Depo-Medrol® (Depo-Medrol®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMethylprednisoloneMethylprednisolone
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    • Dosage form: & nbspfromInjection for injection
    Composition:

    Per 1 ml:

    of the active substance: methylprednisolone acetate - 40 mg;

    Excipients: macrogol 3350 29 mg, sodium chloride 8.7 mg, myristyl-γ-picolinium chloride 0.2 mg, sodium hydroxide (to adjust the pH to 3.5-7), hydrochloric acid (to adjust the pH to 3.5-7), water for injection up to 1 ml.

    Description:Finspension white.
    Pharmacotherapeutic group:Glucocorticosteroid
    ATX: & nbsp

    H.02.A.B.04   Methylprednisolone

    Pharmacodynamics:

    The drug is an injection form of synthetic methylprednisolone.Methylprednisolone acetate has a pronounced and prolonged anti-inflammatory, antiallergic and immunosuppressive activity and is used intramuscularly to achieve a prolonged systemic effect, and in situ as a means for local therapy. The prolonged action of the drug is due to the slow release of the active substance.

    Pharmacodynamics

    Methylprednisolone acetate has the same properties as methylprednisolone, but is less soluble and less metabolized, which explains the longer duration of its action. Methylprednisolone, penetrating through cell membranes, forms complexes with specific cytoplasmic receptors. Then these complexes penetrate into the cell nucleus, bind to DNA (chromatin) and stimulate the transcription of mRNA and the subsequent synthesis of various proteins (including enzymes), which explains the effect of methylprednisolone in systemic application. Methylprednisolone not only has a significant effect on the inflammatory process and immune response, but also affects carbohydrate, protein and fat metabolism.It also has an effect on the cardiovascular system, skeletal muscles and the central nervous system.

    Influence on the inflammatory process and immune response

    Most of the indications for the use of methylprednisolone is due to its anti-inflammatory, immunosuppressive and anti-allergic properties. Due to these properties, the following therapeutic effects are achieved:

    - decrease in the number of immunoactive cells in the inflammatory focus;

    - decreased vasodilation;

    - stabilization of lysosomal membranes;

    - inhibition of phagocytosis;

    - reduction in the production of prostaglandins and related compounds.

    The dose of 4.4 mg methylprednisolone acetate (4 mg methylprednisolone) has the same anti-inflammatory effect as 20 mg hydrocortisone. Methylprednisolone has only a minor mineralocorticoid activity (200 mg of methylprednisolone is equivalent to 1 mg of deoxycorticosterone).

    Influence on carbohydrate and protein metabolism

    Methylprednisolone has catabolic action against proteins. Released amino acids are converted in the process of gluconeogenesis in the liver into glucose and glycogen.Consumption of glucose in peripheral tissues is reduced, which can lead to hyperglycemia and glucosuria, especially in patients at risk of developing diabetes.

    Effect on fat metabolism

    Methylprednisolone has a lipolytic effect, which is primarily manifested in the limb region. Methylprednisolone also increases lipogenesis, which is most pronounced in the region of the chest, neck and head. All this leads to redistribution of fatty deposits. The highest pharmacological activity of methylprednisolone is manifested not after reaching the maximum concentration in the blood plasma, but after its decrease, therefore, its effect is primarily due to the effect on the activity of the enzymes.

    Pharmacokinetics:

    Methylprednisolone acetate is hydrolyzed by the action of cholinesterases of blood plasma with the formation of an active metabolite. In the human body methylprednisolone forms a weak, dislocating connection with albumin and transcortin. About 40-90% of methylprednisolone is in the bound state. Due to the intracellular activity of methylprednisolone, there is a pronounced difference between the half-life of plasma and the pharmacological half-life.

    Pharmacological activity persists even when the concentration of methylprednisolone in the blood is no longer determined. The duration of the anti-inflammatory activity of methylprednisolone is approximately equal to the duration of suppression of the hypothalamic-pituitary-adrenal (HHG) system.

    After i / m administration of the drug at a dose of 40 mg / ml, the maximum concentration (CmOh) in blood plasma was achieved on the average after 7.3 ± 1 hour (TmOh) and averaged 1.48 ± 0.86 μg / 100 ml (half-life = 69.3 hours). After a single intravenous injection of 40-80 mg of methylprednisolone acetate, the duration of suppression of the HGH system was 4 to 8 days.

    After intra-articular administration of 40 mg to each knee joint (total dose = 80 mg), the maximum plasma concentration was reached after 4-8 hours and was approximately 21.5 μg / 100 ml. The intake of methylprednisolone in the systemic bloodstream from the joint cavity was preserved for approximately 7 days, which is confirmed by the duration suppression of HGH system and results of determination of methylprednisolone concentrations in blood plasma.

    Metabolism of methylprednisolone is carried out in the liver, and this process is qualitatively similar to that of cortisol. The main metabolites are inactive 20β-hydroxymethylprednisolone and 20β-hydroxy-6αmethylprednisone. Metabolism is carried out mainly through the isoenzyme CYP3A4. Metabolites are excreted by the kidneys in the form of glucuronides, sulfates and unconjugated compounds. These conjugation reactions occur mainly in the liver and partially in the kidneys.

    The average half-life for all forms of methylprednisolone is from 1.8 to 5.2 hours. The estimated volume of distribution is approximately 1.4 l / kg, and its total clearance is approximately 5 to 6 ml / min / kg.

    Like many other isoenzyme substrates CYP3A4, methylprednisolone can also be a substrate of ATP-linked transport proteins of P-glycoprotein, affecting the distribution in tissues and interaction with other drugs.
    Indications:

    GCS should be used only as a symptomatic treatment, with the exception of some endocrine disorders, in which they are used as substitution therapy.

    A. INTENDED USE

    Methylprednisolone acetate (Depo-MEDROL®) is not used to treat acute life-threatening conditions. If a rapid hormonal effect of maximum intensity is required, intravenously a highly soluble methylprednisolone sodium succinate (SOLO-MEDROL®) is administered intravenously.

    If oral administration is not possible, if the dose, dosage form and route of administration of the drug are adequate for the treatment of the condition / disease, then intramuscular use of the drug is indicated for the following diseases:

    1. Endocrine diseases

    - Primary and secondary adrenal insufficiency (drugs of choice - hydrocortisone or cortisone; if necessary in combination with mineralocorticoids, especially in pediatric practice).

    - Acute adrenal insufficiency (drugs of choice - hydrocortisone or cortisone; it may be necessary to add mineralocorticoids).

    - Congenital hyperplasia of the adrenal glands.

    - Hypercalcemia on the background of cancer.

    - Subacute thyroiditis.

    2. Rheumatic diseases

    As an additional tool for maintenance therapy (nonsteroidal anti-inflammatory drugs, kinesiotherapy, physiotherapy, etc.) and for short-term use (for removing the patient from an acute condition or exacerbating the process) with the following diseases:

    - Psoriatic arthritis.

    - Ankylosing spondylitis.

    For the following diseases, the drug should be used as far as possible in situ:

    - Posttraumatic osteoarthritis.

    - Synovitis in osteoarthritis.

    - Rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases, maintenance therapy with low doses may be required).

    - Acute and subacute bursitis.

    - Epicondylitis.

    - Acute nonspecific tenosynovitis.

    - Acute gouty arthritis.

    3. Collagenoses

    During an exacerbation or in some cases as a maintenance therapy for the following diseases:

    - Systemic lupus erythematosus.

    - Systemic dermatomyositis (polymyositis).

    - Acute rheumatic myocarditis.

    4. Skin diseases

    - Pemphigus.

    - Malignant exudative erythema (Stevens-Johnson syndrome).

    - Exfoliative dermatitis.

    - Mushroomed mycosis.

    - Bullous herpetiform dermatitis (the drug of choice - sulfone, systemic application of GCS is adjuvant).

    5. Allergic conditions

    For relief of severe and disabling allergic conditions / diseases that do not respond to adequate traditional therapy:

    - Bronchial asthma.

    - Contact dermatitis.

    - Atopic dermatitis.

    - Serum sickness.

    - Seasonal or all-the-year-round allergic rhinitis.

    - Medicinal allergy.

    - Reactions to transfusion / administration of drugs by type of urticaria.

    6. Ophthalmic diseases

    Severe acute and chronic allergic (allergic conjunctivitis, allergic ulcers of the angle of the eye) and inflammatory processes with eye damage, such as:

    - Uveitis and inflammatory diseases of the eyes (iritis, iridocyclitis, inflammation of the anterior chamber of the eye, chorioretinitis, optic neuritis, keratitis), not responding to the use of local corticosteroids.

    7. Diseases of the gastrointestinal tract (GIT)

    To excrete a patient from a critical condition with the following diseases:

    - Ulcerative colitis (systemic therapy).

    - Crohn's disease (systemic therapy).

    8. Diseases of the respiratory system

    Symptomatic sarcoidosis.

    - Berylliosis.

    - Focal or disseminated pulmonary tuberculosis (used in combination with appropriate antituberculous chemotherapy).

    - Leffler's syndrome, which is not amenable to therapy by other methods.

    - Aspiration pneumonitis.

    9. Hematological diseases

    - Acquired (autoimmune) hemolytic anemia.

    - Secondary thrombocytopenia in adults.

    - Erythroblastopenia (large thalassemia).

    - Congenital (erythroid) hypoplastic anemia.

    10. Oncological diseases

    As a palliative therapy for the following diseases:

    - Leukemia and lymphomas in adults.

    11. Edema Syndrome

    For induction of diuresis or treatment of proteinuria in nephrotic syndrome, idiopathic type or due to systemic lupus erythematosus.

    12. Nervous system

    - Multiple sclerosis in the phase of exacerbation.

    13. Other indications for use

    - Tuberculous meningitis with a subarachnoid block or with a block threat, in combination with appropriate anti-tuberculosis chemotherapy.

    - Trichinosis with damage to the nervous system or myocardium.

    B. INTRASUAL, PERIARTICULAR, INTURBURSAL APPLICATION AND INTRODUCTION IN SOFT FABRICS (see section "Special instructions").

    As an auxiliary therapy for short-term use (for removing a patient from an acute condition or exacerbating a process) with the following diseases:

    - Synovitis in osteoarthritis.

    - Rheumatoid arthritis.

    - Acute and subacute bursitis.

    - Acute gouty arthritis.

    - Epicondylitis.

    - Acute nonspecific tenosynovitis.

    B. INTRODUCTION TO THE PATHOLOGICAL CENTER

    Keloid scars and localized foci of inflammation with:

    - Red flat-leafed vertebrae (Wilson).

    - Psoriatic plaques.

    - Ring-shaped granulomas.

    - Simple chronic ear infection (neurodermatitis).

    - Discoid lupus erythematosus.

    - Diabetic lipodystrophy.

    - Nesting alopecia.

    The drug DEPO-MEDROL® can also be shown with tendon and aponeurotic ganglia (cysts of the tendon sheath).

    Contraindications:

    - Intrathecal administration.

    - Intravenous administration.

    - Epidural introduction.

    - Systemic fungal infections.

    - An established hypersensitivity to methylprednisolone or any other component of the drug.

    - Simultaneous use of live or diluted vaccines with immunosuppressive doses of DEPO-MEDROL®.

    - Breastfeeding period.

    - Idiopathic thrombocytopenic purpura.

    - Edema of the brain due to craniocerebral trauma (administration of high doses of the drug).

    Carefully:

    Eye damage caused by the herpes simplex virus, as this can lead to corneal perforation, open-angle glaucoma; ulcerative colitis,if there is a threat of perforation, development of an abscess or other purulent infection, and diverticulitis; presence of fresh intestinal anastomoses; active or latent peptic ulcer, esophagitis, gastritis, peptic ulcer and duodenal ulcer; kidney failure; diabetes mellitus, hyperlipidemia; convulsive syndrome; arterial hypertension; osteoporosis; myasthenia gravis gravis, when GCS is used as a primary or complementary therapy; mental disorders in the anamnesis; in children; varicella, measles; latent or active tuberculosis; thyroid dysfunction; chronic heart failure, acute and subacute myocardial infarction; AIDS; severe bacterial or viral infectious diseases, strongyloidiasis (increases the risk of superinfection, masks the symptoms of the disease); when combined with acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs), anticholinergic drugs.

    You should avoid taking the drug in patients with Isenko-Cushing's disease.

    The drug should be used with caution in elderly patients due to increased risk of osteoporosis and hypertension (due to fluid retention).

    Pregnancy and lactation:

    A number of studies in animals have shown that the introduction of SCS to females can lead to a teratogenic effect. Nevertheless, there are no prerequisites to the fact that SCS can cause congenital anomalies in children whose mothers received SCS during pregnancy. Since adequate studies of the effect of methyl prednisolone acetate on reproduction in humans have not been carried out, the drug Depo-MEDROL® should be prescribed during pregnancy only in the event that the expected therapeutic effect for the mother exceeds the risk of adverse effects of the drug on the fetus. In case of withdrawal of the drug during pregnancy after prolonged therapy, it is necessary to gradually reduce the dose.

    SCS easily penetrate the placenta. There was an increase in the number of children with low birth weight in mothers who received methylprednisolone. In studies, it was found that the risk of giving birth to children with low body weight is dose-dependent and, thus, can be minimized by the administration of lower doses of GCS.

    Children born to mothers who received sufficiently high doses of DEPO-MEDROL® during pregnancy should be closely monitored,so that the signs of adrenal insufficiency can be detected in a timely manner. Adrenal insufficiency is rare in newborns whose mothers were taking SCS during pregnancy. Cases of cataract development in newborns, whose mothers were taken methylprednisolone during pregnancy.

    The effect of GCS on the course and outcome of delivery is unknown.

    Methylprednisolone penetrates into breast milk in amounts that can cause growth retardation and interaction with endogenous GCS, so if you need to use the drug Depo-MEDROL® During breastfeeding, breastfeeding should be discontinued.

    Dosing and Administration:

    - Intramuscular;

    - intraarticular, periarticular, intra-bursal introduction or introduction into soft tissues;

    - introduction to the pathological focus.

    INTRODUCTION TO THE PATHOLOGICAL FOCUS FOR ACHIEVING A LOCAL EFFECT

    Despite the fact that treatment with DEPO-MEDROL® reduces the symptoms of the disease, it has no effect on the cause of the inflammatory process, so it is necessary to carry out the usual therapy for each specific disease.

    Rheumatoid arthritis and osteoarthritis

    Dose for intraarticular administration depends on the size of the joint, as well as on the severity of the condition of the patient. In the case of chronic diseases, the interval between injections may be one to five or more weeks, depending on the degree of improvement achieved after the first injection. The following doses are given as general recommendations (see table):

    Joint size

    Name of joint

    Dose range

    Large

    Knee

    Ankle

    Brachial

    20-80 mg

    Average

    Elbow joint

    Wrist Band

    10-40 mg

    Small

    Metacarpophalangeal

    Interphalangeal

    Breast-clavicular

    Acromioclavicular

    4-10 mg

    Procedure. Before carrying out intraarticular injection, it is recommended to evaluate the anatomy of the affected joint.

    For a full-fledged anti-inflammatory action, it is important that the injection be carried out into the synovial cavity. It is necessary to follow the rules of aseptic and antiseptic as well as with lumbar puncture. Sterile needle 20-24 G (put on a dry syringe) is quickly inserted into the synovial cavity.

    The method of choice is infiltration anaesthesia procaine.

    To control the entry of the needle into the joint cavity, several drops of intraarticular fluid are aspirated. When choosing the site of the injection, which is individual for each joint, the proximity of the synovial cavity to the surface (as close as possible) is taken into account, as well as the path of passage of large vessels and nerves (as far as possible). The needle remains in place, the syringe with aspirated fluid is removed and replaced with another syringe containing the required amount of DEPO-MEDROL®. Then slowly pull the plunger toward yourself and aspirate the synovial fluid to make sure that the needle is still in the synovial cavity. After the injection, several light movements in the joint should be made, which helps to mix the suspension with the synovial fluid. Place the injection close a small sterile bandage.

    The drug can be injected into the knee, ankle, elbow, shoulder, metacarpophalangeal, interphalangeal and hip joints. Sometimes there are difficulties with the introduction of the hip joint, so you should avoid getting into large blood vessels.In the following joints, injections are not made: anatomically unattainable joints, for example, intervertebral articulations, including the sacroiliac joint, in which there is no synovial cavity. Inefficiency of therapy is most often the result of an unsuccessful attempt to penetrate the joint cavity. When the drug is injected into the surrounding tissues, the effect is insignificant or absent altogether. If the therapy did not give positive results in the case when getting into the synovial cavity did not cause doubt, which was confirmed by aspiration intra-articular fluid, repeated injections are usually useless.

    Local therapy does not affect the process underlying the disease, therefore, complex therapy, including basic anti-inflammatory therapy, physiotherapy and orthopedic correction.

    After intraarticular administration of the drug DEPO-MEDROL® care should be taken not to overload the joints in which a symptomatic improvement is noted in order to avoid a stronger joint damage compared to what was before the start of therapy with DEPO-MEDROL®.

    DEPO-MEDROL® can not be injected into unstable joints. In some cases, repeated intraarticular injections can lead to instability of the joint. In some cases it is recommended to perform X-ray inspection to detect damage.

    If a local anesthetic is used prior to the administration of DEPO-MEDROL®, you should carefully read the instructions for use of this anesthetic to ensure that all necessary precautions are taken.

    Bursitis. After treatment of the area around the site of injection with an antiseptic, local infiltration anesthesia is performed with a 1% solution of procaine. on a dry syringe put on a needle 20-24 G. which is introduced into the articular bag, and then aspirate the liquid. The needle is left in place, and the syringe with aspirated liquid is removed and a syringe containing the necessary dose of the drug is placed in its place. After the injection, the needle is removed and a sterile bandage is applied.

    Vaginal tendon cyst, tendonitis, epicondylitis. In the treatment of conditions such as tendonitis or tendosynovitis, care should be taken to ensure that the suspension is inserted into the tendon sheath and not into the tendon tissue.The tendon can easily be palpated if you hold your hand along it. In the treatment of conditions such as epicondylitis, the most painful area should be identified and the suspension should be introduced into it by the creeping infiltrate method. In the cysts of the tendons of the vagina, the suspension is injected directly into the cyst. In many cases it will be possible to achieve a significant reduction in the size of the cystic tumor and even its disappearance after a single injection of the drug.

    Each injection should be done in accordance with the rules of asepsis and antiseptics (skin treatment antiseptic).

    The dose is selected depending on the nature of the process and is 4-30 mg. If the recurrence or chronic course of the process may require repeated injections.

    Skin diseases. After treating the skin with an antiseptic, for example, 70% alcohol, 20-60 mg of the suspension is injected into the lesion. With a large surface of the lesion, the DotA 20-40 mg is divided into several parts and injected into various parts of the affected surface. With the introduction of the drug should be careful, since it is necessary to avoid whitening of the skin, which can in the future lead to peeling.Usually, 1-4 injections are given, the interval between injections depends on the type of pathological process and the length of the period of clinical improvement achieved after the first injection.

    INTRAIMIC INTRODUCTION TO ACHIEVE THE SYSTEM EFFECT

    The dose of the drug for the / m administration depends on the disease to be treated.

    To obtain a lasting effect, calculate the weekly dose, multiplying the daily dose for oral administration by 7, and injecting it as one intravenous injection.

    The dose should be selected individually, taking into account the severity of the disease and the patient's response to therapy. Children (including infants) are treated with a lower dose, which is chosen primarily taking into account the severity of the disease, rather than using permanent schemes based on age or body weight. The course of treatment should be on the possibilities are shorter. Treatment is carried out under constant medical supervision.

    Hormone therapy is an adjunct to conventional therapy, but does not replace it. The dose of the drug should be reduced gradually, the withdrawal of the drug is also carried out gradually, if it was introduced for longer than a few days.The main factors determining the choice of dose are the severity of the disease, the prognosis, Pexpected duration disease, as well as the patient's response to therapy. If chronic a period of spontaneous remission arose, treatment should be discontinued. With prolonged therapy, routine laboratory tests, such as general urinalysis, determination blood glucose concentrations 2 hours after ingestion, measurement blood pressure, body weight, chest x-ray should be carried out regularly at regular intervals.

    Patients with peptic ulcer and duodenal ulcer in history or with pronounced dyspepsia are advised to conduct an X-ray examination of the upper gastrointestinal tract. With prolonged therapy, endoscopic examination is also recommended in such patients.

    Patients from adrenogenital syndrome it is enough to inject in / m 40 mg once every 2 weeks. For maintenance therapy for patients with rheumatoid arthritis, the drug is administered once a week in / m of 40-120 mg.

    Dose for treatment with DEPO-MEDROL® in patients with skin diseases, allowing to achieve a good clinical effect, is 40-120 mg IM once a week for 1-4 weeks. In acute severe dermatitis caused by poison contained in ivy, it is possible to eliminate the manifestations within 8-12 hours after a single IM injection of 80-120 mg. With chronic contact dermatitis, repeated injections may be effective at intervals of 5-10 days. With seborrheic dermatitis, it is enough to administer 80 mg once a week to control the condition.

    After the / m introduction 80-120 mg patients with bronchial asthma the disappearance of symptoms occurs within 6-48 hours, and the effect persists for several days or even 2 weeks.

    In patients with allergic rhinitis (hay fever) IM injection of 80-120 mg can also lead to the elimination of symptoms of acute rhinitis within 6 hours, with the effect lasting from several days to 3 weeks.

    If the symptoms of stress develop in the disease to which the therapy is directed, the dose of the suspension should be increased. To obtain a quick maximum effect, intravenous administration methylprednisolone sodium succinate, characterized by rapid solubility.

    Side effects:

    When injecting the drug intrathecally or epidurally (see the section "Contraindications"), the following adverse reactions were noted: arachnoiditis, dysfunction of the gastrointestinal tract or bladder, headache, meningitis, paresthesia / paraplegia, convulsions, sensitivity disorders. The frequency of these unwanted reactions is unknown.

    - Violations from the blood and lymphatic system: leukocytosis.

    - Violations from the exchange substances and nutrition: metabolic acidosis, lipomatosis, sodium retention, fluid retention, hypokalemic alkalosis, dyslipidemia, impaired glucose tolerance, increased insulin requirements or in oral hypoglycemic drugs in patients with diabetes mellitus, increased appetite (which may lead to weight gain), secondary adrenal failure.

    When synthetic derivatives such as methylprednisolone acetate are used, mineralocorticoid effects are less common than with cortisone or hydrocortisone.

    - Heart Disease: chronic heart failure in patients with a corresponding predisposition, bradycardia, tachycardia,heart rhythm disturbances, hypertrophic cardiomyopathy in premature infants, myocardial rupture in patients with acute or subacute myocardial infarction, cardiac arrest, cardiac enlargement.

    - Vascular disorders: increased blood pressure, lower blood pressure, thromboembolism (including thromboembolism of the pulmonary artery), thrombophlebitis, vasculitis, thrombosis, vascular collapse.

    - Disturbances from musculoskeletal and connective tissue: myopathy, muscle weakness, osteoporosis, pathological fractures, osteonecrosis, decreased muscle mass, neuropathic arthropathy. arthralgia, myalgia, arthropathy by the type of Charcot.

    - Violations of the genitals and breast: irregular menstrual cycle.

    - Disorders from the gastrointestinal tract: peptic ulcer (possible perforation and bleeding), gastric bleeding, pancreatitis, ulcerative esophagitis, esophagitis, intestinal wall perforation, abdominal pain, bloating, diarrhea, dyspepsia, nausea, peritonitis *.

    - Disturbances from the liver and bile ducts: enlargement of the liver,there may be a temporary and moderate increase in the activity of transaminases and alkaline phosphatase in the blood plasma, but this is not associated with any clinical syndrome and is reversible when the drug is withdrawn.

    - Disturbances from the skin and subcutaneous tissues: petechiae and ecchymosis, thinning and fragility of the skin, angioedema, striae, hirsutism, rash, erythema, urticaria, skin itch, acne, hyperhidrosis, hyperpigmentation or hypopigmentation, skin and subcutaneous tissue atrophy, allergic dermatitis.

    - Onrupture from the nervous system: increased intracranial pressure (with edema of the optic nerve disk (benign intracranial hypertension)), cognitive disorders, convulsions, amnesia, dizziness, headache, epidural lipomatosis, neuritis, neuropathy, paresthesia.

    - Disorders from the endocrine system: the development of the Itenko-Cushing syndrome, hypopituitarism, the syndrome of "cancellation" of the SCS, the growth retardation in children.

    - Disorders from the side of the organ of vision: cataract, increased intraocular pressure, glaucoma, exophthalmos, cases of blindness associated with local administration of the drug to pathological foci located in the face and head area, chorioretinopathy.

    - Immune system disorders: infectious diseases, infections caused by opportunistic pathogens, hypersensitivity reactions, including anaphylaxis.

    - Disorders of the psyche: affective disorders (including affective lability, depressive mood, euphoria, drug dependence, suicidal thinking), psychotic disorders (including mania, delusions, hallucinations, schizophrenia), confusion, disturbed thinking, anxiety, personality changes, changes in mood moods, inadequate behavior, insomnia, irritability.

    - Hearing disorders and labyrinthine disturbances: Vertigo.

    - Disturbances from the respiratory system, chest and mediastinal organs: hiccough, pulmonary edema.

    - General disorders and disorders in place of administration: peripheral edema, reactions at the injection site, infection at the injection site, weakness, fatigue, anaphylactoid reactions, anaphylactic or allergic reactions, post-injection exacerbation after administration to the synovial fluid, sterile abscess, hypertrichosis, deterioration of wound healing.

    - Violations identified at clinical and laboratory studies: decreased carbohydrate tolerance, decreased potassium concentration in blood plasma, increased urinary calcium concentration, increased uric acid concentration in the blood, slowed down reactions to skin tests, increased or decreased motility and quantity of spermatozoa.

    - Injuries, intoxications and complications manipulations: compression fracture of the vertebrae, tendon rupture.

    * The main and severe complication in diseases of the digestive tract (perforation of the walls of the stomach and intestines, pancreatitis) is peritonitis (see section "Special instructions").

    Overdose:

    Clinical syndrome of acute overdose of methylprednisolone acetate does not exist. Reports of acute toxicity and / or lethal outcomes due to SCS overdose are rare.

    Repeated frequent use of the drug (daily or several times a week) for a long period can lead to the development of the Itenko-Cushing syndrome. It should stop using the drug; but it must be taken into account that its abrupt cancellation can lead to a "ricochet" adrenal insufficiency. Specific treatment is not required.Supportive and symptomatic therapy should be provided. There is no specific antidote. Methylprednisolone is displayed during dialysis.

    Interaction:

    Inhibitor inhibitors CYP3A4 - can suppress the metabolism of methylprednisolone, reduce its clearance and increase the concentration in the blood plasma. In this case, in order to avoid overdose phenomena, a dose of methylprednisolone should be titrated.

    Inductors of isoenzyme CYP3A4 - can increase the clearance of methylprednisolone. This is manifested by a decrease in the concentration of methylprednisolone in the blood plasma, which may require increasing the dose of the drug to obtain the desired effect.

    Substrates of the isoenzyme CYP3A4 - in the presence of another isoenzyme substrate CYP3A4 methylprednisolone clearance may vary, which may require appropriate dose adjustment of methylprednisolone. There is a chance that adverse reactions, manifested when using drugs in the form of monotherapy, can occur more often with the simultaneous use of drugs.

    The following examples of drug interactions may have important clinical implications.

    Class or type of medicinal product

    - drug or substance

    Interaction / effect

    Antibacterial drugs

    - isoniazid

    Inhibitor of isoenzyme CYP3A4. In addition, there is a possibility that methylprednisolone increases the degree of acetylation and clearance of isoniazid.

    Antibiotic, anti-tuberculosis

    -rifampicin

    Inductor of isoenzyme CYP3A4.

    Anticoagulants (for oral administration)

    Methylprednisolone has a variety of effects on the effect of indirect anticoagulants. Both enhancement and reduction of the effect of anticoagulants taken simultaneously with methylprednisolone are reported. To maintain the necessary effect of the anticoagulant, constant monitoring of the coagulogram is necessary.

    Anticonvulsants

    - carbamazepine

    Inductor and substrate of isoenzyme CYP3A4.

    Anticonvulsants

    - phenobarbital

    - phenytoin

    Inductors of isoenzyme CYP3A4.

    Anticholinergic drugs

    - neuromuscular blockers

    The drug DEPO-MEDROL® can influence anticholinergic drugs.

    1. reported cases of acute myopathy with the simultaneous use of high doses of the drug Depo-MEDROL® and anticholinergic drugs, such as blockers of neuromuscular transmission (see section "Side effect").

    2. antagonism of the effect of blockade of pancuronium and vecuronium was noted with simultaneous application with the drug Depo-MEDROL®. This effect can be expected with any neuromuscular blocking blocker.

    Anticholinesterases

    SCS can reduce the effect of anticholinesterases in patients with myasthenia gravis gravis.

    Hypoglycemic drugs

    Since DEPO-MEDROL® can increase the concentration of glucose in the blood plasma, it is necessary to adjust the dose of hypoglycemic drugs.

    Antiemetic drugs

    -aprepitant

    - fosaprepitant

    Inhibitors and substrates of isoenzyme CYP3A4.

    Antifungal drugs

    - itraconazole

    - ketoconazole

    Inhibitors and substrates of isoenzyme CYP3A4.

    Antiviral drugs

    - HIV protease inhibitors

    Inhibitors and substrates of isoenzyme CYP3A4.

    1) HIV protease inhibitors, such as indinavir and ritonavir, can increase the concentration of methylprednisolone in the blood plasma.

    2) GCS can induce the metabolism of HIV protease inhibitors, which leads to a decrease in their concentration.

    Aromatase inhibitors

    - aminoglutethimide

    Suppression of the adrenal function induced by aminoglutethimide can inhibit the endocrine changes caused by prolonged therapy with DEPO-MEDROL®.

    Calcium channel blockers

    - diltiazem

    Inhibitors and substrates of isoenzyme CYP3A4.

    Oral contraceptive drugs

    - ethinyl estradiol / norethindrone

    Inhibitors and substrates of isoenzyme CYP3A4.

    Grapefruit juice

    Inhibitor of isoenzyme CYP3A4.

    Immunosuppressive drugs

    - cyclosporine

    Inhibitors and substrates of isoenzyme CYP3A4.

    1. The simultaneous use of methylprednisolone and cyclosporine causes mutual inhibition of metabolism, which can lead to an increase in the concentration in the blood plasma of one or both drugs. Therefore, it is likely that the side effects associated with the use of each of these drugs as monotherapy, with their joint application may occur more often.

    2. When joint use of these drugs, cases of seizures were noted.

    Immunosuppressive drugs

    - cyclophosphamide

    - tacrolimus

    Substrates of the isoenzyme CYP3A4.

    Antibiotics-macrolides

    - clarithromycin

    - erythromycin

    Inhibitors and substrates of isoenzyme CYP3A4.

    Antibiotics-macrolides

    - troleandomycin

    Inhibitor of isoenzyme CYP3A4.

    NSAIDs high doses of aspirin (acetylsalicylic acid)

    1. probably an increase in the incidence of gastrointestinal bleeding and ulceration with the simultaneous use of the drug Depo-MEDROL® and NSAIDs.

    2. Methylprednisolone can increase the clearance of acetylsalicylic acid, taken at high doses for a long period, which can lead to a decrease in the concentration of salicylates in the blood plasma. With the abolition of methylprednisolone therapy, the concentration of salicylates in the blood plasma increases, which can lead to an increased risk of salicylate toxicity. Caution is advisable to use acetylsalicylic acid in combination with the drug Depo-MEDROL®.

    Drugs that reduce the concentration of potassium in the blood plasma

    With the simultaneous use of the drug Depo-MEDROL® and drugs that reduce the concentration of potassium in the blood plasma (eg, diuretics), patients should be carefully monitored for the development of hypokalemia. It should also be noted that there is an increased risk of hypokalemia with simultaneous use of DEPO-MEDROL® and xanthines or β2agonists.

    Cardiac glycosides

    In patients with hypokalemia with the simultaneous use of methylprednisolone and cardiac glycosides, the risk of arrhythmias is increased.

    Due to the possibility of pharmaceutical incompatibility, DEPO-MEDROL® should not be diluted ormixed with other solutions.

    Methylprednisolone can suppress the reaction to conducting skin tests.

    Special instructions:

    Use strictly according to the doctor's prescription to avoid complications.

    - Preparations for parenteral administration before use should be subjected to visual inspection to detect foreign particles and discoloration of the preparation.

    - Vials should not be stored upside down! Shake well before use.

    - One bottle can not be used to administer several doses; After introducing the required dose, the vial with the suspension remains to be destroyed.

    - DEPO-MEDROL® should not be administered by any means other than those listed in the "Application and dose" section. There are reports of severe complications associated with administering the drug intrathecally or epidurally. It is necessary to take measures, preventing the introduction of the drug intravascularly.

    - Since crystals of methylprednisolone suppress inflammatory reactions, their presence can cause degradation of cellular and extracellular elements of connective tissue, which in rare cases manifests itself as a deformation of the skin at the injection site.The degree of expression of these changes depends on the amount of methylprednisolone administered. After complete absorption of the drug (usually after a few months), complete regeneration of the skin at the injection site occurs.

    - To minimize the likelihood of developing skin or subcutaneous tissue atrophy, care should be taken not to exceed the recommended dose for parenteral administration. If possible, the affected area should be mentally divided into several areas and into each of them to inject part of the total dose of the drug. When performing intraarticular and intramuscular injections, care must be taken not to inject the drug into the skin, or to avoid getting the drug into the skin, and also to accidentally not inject the drug into the deltoid muscle, as this can lead to the development of subcutaneous tissue atrophy.

    - If patients receiving methylprednisolone therapy may or have been exposed to severe stress, higher doses of methylprednisolone should be administered before, during and after this exposure.

    - When using the drug Depo-MEDROL® at therapeutic doses for a long period may develop suppression of the HGH system (secondary adrenal failure). The degree and duration of adrenal insufficiency are individual in each patient and depend on the dose, frequency of administration, time of administration and duration of therapy.

    The severity of this effect can be reduced by using the drug every other day or by gradually reducing the dose. This type of relative insufficiency can continue for several months after the end of treatment, therefore, in any stressful situations during this period, the drug DEPO-MEDROL®.

    - In addition, the development of acute adrenal insufficiency, leading to a lethal outcome, is possible with a sharp cancellation of the drug DEPO-MEDROL®.

    - The "withdrawal" syndrome, apparently not related to adrenal insufficiency, can also arise due to the abrupt withdrawal of DEPO-MEDROL®.

    This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, skin flaking, myalgia, weight loss and / or lowering blood pressure.

    It is assumed that these effects arise due to a sharp fluctuation in the concentration of methylprednisolone in the blood plasma, and not because of a decrease in the concentration of methylprednisolone in the blood plasma.

    - In patients with hypothyroidism, there is an increase in the effect of the drug Depo-MEDROL®.

    - SCS can erase the clinical picture of an infectious disease, when they are used, new infections can develop, and susceptibility to infections may increase. Against the background of methylprednisolone therapy, resistance may decrease organism to infection, as well as the ability of the body to localize the infection process. The development of infections caused by various pathogenic organisms, such as viruses, bacteria, fungi, protozoa or helminths that are localized in various human body systems, can be associated with the use of methylprednisolone, both as monotherapy and in combination with other drugs by immunosuppressants, affecting the cellular immunity, humoral immunity or the function of neutrophils. These infections can be mild, however, in some cases, a severe course and even a lethal outcome is possible.Moreover, the higher doses of methylprednisolone are used, the higher the probability of developing infectious complications.

    In case of acute infection, the drug should not be administered intraarticularly, into the joint bag and into the vagina of the tendons of the muscles; I / m administration is only possible after selecting the appropriate antimicrobial / antiparasitic therapy. Patients receiving drugs that suppress the immune system are more susceptible to infections than healthy individuals. For example, chicken pox and measles may have a more severe course, up to a lethal outcome, in unimmunized children or in adults receiving DEPO-MEDROL®.

    - Use DEPO-MEDROL® in patients with confirmed or suspected parasitic infections (eg, strongyloidosis) with caution. In such patients, immunosuppression induced by methylprednisolone may lead to strongyloid hyperinfection and dissemination with a wide spread of larvae in the body, which is often accompanied by severe enterocolitis and potentially lethal Gram-negative septicemia.

    - It is recommended to exclude latent or active amoebiasis prior to the use of GCS in patients with diarrhea of ​​unclear etiology or returned from tropical countries.

    - With prolonged use of methylprednisolone, posterior subcapsular cataracts and nuclear cataracts (especially in children), exophthalmos or increased intraocular pressure may develop, which can lead to glaucoma with possible damage to the optic nerve; the likelihood of developing secondary infections caused by fungi and viruses increases.

    - Therapy with methylprednisolone may lead to the development of central serous chorioretinopathy, which in turn can lead to detachment of the retina.

    - The use of GCS in patients with eye disease of the viral etiology (herpes virus) is not recommended in view of the risk of corneal perforation.

    - In animal studies, it has been shown that the use of GCS leads to a decrease in fertility.

    - It is necessary to closely monitor the growth and development of children on long-term therapy with DEPO-MEDROL®. In children receiving methylprednisolone therapy for a long time every day, growth may slow down. This mode of administration should be used only in the most severe conditions. The risk of development of growth retardation in children on the background of long-term therapy can be reduced with the dosage regimen of the drug every other day.

    - Children receiving long-term therapy with DEPO-MEDROL® are at increased risk for developing intracranial hypertension.

    - The use of high doses of methylprednisolone may lead to the development of pancreatitis in children.

    - The efficacy of DEPO-MEDROL® in septic shock was considered doubtful, because according to the results of previous studies, both beneficial and deleterious effects were noted with the use of the drug. Later, it was suggested that additional corticosteroid therapy had a beneficial effect on patients with septic shock who had adrenocortical insufficiency. However, regular use of GCS in septic shock is not recommended. The results of a systematic review of the use of the drug in short courses in high doses do not support the possibility of their use in this mode. However, according to meta-analysis and systematic review, the use of corticosteroids with longer courses (5-11 days) at low doses can reduce mortality, especially in patients with vasopressor-dependent septic shock.

    - Patients receiving immunosuppressive doses of methylprednisolone are advised to administer live or live attenuated vaccines. Such patients can be injected with killed or inactivated vaccines; However, the response to the introduction of such vaccines can be reduced. Patients receiving treatment with methylprednisolone in doses that do not have immunosuppressive action can be immunized according to appropriate indications.

    - The use of DEPO-MEDROL® with active tuberculosis is indicated only in cases of focal or disseminated tuberculosis, when methylprednisolone is used in combination with appropriate anti-tuberculosis chemotherapy. If methylprednisolone is prescribed to patients with latent tuberculosis or during the period of tubular tests, the dose should be selected especially carefully. may occur reactivation of the disease. During prolonged therapy with methylprednisolone, such patients should receive anti-tuberculosis chemoprophylaxis.

    - Perhaps the development of allergic reactions. Since in patients receiving methylprednisolone therapy, in rare cases, the development of an anaphylactic reaction is possible,Appropriate precautions should be taken before administration, especially if the patient has had an allergic reaction to a drug in an anamnesis.

    - The use of methylprednisolone can lead to an increase in the concentration of glucose in the blood plasma, worsening of the current diabetes. Patients receiving long-term therapy with DEPO-MEDROL® may have a predisposition to developing diabetes.

    - Against the background of methylprednisolone therapy, various psychiatric disorders can develop: from euphoria, insomnia, mood swings, personality disorders and severe depression to acute psychotic manifestations. In addition, the already existing emotional instability or the tendency to psychotic reactions may become aggravated.

    - Potentially severe mental disorders can occur when systemic forms of methylprednisolone are used. Symptoms usually appear within a few days or weeks after the start of therapy. Most reactions disappear either after a dose reduction or after the drug is discontinued. Despite this, specific treatment may be required.

    - It was reported about psychological violations against the background of the withdrawal of the drug DEPO-MEDROL®, their frequency is unknown. Patients and / or their relatives should be warned that if there is a change in the patient's psychological status (especially with the development of a depressive state and suicidal attempts) it is necessary to seek medical help. Also, patients or their relatives should be warned about the possibility of developing mental disorders during or immediately after lowering the dose of the drug or completely canceling it.

    - With intra-articular injection of methylprednisolone, both systemic and local side effects can occur.

    - It is necessary to conduct an appropriate study of aspirated joint fluid to exclude the septic process.

    - A significant increase in pain accompanied by local swelling, further restriction of joint movements, fever and soreness are signs of septic arthritis. If this complication develops and the diagnosis of sepsis is confirmed, the local administration of methylprednisolone should be discontinued and adequate antimicrobial therapy should be prescribed.

    - You can not enter methylprednisolone in a joint in which there was an infectious process earlier.

    - Methylprednisolone can not be injected into unstable joints.

    - It is necessary to observe the rules of aseptic and antiseptic for the prevention of infections and infection.

    - It should be borne in mind that the absorption of methylprednisolone with intramuscular injection is slower.

    - With intra-articular injection of methylprednisolone, systemic side effects can occur.

    - Although controlled clinical trials have shown that methylprednisolone effectively accelerates the recovery process with exacerbation of multiple sclerosis, it is not established that methylprednisolone affects the outcome and the pathogenesis of the disease. Studies have also shown that in order to achieve a significant effect, it is necessary to administer sufficiently high doses of methylprednisolone.

    - There are reports of the development of epidural lipomatosis in patients receiving methylprednisolone. It usually develops with prolonged therapy with high doses.

    - Since the severity of complications in the treatment of methylprednisolone depends on the dose and duration of therapy, in each case, the potential risk and the expected positive effect should be compared with the choice of dose and duration of treatment,and also when choosing between daily administration and the introduction of a discontinuous course.

    - Cases of crises (including fatal) were reported in patients with pheochromocytoma receiving systemic therapy with GCS, including methylprednisolone. In patients with suspected pheochromocytoma or confirmed disease DEPO-MEDROL® It should be used only after a thorough assessment of the risk / benefit ratio.

    - It is reported that in patients receiving methylprednisolone therapy, Kaposi's sarcoma was noted. However, when methylprednisolone is canceled, clinical remission may occur.

    - There is no evidence that methylprednisolone has a carcinogenic or mutagenic effect or affects reproductive function.

    - DEPO-MEDROL® therapy can mask the symptoms of peptic ulceration and in this case perforation or bleeding can develop without a significant pain syndrome. SCS therapy can mask the symptoms of peritonitis, as well as other signs and symptoms associated with abnormal GI function, such as perforation, obstruction and pancreatitis. At simultaneous application with NSAIDs the risk of formation of gastrointestinal ulcers increases.

    - There are reports of the development of reversible liver damage, which is stopped on the background of the abolition of therapy. In this regard, appropriate monitoring should be carried out.

    - There is an increase in the effect of GCS in patients with cirrhosis due to reduced metabolism of corticosteroids.

    - Reported cases of thrombosis, including venous thromboembolism, with the use of GCS. Therefore, SCS should be used with caution in patients suffering from or having a predisposition to thromboembolic complications.

    - Such adverse reactions of DEPO-MEDROL® from the cardiovascular system, such as dyslipidemia, increase in blood pressure, can provoke new reactions in predisposed patients in case of high doses of DEPO-MEDROL® and long-term treatment. In this regard, should be taken with caution methylprednisolone in patients predisposed to cardiovascular disease and pay special attention to additional monitoring of the state of the cardiovascular system.

    - In patients with chronic heart failure, the drug DEPO-MEDROL® requires compliance with precautionary measures and should be appointed only in absolute indications.

    - The use of GCS in patients with Cushing's disease is not recommended.

    - The use of methylprednisolone in high doses can lead to the development of acute pancreatitis.

    - Acute myopathy most often develops when high doses of methylprednisolone are used in patients with impaired neuromuscular transmission (eg, with myasthenia gravis gravis), or in patients simultaneously receiving treatment with anticholinergic drugs, such as peripheral muscle relaxants (for example, pancuronium bromide). Such acute myopathy has a generalized character, it can affect the muscles of the eye and respiratory system, lead to the development of tetraparesis. It is possible to increase the activity of creatine kinase. In this case, the improvement or recovery after methylprednisolone cancellation can occur only after many weeks or even several years.

    - With prolonged use of large doses of GCS, a common but rarely recognized side effect is osteoporosis.

    - On the background of SCS therapy, there is a high risk of osteoporosis in elderly patients (especially in postmenopausal women).

    - SCS should not be used systematically for traumatic brain damage. There was an increase in mortality in 2 weeks or 6 months after head trauma in patients treated with parenteral forms of SCS. Causation of deaths with the use of methylprednisolone sodium succinate is not established.

    - When using DEPO-MEDROL®, there is an increase in blood pressure, fluid and sodium retention in the body, loss of potassium, hypokalemic alkalosis. These effects are less pronounced when using synthetic derivatives, except for cases when they are used in large doses. Perhaps, it may be necessary to limit consumption of table salt and increase the consumption of products containing potassium. It should be borne in mind that all GCSs increase the excretion of calcium.

    Effect on the ability to drive transp. cf. and fur:

    Systematically, the effect of methylprednisolone on the ability to drive vehicles and mechanisms has not been studied. Against the backdrop of the use of methylprednisolone, there may be such adverse reactions as dizziness, vertigo, visual impairment and weakness.In the event that any of the listed adverse reactions occur in the patient, he should abandon the management of vehicles or mechanisms.

    Form release / dosage:Suspension for injection, 40 mg / ml.
    Packaging:

    1 ml or 2 ml in a bottle of clear glass class I (Hebrew Pharm.).

    One bottle together with the instruction for use is placed in a cardboard box with the control of the first opening.

    Storage conditions:

    At a temperature 15-25 ° C, out of the reach of children.

    Shelf life:

    5 years.

    Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:П N012327 / 01
    Date of registration:03.04.2011 / 14.01.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium
    Manufacturer: & nbsp
    Representation: & nbspPfizer LtdPfizer LtdUSA
    Information update date: & nbsp23.04.2017
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