Methylprednisolone

Package leaflet (information for patients)

Tradename
Methylprednisolone

Dosage form
Tablets 4 mg.

Description
Round, flat, beveled to the edge white tablets with an imprint in the form of the brand name "V" on one side.

Structure
Active ingredient: Methylprednisolone 4 mg.
Excipients: microcrystalline cellulose 102, calcium stearate, aerosil ® 200 (hydrophilic pyrogenic silicon dioxide).

Pharmacotherapeutic group
Glucocorticosteroid

Pharmacological properties
Pharmacodynamics
Methylprednisolone is a synthetic glucocorticosteroid. Glucocorticoids penetrate cell membranes and form complexes with specific cytoplasmic receptors that penetrate into the cell nucleus, bind to DNA (chromatin), stimulate mRNA transcription and further synthesis of various enzymes, which explains the effect of systemic use of glucocorticoids.
Methylprednisolone is an analogue of prednisolone. In activity it is close to prednisolone, but practically does not have mineralocorticoid activity, which ensures better tolerability.
Glucocorticoids not only have a significant effect on the inflammatory process and immune response, but also affect carbohydrate, protein and fat metabolism, the cardiovascular system, skeletal muscle and the central nervous system.
Influence on the inflammatory process and the immune response
Methylprednisolone has anti-inflammatory, desensitizing and angiallergic effects. Has anti-shock, anti-toxic and immunosuppressive properties.
Unlike cytostatics, the immunosuppressive properties of methylprednisolone are not associated with mitostatic action, but are the result of suppression of different stages of immunogenesis: migration of bone marrow stem cells, migration of B cells and interaction of T and B lymphocytes.
Like other corticosteroids, methylprednisolone inhibits the release of cytokines (interleukins 1 and 2, γ-interferon) from lymphocytes and macrophages, inhibits the release of inflammatory mediators by eosinophils, reduces the metabolism of arachidonic acid, which achieves the following therapeutic effects: a decrease in the number of immunoactive inflammatory cells; decrease in vasodilation ; stabilization of lysosomal membranes; inhibition of phagocytosis; decrease in the production of prostaglandins and related compounds.
A dose of 4 mg methylprednisolone has the same glucocorticosteroid (anti-inflammatory) effect as 20 mg of hydrocortisone. Methylprednisolone has only a minimal mineralocorticoid effect (200 mg methylprednisolone is equivalent to 1 mg deoxycorticosterone).
Influence on protein and carbohydrate metabolism
Glucocorticoids exhibit a catabolic effect on proteins: they delay and accelerate the breakdown of proteins.
By stimulating steroid receptors, they induce the formation of a special class of proteins - lipocortins, which have a decongestant effect.
The amino acids that are released are converted by gluconeogenesis in the liver to glucose and glycogen.
The absorption of glucose in peripheral tissues is reduced, which can lead to hyperglycemia and glucosuria, especially in patients prone to diabetes mellitus.
Effect on fat metabolism
Glucocorticoids have lipolytic activity, manifested primarily in the tissues of the extremities, and lipogenetic activity, which is most pronounced in the chest, neck and head, which leads to the redistribution of fatty deposits.
In relatively high doses, it inhibits the development of lymphoid and connective tissue, including the reticuloendothelium ; reduces the number of mast cells, which are the site of formation of hyaluronic acid; inhibits the activity of hyaluronidase and helps to reduce capillary permeability.
The maximum pharmacological activity of corticosteroids appears when peak plasma concentrations have already been passed, therefore it is believed that the vast majority of the therapeutic effects of drugs are primarily due to the modification of enzyme activity, and not the direct action of the drug.
Pharmacokinetics
The pharmacokinetics of methylprednisolone is linear, regardless of the route of administration.
Suction
The bioavailability of methylprednisolone in healthy people after ingestion is generally high (82-89%).
After oral administration, methylprednisolone is rapidly absorbed and the maximum concentration of methylprednisolone in blood plasma is achieved within 1.5-2.3 hours (depending on the dose) after taking this drug by healthy people. The absorption rate in the distal region is approximately 50% of the absorption level in the proximal region.
Distribution
Methylprednisolone is widely distributed in tissues, crosses the blood-brain barrier and is excreted in breast milk. Forms weak dissociated bonds with albumin and transcortin.
Plasma protein binding of methylprednisolone in humans is approximately 77%. The volume of distribution of methylprednisolone a is approximately / kg.
Metabolism
Methylprednisolone is metabolized in the liver to inactive metabolites.
The main metabolites are 20-α- hydroxymethylprednisolone and 20-β- hydroxymethylprednisolone.
Its metabolism in the liver occurs mainly with the participation of the CYP3A4 enzyme (for a list of drug interactions based on metabolism mediated by CYP3A isoenzymes, see the section "Interaction with other drugs and other types of interactions"). Conjugation reactions occur mainly in the liver, to a lesser extent in the kidneys.
Withdrawal
Metabolites are excreted mainly in the urine in the form of glucuronides, sulfates and unconjugated compounds.
The half-life of the total amount of methylprednisolone is 1.8 to 5.2 hours. The total clearance is about 5-6 ml / min / kg. Methylprednisolone is excreted by hemodialysis.

Indications for use
Endocrine diseases
Primary and secondary adrenal cortex insufficiency (in this case, the first-line drugs are hydrocortisone or cortisone; if necessary, synthetic analogues can be used in combination with mineralocorticoids ; the simultaneous use of mineralocorticoids is especially important for the treatment of children); congenital adrenal hyperplasia; non-suppurative thyroiditis ; hypercalcemia I in malignant tumors.
Non-endocrine diseases
Rheumatic diseases
As an additional therapy for short-term use (to remove the patient from an acute condition or with an exacerbation of the process) in such diseases:
psoriatic arthritis;
rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases, low-dose maintenance therapy may be required);
ankylosing spondylitis;
acute and subacute bursitis;
acute nonspecific tendosynovitis ;
acute gouty arthritis;
post-traumatic osteoarthritis;
synovitis with osteoarthritis;
epicondylitis.
Collagenoses
During an exacerbation or, in some cases, as maintenance therapy for such diseases:
systemic lupus erythematosus;
acute rheumatic heart disease;
systemic dermatomyositis (polymyositis);
polymyalgia rheumatica with giant cell arteritis.
Skin diseases
Pemphigus;
bullous dermatitis herpetiformis;
severe erythema multiforme (Stevens- Johnson syndrome);
fungal mycosis;
severe forms of psoriasis;
exfoliative dermatitis;
severe seborrheic dermatitis.
Allergic diseases
Control of severe or allergic conditions for which conventional therapy is ineffective:
bronchial asthma;
dermatitis (contact, atopic);
serum sickness;
seasonal or persistent allergic rhinitis;
drug allergy.
Ophthalmic diseases
Severe acute and chronic allergic and inflammatory processes with eye damage, such as:
allergic edge corneal ulcers;
eye lesions caused by Herpes zoster,
inflammation of the anterior segment of the eye;
diffuse posterior uveitis and choroiditis ;
sympathetic ophthalmia;
allergic conjunctivitis;
keratitis;
chorioretinitis ;
iritis and iridocyclitis;
optic neuritis.
Respiratory diseases
Symptomatic sarcoidosis ;
Lefler's syndrome, refractory to therapy with other methods;
beryllium disease ;
focal or disseminated pulmonary tuberculosis (together with appropriate anti-tuberculosis chemotherapy);
aspiration pneumonitis.
Blood diseases
Idiopathic thrombocytopenic purpura in adults;
secondary thrombocytopenia in adults;
acquired (autoimmune) hemolytic anemia;
erythroblastopenia (erythrocytic anemia);
congenital (erythroid) hypoplastic anemia.
Oncological diseases as palliative therapy:
leukemia and lymphoma in adults;
acute leukemia in children.
Edematous syndrome
For the induction of diuresis or the treatment of proteinuria with nephrotic syndrome without uremia, idiopathic type or caused by systemic lupus erythematosus.
Zabo Levan digestive tract
To remove a patient from a critical condition with such diseases:
ulcerative colitis;
Crohn's disease.
Diseases of the nervous system:
multiple sclerosis in the acute phase;
cerebral edema caused by a brain tumor.
Diseases of other organs and systems:
tuberculous meningitis with subarachnoid block or with the threat of block development, in combination with appropriate anti-tuberculosis chemotherapy;
trichinosis with damage to the nervous system or myocardium.
Organ transplant.

Method of administration and dosage
The starting dose for adults can range from 4 to 48 mg of methylprednisolone per day, depending on the indication. The lowest dose of corticosteroids should be used to control the course of the disease.
For less severe medical conditions, low doses are usually sufficient, although higher starting doses may be required in some patients.
High doses can be used for diseases and conditions such as multiple sclerosis (200 mg per day), cerebral edema (200-1000 mg per day), organ transplantation (up to 7 mg / kg per day).
If after an appropriate period of time a satisfactory clinical effect is not achieved, therapy with methylprednisolone tablets should be discontinued and the patient should be prescribed alternative therapy. If, after long-term therapy, the drug needs to be canceled, it is recommended to do it gradually, and not suddenly.
If, as a result of therapy, a satisfactory effect is achieved, the patient should select an individual maintenance dose by gradually decreasing the initial dose at regular intervals until the lowest dose is found that will maintain the achieved clinical effect.
It should be remembered that constant monitoring of the dosage of the drug is necessary. Situations in which it may be necessary to adjust the dose of the drug include: changes in the clinical condition caused by the onset of remission or exacerbation of the disease; individual patient response to the drug; the impact on the patient of stressful situations is not directly related to the underlying disease to which the therapy is directed. In the latter case, it may be necessary to increase the dose of methylprednisolone for a certain period of time, depending on the patient's condition. It should be emphasized that the required dose may vary and should be selected individually, depending on the nature of the disease and the patient's response to therapy.
Alternating therapy (AT)
Alternative therapy is a corticosteroid dosing regimen in which a double dose of glucocorticoids should be given every other day in the morning. The goal of this type of therapy is to maximize the benefits of corticosteroid use in a patient requiring long-term therapy while minimizing some of the unwanted effects, such as suppression of the pituitary-adrenal system, cushingoid state, corticosteroid withdrawal, and growth inhibition in children.

Side effects
The severity and frequency of side effects depend on the dose and duration of use.
Metabolism: sodium and water retention, negative nitrogen balance, edema, hypokalemic alkalosis, loss of potassium, weight gain.
Endocrine system: adrenal cortex atrophy, Itsenko- Cushing's syndrome, hypothalamic-pituitary insufficiency (especially in stressful situations such as trauma, illness, surgery), steroid diabetes, decreased carbohydrate tolerance, increased need for oral hypoglycemic drugs and insulin in patients with diabetes mellitus, menstrual irregularities, impotence, glucosuria, hirsutism, growth retardation in children.
Digestive system: bloating, nausea, peptic ulcer with possible perforation and bleeding, ulcerative esophagitis, vomiting, pancreatitis.
Cardiovascular system and blood (hematopoiesis, hemostasis): congestive heart failure (in predisposed patients), arterial hypertension, thrombophilia, arrhythmia. There are reports of the development of vascular insufficiency and / or cardiac arrhythmias and / or cardiac arrest after rapid intravenous administration of high doses of methylprednisolone sodium succinate (more than 0.5 g was administered within less than 10 minutes); during or after the administration of high doses of methylprednisolone sodium succinate, bradycardia was noted (the relationship with the rate and duration of administration has not been determined).
Nervous system and sensory organs: dizziness, headache, pseudotumor of the brain, increased intracranial pressure, convulsions, mental disorders, increased intraocular pressure, exophthalmos.
Musculoskeletal system: steroid myopathy, muscle weakness, decreased muscle mass, osteoporosis (especially in children and women), compression fractures of the vertebrae, pathological fractures of the long bones, aseptic necrosis of the femoral head and humerus, tendon ruptures, primarily Achilles.
Allergic reactions: anaphylactic shock, urticaria, bronchospasm.
Skin: deterioration of regeneration, atrophy and thinning of the epidermis, subcutaneous tissue, dermis, petechiae, slow wound healing, striae, pyoderma, steroid acne, candidiasis, ecchymosis, hypo - and hyperpigmentation.
Others: decreased resistance to infection.
Reactions at the injection site: numbness, burning, pain, infection at the injection site, paresthesia, scarring at the injection site, hyper- or hypopigmentation, sterile abscess, atrophy of the skin and subcutaneous tissue.

Contraindication
hypersensitivity to methylprednisolone or to other components of the drug;
systemic infections in cases where specific antimicrobial therapy is not intended;
systemic fungal infections;
The administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Overdose
A single dose of the drug that could cause life-threatening symptoms has not been established. The use of exemestane in a single dose of up to 800 mg in healthy women and in a daily dose of up to 600 mg in postmenopausal women with advanced breast cancer was well tolerated. There are no specific antidotes. Treatment is symptomatic, under regular monitoring of vital functions and close supervision.

Precautions
Corticosteroids should be used with caution and under strict medical supervision in patients with arterial hypertension, congestive heart failure, diabetes mellitus (or a family history of diabetes), pancreatitis, and diseases of the digestive tract (peptic ulcer, local ileitis, ulcerative colitis, or other inflammatory diseases of the digestive tract or diverticulitis with an increased risk of bleeding and perforation), eye herpes (as possible perforation of the cornea), hypothyroidism, corticosteroid-induced myopathy in history, liver failure, cirrhosis of the liver, epilepsy, abscess or other pyogenic infections, glaucoma, prone to thrombophlebitis and mentally disorders.
It is also necessary to be careful when prescribing the drug to patients who have recently had myocardial infarction, with recent intestinal anastomoses and renal failure.
Patients with bleeding disorders need to be under medical supervision.
Immunosuppressive Effects / Increased Susceptibility to Infections
Corticosteroids can increase susceptibility to infections and mask some symptoms of infections; in addition, new infections may develop with corticosteroid therapy.
With the use of corticosteroids, resistance to infections may decrease and there may be an inability to localize the infection.
There is a risk of developing secondary infections caused by bacteria, fungi, viruses, protozoa or helminths with any localization in the body, which can occur against the background of the use of corticosteroids as monotherapy or in combination with other immunosuppressive agents that affect the state of cellular and humoral immunity and the function of neutrophils...
These infections can be mild, but sometimes severe and even fatal are possible.
With increasing doses of corticosteroids, the incidence of infectious complications increases.
Patients on drugs that suppress the immune system are more susceptible to infections than healthy people.
Chickenpox and measles, for example, can be more serious or even fatal in unimmunized children or adults who take corticosteroids.
The use of live or live attenuated vaccines to patients who receive corticosteroids immunosupre ssivnyh doses contraindicated.
Patients receiving immunosuppressive doses of corticosteroids can be vaccinated with killed or inactivated vaccines, but their response to such vaccines may be diminished. These immunization procedures may be carried out in patients who receive corticosteroids at doses not okazyvayuschi x immunosuppressive action.
The use of corticosteroids for active tuberculosis should be prescribed only in cases of fulminant or disseminated tuberculosis, when corticosteroids must be used in combination with appropriate anti-tuberculosis therapy. If corticosteroids are indicated for patients with latent tuberculosis or during the bend of tuberculin tests, treatment should be carried out under the strict supervision of a physician, since the process may be reactivated. During long-term corticosteroid therapy, such patients should be prescribed appropriate prophylactic treatment.
Cases of Kaposi 's sarcoma have been reported in patients receiving corticosteroid therapy. In such cases, discontinuation of corticosteroid therapy may lead to clinical remission.
There is no consensus on the role of corticosteroids in the treatment of patients with septic shock.
Previous studies have reported both positive and negative effects of corticosteroid use in this clinical setting.
Later studies showed that corticosteroids as adjunctive therapy had a beneficial effect in patients with septic shock and adrenal insufficiency.
However, the routine use of these drugs is not recommended in patients with septic shock. A systematic review of the data led to the conclusion that there is no beneficial effect of the use of short courses of high doses of corticosteroids in these patients.
However, a meta-analysis and one review have shown that longer (5-11 days) courses of low-dose corticosteroid treatment can reduce mortality, especially in patients with septic shock dependent on vasopressor therapy.
In addition, corticosteroids should be used with great caution in patients with confirmed or suspected parasitic infections, such as strongyloidiasis (acne infection).
In these patients, corticosteroid-induced immunosuppression can lead to strongyloid hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal septicemia caused by gram- negative organisms.
Effects on the immune system
Allergic reactions (eg, angioedema) may occur.
Since, in rare cases, skin reactions and anaphylactic / anaphylactoid reactions have been recorded in patients receiving corticosteroid therapy, appropriate precautions should be taken before use, especially if the patient has a history of allergy to any drug.
Influence on the endocrine system
Patients undergoing corticosteroid therapy and who are exposed to stress are shown to increase the dose of fast-acting corticosteroids before, during and after the stressful situation.
Long-term use of glucocorticoids can lead to suppression of the hypothalamic-pituitary-adrenal system (the development of insufficiency of the secondary adrenal cortex) and contribute to the exacerbation of diseases and the development of complications in various conditions, for example, in acute injuries, diseases, or surgical intervention.
The degree and duration of adrenocortical insufficiency varies from patient to patient and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy.
This effect can be minimized by using alternating therapy (see section "Method of administration and dosage"). High doses of methylprednisolone significantly reduce the risk of developing these complications.
With the sudden withdrawal of glucocorticoids, acute adrenal insufficiency can develop, which can be fatal.
Adrenocortical insufficiency caused by the use of the drug can be minimized by gradually decreasing the dose.
This type of relative deficiency can be recorded for several months after the discontinuation of therapy, therefore, if stressful situations arise during this period, hormone therapy must be restored.
Since the secretion of mineralocorticoids may be impaired, electrolytes and / or mineralocorticoids should be administered simultaneously.
With long-term use of glucocorticoids, therapy should be discontinued gradually over several weeks in order to avoid "withdrawal syndrome" and serious complications. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss, and / or hypotension. These effects are thought to be due to sudden changes in glucocorticoid concentration rather than low corticosteroid levels.
Long-term therapy should not be discontinued abruptly also in case of pregnancy. Because glucocorticosteroids can cause or worsen Cushing's syndrome, patients with Cushing 's disease should avoid using them.
Special attention should be paid to the use of corticosteroids in patients with hypothyroidism, which requires frequent monitoring of their condition. Or hypothyroidism patients with severe liver diseases due to the increased effect metilpre dnizolona be to reduce the dose.
Metabolic and nutritional disorders
Corticosteroids, including methylprednisolone, can increase blood glucose, worsen the condition of patients with a history of diabetes mellitus, and contribute to the development of diabetes mellitus in patients using corticosteroids for a long time.
Mental disorders
With the use of corticosteroids, various mental disorders are possible: from euphoria, insomnia, mood changes, personality changes to severe depression with the expression of psychotic manifestations.
In addition, pre-existing emotional instability and a tendency to psychotic reactions may increase with the use of corticosteroids.
Particular attention should be paid to the systemic use of corticosteroids in both patients and their relatives of the first degree, with pre-existing severe affective mental disorders. These disorders include depressive or manic-depressive illness or pre-existing steroid psychosis. Symptoms usually appear within days or weeks of starting therapy.
Most reactions disappear after dose reduction or discontinuation of the drug, although special treatment may be necessary.
There have been reactions from the psyche with the withdrawal of corticosteroids; their frequency is unknown.
Patients and their caregivers should be advised to see a doctor if the patient develops any mental health problems, especially if there is a suspicion that the patient is in a depressed mood or has suicidal thoughts.
Patients and their caregivers should be vigilant about possible mental disorders that may occur with or immediately after a gradual dose reduction or withdrawal of systemic steroids.
Destroy the CTBA on the part of the nervous system
Corticosteroids should be used with caution in patients with seizures and myasthenia gravis (see Adverse Reactions for myopathy).
Although controlled clinical trials have shown the effectiveness of corticosteroids in accelerating the reduction of acute symptoms of exacerbations of multiple sclerosis, they have not demonstrated the effect of corticosteroids on the end result or the natural course of this disease.
According to the results of these studies, relatively high doses of corticosteroids should be used to demonstrate a significant effect (see section "Dosage and Administration").
There have been reports of epidural lipomatosis in patients taking corticosteroids, usually in high doses with prolonged use.
Visual disorders
In case of eye damage caused by glaucoma (or in the case of the presence of this disease in close relatives) or herpes simplex virus, corticosteroids should be used with caution, since this may lead to corneal perforation.
With prolonged use of corticosteroids, posterior subcapsular cataract and nuclear cataract (especially in children), exophthalmos or increased intraocular pressure may develop, which can lead to glaucoma with possible damage to the optic nerve.
Patients taking glucocorticoids are more likely to develop secondary eye infections caused by fungi and viruses.
Corticosteroid therapy has been associated with a developmental disorder that can lead to retinal detachment.
Heart disorders
The negative effects of glucocorticoids on the cardiovascular system, such as dyslipidemia and arterial hypertension, with their long-term use in high doses, may contribute to the appearance of additional cardiovascular side effects in patients with pre-existing cardiovascular risk factors.
In this regard, corticosteroids should be rationally used in such patients, as well as take into account the modification of risk factors and, if necessary, additionally monitor cardiac activity. Low doses and alternative therapy can reduce the incidence of complications with corticosteroid therapy. In patients with congestive heart failure, systemic corticosteroids should be used with caution and only if absolutely necessary.
Particular care is required when using systemic corticosteroids in patients with recent myocardial infarction (reported myocardial rupture), frequent monitoring of the patient's condition is required. Caution should be exercised in patients receiving cardioactive drugs such as digoxin due to steroid- induced electrolyte imbalance / potassium loss.
Vascular disorders
Cases of thrombosis, including thromboembolism, have been reported with the use of corticosteroids.
Caution should be exercised when prescribing corticosteroids to patients who have thromboembolic disorders or may be susceptible to them.
Corticosteroids should be used with caution in patients with hypertension.
Disorders from the gastrointestinal tract
High doses of corticosteroids can cause acute pancreatitis.
There is no consensus that corticosteroids alone cause gastric ulcer disease during therapy.
Corticosteroids can make it difficult to diagnose gastrointestinal complications because they reduce pain and can mask the symptoms of peptic ulcer disease. In combination with NSAIDs, the risk of developing gastrointestinal ulcers increases. Therefore, aspirin and nonsteroidal anti-inflammatory drugs should be used with caution in combination with corticosteroids.
Corticosteroids should be used with caution in ulcerative colitis if there is a risk of gastrointestinal wall perforation, abscess formation, or other purulent infection; with diverticula; in the case of recently imposed intestinal anastomoses; with active or latent peptic ulcer.
Dist roystva hepatobiliary system
Particular attention should be paid to the use of systemic corticosteroids in patients with liver cirrhosis and hepatic insufficiency.
Reported isolated hepatobiliary disorders, most of which were reversible after drug withdrawal.
H eobhodim careful monitoring.
Disorders of the s musculoskeletal system
Cases of acute myopathy have been reported with the use of high-dose corticosteroids, most often in patients with disorders of neuromuscular transmission (eg, myasthenia gravis) or in patients receiving therapy with anticholinergics that block neuromuscular transmission (eg, pancuronium). This acute myopathy is generalized, can affect the muscles of the eyes and respiratory muscles and lead to tetraparesis.
There may be an increase in creatine kinase levels.
It may take several weeks to several years to improve the clinical condition or recovery after corticosteroid withdrawal.
Osteoporosis is one of the side reactions that is often observed, but rarely diagnosed, develops with prolonged use and high doses of glucocorticoids.
With long-term therapy with methylprednisolone, it is necessary to consider the appointment of bisphosphonates to patients with osteoporosis or with risk factors for its development. Risk factors for osteoporosis are age 65 years, frequent fractures in history or family history, early menopause (up to 45 years), premenopausal and menorrhea, and low body weight.
The risk of developing osteoporosis can be minimized by adjusting the dose of methylprednisolone to the lowest therapeutic level.
Disorders of the check and urinary system
Corticosteroids should be used with caution in patients with renal impairment.
Laboratory and instrumental research
When using hydrocortisone or cortisone in medium and high doses, an increase in blood pressure, retention of salts and water, and an increase in potassium excretion are possible. These effects are observed less frequently with the use of synthetic derivatives of these drugs, except when they are used in high doses.
During long-term treatment with methylprednisolone in order to prevent hypokalemia, it is necessary to prescribe an appropriate diet with limited salt intake and take potassium supplements. All corticosteroids increase potassium excretion.
Injuries, etching and complications of procedures
Systemic corticosteroids are not indicated and, therefore, should not be used to treat traumatic brain injury. In a multicenter study, an increase in mortality was found at 2 weeks and 6 months after head injury in patients treated with methylprednisolone sodium succinate compared with patients receiving placebo. The causal relationship of this fact with the use of methylprednisolone sodium succinate has not been established.
Others
Since complications in treatment with glucocorticoids depend on the dose of the drug and the duration of therapy, in each case, the benefit / risk ratio should be assessed in determining the dose, duration of treatment and the mode of administration (daily or at intervals).
When treating with corticosteroids, the lowest dose should be prescribed that provides a sufficient therapeutic effect, and if it becomes possible to carry out a gradual dose reduction.
Aspirin and non-steroidal anti-inflammatory drugs should be used with caution in combination with corticosteroids.
After the use of systemic corticosteroids, the development of a pheochromocytoma crisis, which can be fatal, has been reported.
Corticosteroids should be administered to patients with suspected or established pheochromocytoma only after appropriate risk / benefit assessment.
When treating with glucocorticoids for a long time, it is recommended to regularly monitor blood pressure, determine the level of glucose in urine and blood, perform fecal occult blood tests, determine ESR parameters, and X-ray control of the spine.
Electrolyte balance should be carefully monitored in the combined use m etilprednizolona with diuretics.
Concomitant use with inhibitors of the isoenzyme CYP3A, including drugs containing cobicistat, is expected to increase the risk of developing systemic adverse reactions. The simultaneous use of such drugs should be avoided unless the benefit outweighs the risk of developing systemic adverse reactions of corticosteroids. In this case, careful monitoring of the patient's condition should be carried out for the manifestation of systemic side effects.
Use in the elderly
Elderly patients should be prescribed glucocorticoids with caution because of the increased risk of side effects (peptic ulcer, osteoporosis, and skin ulcers).
Application in children
In children receiving glucocorticoids for a long time every day, several times a day, growth retardation may be observed, so this dosing regimen should be used only for absolute indications.
Alternating therapy usually avoids or minimizes this side effect.
No carcinogenic and mutagenic effects of the drug, as well as its adverse effects on reproductive functions, were found.
Systemic corticosteroids should not be used in high doses in the treatment of patients with traumatic brain injury.
The drug contains lactose, therefore, meth- ilprednisolone is not recommended for patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Interaction with other medicinal products
Methylprednisolone is a substrate for the cytochrome P450 (CUR) enzyme, metabolized with the participation of the CYP3A4 enzyme, which is the dominant enzyme of the most abundant subtype of CYP in the liver of adults.
It catalyzes the 6-β- hydroxylation of steroids and is a key step in phase I metabolism for both endogenous and synthetic corticosteroids.
Many other compounds are also substrates of CYP3A4, some of them (like other drugs) alter the metabolism of glucocorticoids, inducing (enhancing activity) or inhibiting the isoenzyme CYP3A4.
CYP3A4 inhibitors - Drugs that inhibit the activity of CYP3A4 tend to decrease hepatic clearance and increase plasma concentrations of CYP3A4 substrate drugs such as methylprednisolone. In the presence of a CYP3A4 inhibitor, it may be necessary to titrate the dose of methylprednisolone to avoid steroid toxicity. CYP3A4 inhibitors include: grapefruit juice, macrolide antibiotics (troleandomycin).
CYP3A4 inducers - drugs that stimulate CYP3A4 activity, as a rule, increase hepatic clearance and reduce plasma concentrations of CYP3A4 substrate drugs. With the simultaneous use of these drugs, an increase in the dose of methylprednisolone may be required to achieve the desired result.
These drugs include antibacterial and anti-tuberculosis drugs - rifampicin ; anticonvulsants - phenytoin, phenobarbital.
CYP3A4 substrates - The presence of another CYP3A4 substrate may lead to inhibition or induction of hepatic clearance of methylprednisolone, with appropriate dose adjustments required. It is possible that side reactions associated with the isolated use of such drugs will be more likely when they are used simultaneously.

Special instructions
The use of corticosteroids during pregnancy is possible if the expected effect of treatment outweighs the potential risk to the fetus (there have been no strictly controlled and adequate safety studies). It is necessary to warn women of childbearing age about the possible risk to the fetus (corticosteroids cross the placenta). Careful monitoring of newborns whose mothers took corticosteroids during pregnancy is necessary (there is a risk of adrenal insufficiency in the newborn and fetus). Do not use in large doses, often, over a long period. Breastfeeding women should stop either breastfeeding or using the drug, especially in high doses (corticosteroids are excreted in breast milk and can inhibit the formation of endogenous corticosteroids, cause unwanted effects and inhibit growth in the baby).

Pregnancy and elbowing
Pregnancy
Animal studies have shown that high doses of corticosteroids in females can lead to fetal malformations.
In one retrospective study, mothers taking corticosteroids had an increased incidence of low birth weight infants.
Appropriate studies of the effect of corticosteroids on the human body have not been conducted. Since there is no clear evidence of the safety of corticosteroids during pregnancy, these drugs should only be prescribed if absolutely necessary. Some corticosteroids cross the placental barrier easily.
When deciding on the appointment of methylprednisolone to pregnant and lactating women, or women who may become pregnant, it is necessary to carefully assess the ratio of the benefits of using the drug and the potential risk for the mother, fetus and child.
Infants whose mothers received sufficiently high doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency, although adrenal insufficiency in neonates exposed to corticosteroids in utero is rare.
The effect of corticosteroids on the course and consequences of labor is unknown.
In newborns, whose mothers received long-term treatment with corticosteroids during pregnancy, the appearance of cataracts was recorded.
Breastfeeding period
Corticosteroids pass into breast milk. Corticosteroids, which are excreted in breast milk, can inhibit growth and interfere with endogenous glucocorticoid production in breastfed infants.
Since proper studies on the effect of glucocorticoids on reproductive function in humans have not been carried out, if it is necessary to use the drug for breastfeeding women, these drugs should be prescribed to nursing mothers only after a careful assessment of the benefit / risk ratio for the mother and the infant.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.