use:

Use of corticosteroids during pregnancy is possible if the expected effect of therapy exceeds potential risk for a fruit (adequate and strictly controlled researches of safety of use were not conducted). Women of childbearing age need to be warned about potential risk for a fruit (corticosteroids pass through a placenta). It is necessary to watch newborns whose mothers during pregnancy received corticosteroids (possibly development of insufficiency of adrenal glands in a fruit and the newborn) carefully. It is not necessary to use often, in high doses, throughout a long span.

Category of action on a fruit on FDA — C. The feeding women are recommended to stop either breastfeeding, or use of HP, especially in high doses (corticosteroids get into breast milk and can oppress development of endogenous corticosteroids, suppress growth and cause undesirable effects in posterity).

As therapy complications glucocorticoids depend on the size of the applied dose and duration of treatment, in each case it is necessary to compare a ratio risk/advantage for making decision on therapy by glucocorticoids, the mode of dosing, treatment duration. After treatment corticosteroids observed increase in the ALT, nuclear Heating Plant and ShchF level in blood serum. Usually these changes are insignificant, are not connected with any clinical syndromes and are reversible after the treatment termination. The prolonged use of glucocorticoids can lead to development of a back subkapsulyarny cataract, glaucoma with possible injury of an optic nerve, increase in frequency of developing of consecutive viral or fungal infections of eyes is possible. At parenteral use of corticosteroids development of an acute myopathy is possible, and it is the most frequent — at use of high doses of glucocorticoids for patients with neuromuscular transmission disturbance (for example at gravis myasthenia) or at the patients who are at the same time receiving peripheral muscle relaxants (for example a pankuroniya bromide). Such acute myopathy has generalized character, can affect muscles of an eye and respiratory system, lead to development of tetraparesis. Increase in level of a creatine kinase is possible. At the same time clinical improvement or recovery after cancellation of corticosteroids can happen only in many weeks or even in several years. It is necessary to apply the lowest dose of drug providing sufficient therapeutic effect. It is necessary to graduate, gradually reducing a dose. Not to enter depot form in the unrecommended ways (including in/in). At prolonged use it is necessary to control function гипоталамо - pituitary and adrenal system, glucose level in blood serum, to conduct ophthalmologic researches.

It is not recommended to enter into a deltoid muscle. At boiled and smoked and introduction in oil it is necessary to change places of an injection. Intra joint applications carry out not more often than 1 time to 3 weeks.

It is necessary to consider that benzyl alcohol as a part of some dosage forms of Methylprednisolonum of sodium of succinate and acetate is potentially dangerous at topical administration to nervous tissue.

Can promote distribution or accession of the infections caused by viruses, mushrooms, protozoa and parasites (worms). Danger of these complications increases at increase in a dose or a combination of Methylprednisolonum to other immunodepressants.

The patients accepting immunodepressive doses of Methylprednisolonum have to be warned about danger of contact with patients with chicken pox and measles.

At children in a growth period glucocorticoids should be applied only according to absolute indications and on especially careful observation of the doctor. At prolonged use at children growth delay is possible.

Cancellation can be followed by abdominal pains and joints, weakness, nausea, a headache, dizziness, fervescence, appetite loss, decrease in body weight.

At prolonged use it is necessary to reduce food caloric content, to increase potassium consumption, to reduce — sodium. It is better to carry out calculation of a dose at children not on the body weight (kg), and on the surface area (sq.m). Dosage forms for injections are not recommended to be mixed with other injection solutions.

Side effects:

Frequency of development and expressiveness of side effects depend on duration of use and size of the used dose.

System effects.

From endocrine system: an Icenco-Cushing syndrome, an atrophy of bark of adrenal glands, gipotalamo-pituitary insufficiency (especially during stressful situations, such as a disease, an injury, surgical intervention), decrease in tolerance to carbohydrates, steroid diabetes, increase in need for insulin or peroral hypoglycemic HP at patients with a diabetes mellitus, a glucosuria, disturbance of a menstrual cycle, a hirsutism, impotence, a growth inhibition at children.

From a metabolism: negative nitrogenous balance, delay of sodium and water, hypostases, potassium loss, gipokaliyemichesky alkalosis, increase in body weight.

From bodies of a GIT: a round ulcer with possible perforation and bleeding, nausea, vomiting, an ulcer esophagitis, pancreatitis, abdominal distention.

From a nervous system and sense bodys: headache, dizziness, increase in intracranial pressure, brain pseudoneoplasm, mental disorders, spasms, increase in intraocular pressure, exophthalmos.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): arterial hypertension, congestive heart failure (at predisposed patients), arrhythmia, a thrombophilia. There are messages on disturbances of a heart rhythm and/or development of vascular insufficiency and/or a cardiac standstill after succinate sodium Methylprednisolonum, bystry in/in introductions of high doses (introduction bolee0,5 within less than 10 min.); in time or after introduction of high doses of Methylprednisolonum of sodium of succinate bradycardia was noted (communication with speed and duration of introduction is not established). 

From a musculoskeletal system: muscular weakness, a steroid myopathy, decrease in muscle bulk, osteoporosis (especially at women and children); ruptures of sinews, first of all akhillova; compression fractures of vertebras, aseptic necrosis of a head humeral and femur, pathological fractures of long bones.

From integuments: thinning and an atrophy of epidermis, a derma and hypodermic cellulose, deterioration in regeneration, slow healing of wounds, petechias, striya, steroid acnes, a pyoderma, candidiasis, hypo - and a hyperpegmentation, an ecchymoma,

Allergic reactions: small tortoiseshell, acute anaphylaxis, bronchospasm.

Others: decrease in resistance to infectious diseases; reactions in an injection site: burning, numbness, pain, paresthesia and an infection in an injection site, hyper - or hypopigmentation, formation of hems in the place of an injection; atrophy of skin and hypodermic cellulose, sterile abscess.

Interaction with other medicines:

Combined use of Methylprednisolonum and cyclosporine causes mutual braking of metabolism and increase in probability of development of side effects (at combined use of Methylprednisolonum and cyclosporine cases of developing of spasms were noted).

Phenobarbital, дифенгидрамин, Phenytoinum, rifampicin and other inductors of liver enzymes increase the speed of elimination and reduce a therapeutic effectiveness (correction of a dose can be required).

Methylprednisolonum can increase clearance of the acetylsalicylic acid accepted in high doses for a long time that can lead to decrease in its level in blood (at cancellation of Methylprednisolonum the level of acetylsalicylic acid in blood increases and the risk of manifestation of its side effects increases).

It is necessary to apply with care acetylsalicylic acid together with corticosteroids at patients with a prothrombinopenia.

Methylprednisolonum influences effect of peroral anticoagulants: perhaps both strengthening, and reduction of effect of the anticoagulants accepted along with Methylprednisolonum (for maintenance of necessary effect of anticoagulant continuous monitoring of indicators of coagulation is recommended).

The risk of development of a hepatotoxic (induction of liver enzymes and formation of a toxic metabolite of paracetamol) increases in a combination with paracetamol. Action strengthens AKTG.

Alcohol, antacids (slow down absorption), NPVS, including salicylates, phenylbutazone, indometacin increase probability of an ulceration mucous a stomach and bleeding, Amphotericinum In and karboangidraza inhibitors — hypopotassemias, heart failure, osteoporosis, cardiac glycosides — arrhythmias, natriysoderzhashchy drugs — hypostases and hypertensia.

Ergocalciferol and parathormone interfere with the osteopathy caused by Methylprednisolonum.

High doses of Methylprednisolonum reduce efficiency of Somatotropinum.

Reduces activity of peroral antidiabetic means, efficiency of vaccines (live vaccines against the background of Methylprednisolonum can cause a disease).

Mitotanum and other inhibitors of function of bark of adrenal glands can cause need of increase in a dose of Methylprednisolonum.

Contraindications:

Hypersensitivity.

For Methylprednisolonum, Methylprednisolonum of acetate and Methylprednisolonum of sodium of succinate at system use: acute and chronic bacterial or viral diseases, system fungal infections, HIV or AIDS, active and latent tuberculosis (without the corresponding chemotherapy), congestive heart failure, arterial hypertension, recently postponed myocardial infarction (distribution of the center of a necrosis, delay of formation of cicatricial fabric and, thereof, a rupture of a cardiac muscle), a heavy abnormal liver function and/or kidneys, an intestinal anastomosis (in the next anamnesis), an esophagitis, gastritis, an acute or latent round ulcer, a diabetes mellitus, gravis myasthenia, glaucoma, heavy osteoporosis, a hypothyroidism, mental disorders, poliomyelitis (except a bulbar entsefalicheskikh of forms is possible), lymphoma after BTsZh inoculation, the vaccination period.

For acetate Methylprednisolonum suspension: for intra joint use: an artificial joint, disturbance of coagulant system of blood, an intra joint change, periartikulyarny infectious process (including in the anamnesis); in/in and intrathecal introduction.

For some dosage forms of Methylprednisolonum of acetate and Methylprednisolonum of sodium of succinate: (may contain benzyl alcohol which is capable to cause "an asthma syndrome" — gasping syndrome with a lethal outcome): use for premature newborns.

Overdose:

Symptoms: hypostases, emergence of protein in urine, decrease in volume of filtering, arterial hypertension, arrhythmias, a cardiopathy, a hypopotassemia. Repeated frequent use of drug (daily or several times a week) can lead to development of an Icenco-Cushing syndrome for a long time (causes need of the termination of administration of drug).

Treatment: an artificial diuresis, potassium chloride, at a depression and psychoses — a dose decline or drug withdrawal and purpose of fenotiazinovy drugs or salts of lithium (tricyclic antidepressants are not recommended).

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Injection suspension of 40 mg/ml, on 1 ml in each ampoule. On 1, 5 or on 10 ampoules in cardboard packaging.