Methypredum

General characteristics. Structure:

Active ingredient: 250 mg of Methylprednisolonum in the form of sodium Methylprednisolonum succinate.

Excipients: sodium hydroxide, water for injections.

The synthetic steroid drug having the pharmakodinamichesky properties similar to a hydrocortisone or cortisol at the same time possessing it is considerable big antiinflammatory action while the mineralkortikoidny effect and a hypopotassemia are twice less, than at use of cortisol and hydrocortisone. The diabetogenic effect is insignificant.

Pharmacological properties:

Pharmacodynamics. The effect of Methylprednisolonum, as well as other glucocorticoids, is implemented through interaction with steroid receptors in cytoplasm. Steroidretseptorny the complex is transported in a cell kernel, connects to DNA and changes a transcription of genes for the majority of proteins. Glucocorticoids oppress synthesis of numerous proteins, various enzymes causing destruction of joints (at a pseudorheumatism), and also the cytokines playing an important role in immune and inflammatory responses. Induce synthesis of a lipokortin – key protein of neuroendocrinal interaction of glucocorticoids that leads to reduction of an inflammatory and immune response.

Glucocorticoids, including Methylprednisolonum, suppress or interfere with development of the fabric answer to many thermal, mechanical, chemical, infectious and immunological agents. Thus, glucocorticoids work symptomatic, reducing displays of a disease without impact on the reason. The antiinflammatory effect of Methylprednisolonum at least exceeds efficiency of a hydrocortisone five times.

Endocrine effects of Methylprednisolonum include suppression of secretion of AKTG, inhibition of products of endogenous cortisol, at prolonged use cause a partial atrophy of bark of adrenal glands. Influence metabolism of calcium, vitamin D, carbohydrate, protein and lipidic metabolism therefore at prolonged use of these drugs increase in content of glucose in blood, reduction of density of a bone tissue, the phenomenon of a muscular atrophy and dislipidemiya can be observed. Glucocorticoids also promote increase in blood pressure and modulation of behavior and mood. Methylprednisolonum has practically no mineralokortikoidny activity.

Pharmacokinetics. At intramuscular introduction of Methylprednisolonum the peak of concentration in blood serum is observed in 2 hours, an average elimination half-life – 2-3 hours.

For 77% Methylprednisolonum contacts plasma proteins, communication with transcortinum is insignificant. Distribution volume – 1-1,5 l/kg. Methylprednisolonum is metabolized to inactive metabolites. The specific CYP enzymes providing its transformation are not known. The average clearance makes 6,5 ml/kg/min. Duration of antiinflammatory effect – 18-36 hours. About 5% of drug are removed from an organism with urine.

Indications to use:

The states demanding system or local therapy by glucocorticoids: inflammatory and general rheumatic diseases, autoimmune diseases, allergic states, an acute anaphylaxis, asthma and other diseases of lungs, and also for the purpose of cerebral decompression (for example wet brain against the background of new growths), graft rejection; some dermatological, hematologic, hepatic, neurologic (for example multiple sclerosis, Myasthenia gravis), renal and gastrointestinal diseases (for example nonspecific ulcer colitis, disease Krone).

Methylprednisolonum is also used as an antiemetic in combination with chemotherapy and as a component in schemes of treatment of leukoses, lymphoma and a malignant multiple myeloma.

Route of administration and doses:

Slow intravenous/intramuscular injections or intravenous infusions.

Dosing is individual and depends on a disease and degree of its weight. At shock and after organ transplantation intravenous doses reach to 30 мгкг body weights. High doses (it is higher than 1 mg/kg) intravenously should be entered slowly, within 30-60 minutes. As an antiemetic the patient receiving the cytostatics making sick and vomiting - 250 mg in 20 minutes prior to reception a cytostatics, then, if necessary, intravenously slowly on 250 mg every 6 hours.

For children: on average 1-3 mg/kg of body weight within 24 hours; up to 5 years – 10-20 mg within 24 hours; from 5 to 10 years – 20-40 mg within 24 hours; over 10 years – 40 mg within 24 hours.

For preparation of Methypredum of 250 mg of solution for injections/infusions syringes should add 4,0 ml of sterile water to a bottle with the lyophilized powder. The received solution has to be transparent, without visible impurity.

Features of use:

In order to avoid heavy cardiovascular complications (hypotonia, arrhythmia, bradycardia or an asystolia) high intravenous doses need to be entered slowly. At the first stages intravenous Myasthenia gravis pulse therapy the state can worsen, in rare instances up to the respiratory depression demanding artificial assisted ventilation of lungs. Correction of symptoms begins 2-3 days later with the beginning of therapy.

Corticosteroids have to be applied with care and under medical control by patients with a hypertension, with the congestive heart failure, mental disorders sick with diabetes (or diabetes in the family anamnesis), pancreatitis, with digestive tract diseases (a round ulcer, a local ileitis, ulcer colitis or a diverticulitis with the increased risk of bleeding and perforation), sick osteoporosis, glaucoma and with predisposition to thrombophlebitis. Patients with disturbance of a blood coagulation have to be under medical control.

Glucocorticoids can complicate diagnosis of complications of digestive tract as they cause reduction of a pain syndrome, and also to mask hyper parathyroidism stage of latency.

Methypredum can potentiate ulcerogenic action of salicylates and other non-steroidal anti-inflammatory drugs.

At combined use of Methylprednisolonum and anticoagulants the risk of a gastric ulceration and bleeding increases. Glucocorticoids can also reduce effect of anticoagulants. Thus, the mode of dosing of anticoagulants has to be followed surely by control of a prothrombin time, namely the international normalized index (INI).

Long reception of glucocorticoids suppresses pituitary and adrenal system that leads to development of secondary insufficiency of the kortikoadrenalovy answer which is followed by complications and exacerbations of diseases up to surgical intervention. High doses of Methylprednisolonum considerably reduce risk of development of the listed complications.

Sick hypothyroidism or with a serious illness of a liver because of the increased effect of Methylprednisolonum it is necessary to reduce a dose.

At long reception at children growth delay is possible. Considering it, treatment has to be limited to reception of the minimum doses during the shortest time.

Methylprednisolonum gets through a placenta and is allocated with milk in the period of a lactation.

It is necessary to weigh advantage and risk of reception of Methylprednisolonum during pregnancy.

Glucocorticoids can also increase risk of mortinatality. Newborns from mothers accepting glucocorticoids during pregnancy have to be exposed to careful inspection on existence of signs of a hypnoadrenalism, and also according to indications need for purpose of replacement therapy has to be considered.

It is necessary to avoid feeding by a breast at long system therapy
Methylprednisolonum.

Side effects:

Digestive tract: dyspepsia, increase in appetite, round ulcers with perforation and bleeding, a gullet ulcer, gullet candidiasis, pancreatitis, perforation of a gall bladder.

Musculoskeletal system: proximal myopathy, osteoporosis, rupture of sinews, muscular weakness.

Water and electrolytic balance: a delay of sodium and water in an organism, arterial hypertension, a gipokaliyemichesky alkalosis, a hypopotassemia, chronic heart failure.

Skin: there can be a burning and pain on site of an injection, regeneration delay, a skin atrophy, acne rash.

Endocrine system and metabolism: suppression гипоталамо - pituitary and adrenal function, growth delay, disturbance of a menstrual cycle, an amenorrhea. The cushingoid person, a hirsutism, increase in body weight, decrease in tolerance to carbohydrates, increase in need for insulin and peroral glucose-lowering drugs.

Neuromental sphere: eufobiya, depression, sleeplessness, aggravation of an exacerbation of schizophrenia.

Organs of sight: increase in intraocular pressure, glaucoma, papilledema, cataract, thinning of a cornea and sclera, aggravation of viral and fungus diseases of eyes, exophthalmos.

Immune system: immunosuppression, masking of infections, suppression of reactions to skin tests, hypersensitivity.

The general: opportunistic infections, tuberculosis recurrence, leukocytosis, tendency to thromboembolisms, indisposition.

Drug withdrawal symptoms: fever, mialgiya, arthralgia, adrenal
insufficiency.

Interaction with other medicines:

Antikholinesterazny means: use of corticosteroids and antikholinesterazny means can cause muscular weakness in patients with a myasthenia.

Anticoagulants: at combined use with glucocorticoids strengthening and reduction of effect of anticoagulants can be noted. Parenteral administration of Methylprednisolonum strictly exponentiates thrombolytic action of antagonists of vitamin K (флуиндион, аценокумарол).

Salicylates and other non-steroidal anti-inflammatory drugs: parallel use of salicylates, indometacin and other non-steroidal anti-inflammatory drugs can increase probability of an ulceration of a mucous membrane of a stomach. Methylprednisolonum can promote reduction of level of salicylates in blood serum, increasing their renal clearance.

Hypoglycemic drugs: Methylprednisolonum can partially suppress hypoglycemic effect of peroral antidiabetic means and insulin.

Inductors of enzymes, for example barbiturates, Phenytoinum, Primidonum, carbamazepine, and rifampicin, increase system clearance of Methylprednisolonum, thereby reducing effects of Methylprednisolonum almost twice.

CYP3A4 inhibitors, for example erythromycin, кларитромицин, кетоконазол, итраконазол and тролеандомицин, increase elimination and level of Methylprednisolonum in a blood plasma which can strengthen therapeutic and side effects of Methylprednisolonum.

Estrogen can strengthen effects of Methylprednisolonum, slowing down his metabolism. It is not recommended to regulate Methylprednisolonum doses to the women accepting oral contraceptives which can promote not only increase in an elimination half-life, but also development of atypical immunosuppressive effects of Methylprednisolonum.

Amphotericinum, diuretics and easy purgatives: Methylprednisolonum can increase removal of potassium from an organism at the patients receiving at the same time these drugs.

Immunodepressants: Methylprednisolonum has the additive immunosuppressive properties that can increase therapeutic effects or risk of development of various side reactions at reception together with other immunodepressants. Only some of these effects can be explained with pharmacokinetic interactions. Glucocorticoids improve antiemetic efficiency of other antiemetic drugs used in parallel at therapy by the anticarcinogenic drugs causing vomiting. It was reported about rare attacks of convulsions at parallel reception of Methylprednisolonum and cyclosporine.

Immunization: glucocorticoids can reduce the immunizing efficiency of vaccines and increase risk of neurologic complications. Use of therapeutic (immunosuppressive) doses of glucocorticoids together with live virus vaccines can increase risk of development of viral diseases.

Others: it was reported about two serious cases of an acute myopathy at the elderly patients receiving a doksakarium chloride and Methylprednisolonum in high doses. At long therapy glucocorticoids can reduce effect of Somatotropinum.

Contraindications:

Tuberculosis, and also other acute/persistent bacterial and viral infections at insufficient security of an organism antibiotiko-and chemotherapy.

Overdose:

Methylprednisolonum does not cause acute intoxication. High single doses do not cause seryeznykhpobochny reactions. The antidote of Methylprednisolonum does not exist.

Storage conditions:

To store at the room temperature (15-25 °C) in the unavailable to children, protected from light place. If ready solution is not used directly, it is stored in the refrigerator at a temperature (+2-+8 °C) within 24 hours.

Issue conditions:

According to the recipe

Packaging:

1 bottle with the lyophilized powder and 1 ampoule with solvent in cardboard packaging.