Medrol tablets 16 mg blister No. 50

Instructions Medrol tablets 16 mg blister No. 50

Composition

active ingredient: methylprednisolone;

1 tablet contains methylprednisolone 4 mg or 16 mg or 32 mg;

Excipients: tablets containing 4 mg of methylprednisolone – lactose monohydrate; corn starch; sucrose; calcium stearate;

tablets containing 16 mg of methylprednisolone – lactose monohydrate; corn starch; sucrose; calcium stearate; mineral oil;

tablets containing 32 mg of methylprednisolone – lactose monohydrate; corn starch; sucrose; calcium stearate; mineral oil.

Dosage form

Pills.

Main physicochemical properties:

4 mg tablets – white, semi-oval, elliptical tablets with “MEDROL 4” embossed on one side and a cross-shaped notch on the other;

16 mg tablets – white, convex, elliptical tablets with “MEDROL 16” embossed on one side and a cross-shaped score on the other;

32 mg tablets – white, convex, elliptical tablets with a cross-shaped score on one side and marking “UPJOHN 176” on the other.

The cross-shaped score on the tablets is not functional and is not intended to divide the tablet.

Pharmacotherapeutic group

Corticosteroids for systemic use. Glucocorticoids. ATX code H02A B04.

Pharmacological properties

Methylprednisolone is a potent anti-inflammatory steroid. It has more pronounced anti-inflammatory activity and less tendency to retain sodium and water than prednisolone. The relative activity of methylprednisolone and hydrocortisone is at least four to one.

Pharmacodynamics

Methylprednisolone belongs to the group of synthetic glucocorticoids. Glucocorticoids penetrate cell membranes and form complexes with specific cytoplasmic receptors. Then these complexes penetrate the cell nucleus, bind to DNA (chromatin), stimulate mRNA transcription and subsequent protein synthesis of various enzymes, which explains the effect of systemic use of glucocorticoids. 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 muscles and the central nervous system.

Impact on the inflammatory process and immune response.

Most indications for the use of glucocorticoids are due to their anti-inflammatory, immunosuppressive and antiallergic properties. These properties achieve the following therapeutic effects:

- reduction in the number of immunoactive cells near the focus of inflammation;

- reduction of vasodilation;

- stabilization of lysosomal membranes;

- inhibition of phagocytosis;

- reduction in the production of prostaglandins and related compounds.

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

Effect on carbohydrate and protein metabolism.

Glucocorticoids have a catabolic effect on proteins. The released amino acids are converted into glucose and glycogen in the liver by gluconeogenesis. Glucose absorption in peripheral tissues is reduced, which can lead to hyperglycemia and glycosuria, especially in patients predisposed to diabetes.

Effect on fat metabolism.

Glucocorticoids have a lipolytic effect, which is primarily manifested in the tissues of the extremities. Glucocorticoids also have a lipogenetic effect, which is most pronounced in the chest, neck and head. All this leads to the redistribution of fat deposits. The maximum pharmacological activity of corticosteroids is manifested when the peak concentration in the blood plasma has already been passed, therefore it is believed that the vast majority of therapeutic effects of drugs are due primarily to the modification of enzyme activity, rather than the direct action of the drug.

Pharmacokinetics

The pharmacokinetics of methylprednisolone are linear regardless of the route of administration.

Absorption.

Methylprednisolone is rapidly absorbed, and peak plasma concentrations of methylprednisolone in healthy volunteers are reached approximately 1.5–2.3 hours (depending on dose) after oral administration of this medicinal product. The absolute bioavailability of methylprednisolone in healthy volunteers after oral administration is generally high (82–89%).

Distribution.

Methylprednisolone is widely distributed in tissues, crosses the blood-brain barrier and is excreted in breast milk. The apparent volume of distribution of methylprednisolone is approximately 1.4 l/kg. The binding of methylprednisolone to plasma proteins in humans is approximately 77%.

Metabolism.

Methylprednisolone, like many CYP3A4 substrates, can also be a substrate for the ATP-binding cassette (ABC) transport protein P-glycoprotein, which affects its distribution in tissues and interactions with other drugs.

Breeding.

The mean half-life of methylprednisolone is 1.8 to 5.2 hours. Total clearance is approximately 5–6 mL/min/kg.

No dose adjustment is required for patients with renal insufficiency. Methylprednisolone is removed by hemodialysis.

Indication

Endocrine diseases.

Primary and secondary adrenal cortical insufficiency (first-line drugs are hydrocortisone or cortisone; if necessary, synthetic analogues can be used in combination with mineralocorticoids; simultaneous use of mineralocorticoids is especially important for the treatment of young children).

Congenital adrenal hyperplasia.

Non-purulent thyroiditis.

Hypercalcemia in malignant tumors.

Non-endocrine diseases.

Rheumatic diseases.

As an additional therapy for short-term use (to relieve the patient from an acute condition or during exacerbation of the process) for the following 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 in osteoarthritis;

epicondylitis.

Collagenoses.

During the period of exacerbation or in some cases as maintenance therapy for the following diseases:

systemic lupus erythematosus;

systemic dermatomyositis (polymyositis);

acute rheumatic carditis;

polymyalgia rheumatica in giant cell arteritis.

Skin diseases.

Pemphigus;

bullous dermatitis herpetiformis;

severe erythema multiforme (Stevens-Johnson syndrome);

exfoliative dermatitis;

mycosis fungoides;

severe psoriasis;

severe seborrheic dermatitis.

Allergic conditions.

For the treatment of the following severe and disabling allergic conditions when standard treatment is ineffective:

seasonal or perennial allergic rhinitis;

serum sickness;

bronchial asthma;

hypersensitivity reactions to drugs;

contact dermatitis;

atopic dermatitis.

Eye diseases.

Severe acute and chronic allergic and inflammatory processes affecting the eyes and adnexa, such as:

allergic marginal corneal ulcers;

eye damage caused by Herpes zoster;

inflammation of the anterior segment of the eye;

diffuse posterior uveitis and choroiditis;

sympathetic ophthalmia;

allergic conjunctivitis;

keratitis;

chorioretinitis;

optic neuritis;

iritis and iridocyclitis.

Respiratory diseases.

Symptomatic sarcoidosis;

Leffler syndrome, which is not amenable to treatment by other methods;

berylliosis;

fulminant or disseminated pulmonary tuberculosis (used in combination with appropriate anti-tuberculosis chemotherapy);

aspiration pneumonitis.

Hematological 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 for the following diseases:

leukemia and lymphoma in adults;

acute leukemia in children.

Edema syndrome.

For induction of diuresis or elimination of proteinuria in nephrotic syndrome without uremia, idiopathic type or caused by systemic lupus erythematosus.

Diseases of the digestive tract.

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

ulcerative colitis;

Crohn's disease.

Diseases of the nervous system.

Multiple sclerosis in the exacerbation phase;

brain swelling caused by a brain tumor.

Diseases of other organs and systems.

Tuberculous meningitis with subarachnoid block or at risk of developing a block, in combination with appropriate anti-tuberculosis chemotherapy;

trichinosis with damage to the nervous system or myocardium.

Organ transplantation.

Contraindication

- Systemic fungal infections.

- Systemic infections in cases where specific antimicrobial therapy is not prescribed.

- Hypersensitivity to methylprednisolone or to the components of the drug listed in the "Composition" section.

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Interaction with other medicinal products and other types of interactions

CYP3A4 inhibitors – Drugs that inhibit CYP3A4 activity tend to decrease hepatic clearance and increase plasma concentrations of drugs that are CYP3A4 substrates, such as methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity. CYP3A4 inhibitors include grapefruit juice; the macrolide antibiotic troleandomycin; and the pharmacokinetic enhancer cobicistat.

CYP3A4 inducers – drugs that stimulate CYP3A4 activity, as a rule, increase hepatic clearance, which leads to a decrease in plasma concentrations of drugs that are CYP3A4 substrates. When these drugs are used simultaneously, an increase in the dose of methylprednisolone may be required to achieve the desired effect. Such drugs include the antibacterial and anti-tuberculosis drug rifampicin; anticonvulsants phenobarbital, phenytoin.

CYP3A4 substrates - the presence of another CYP3A4 substrate may affect the hepatic clearance of methylprednisolone, requiring appropriate dose adjustment. Adverse reactions associated with the use of one of these drugs as monotherapy may be more likely when they are used concomitantly. These include the immunosuppressants cyclophosphamide, tacrolimus.

Results of interactions with other drugs (that are not CYP3A4 enzymes) – other interactions and their results are described in the table below.

List and description of the most frequent and/or clinically important interactions or results of interactions of methylprednisolone with other drugs.

Application features

Immunosuppressive effects/increased susceptibility to infections.

Corticosteroids may increase susceptibility to infections; they may mask some of the symptoms of infections; and new infections may develop during corticosteroid therapy. Resistance to infections may be reduced with the use of corticosteroids and the body may be unable to control infection. Infections caused by any agent, including viruses, bacteria, fungi, protozoa, or helminths, in any part of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressants that affect cellular immunity, humoral immunity, or neutrophil function. These infections may be mild, but they may also be severe and, in some cases, fatal. The incidence of infectious complications increases with increasing corticosteroid doses.

Patients taking medications that suppress the immune system are more susceptible to infections than healthy people. Chickenpox and measles, for example, can have more serious or even fatal consequences in unimmunized children or adults taking corticosteroids.

The use of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids is contraindicated. Patients receiving immunosuppressive doses of corticosteroids may be vaccinated with killed or inactivated vaccines, but their response to such vaccines may be attenuated. These immunization procedures may be performed in patients receiving non-immunosuppressive doses of corticosteroids.

The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated tuberculosis and should be combined with appropriate antituberculosis therapy. If corticosteroids are indicated in patients with latent tuberculosis or with a negative tuberculin test, treatment should be carried out under close supervision, since reactivation of the disease is possible. During prolonged corticosteroid therapy, such patients should receive chemoprophylactic drugs.

Cases of Kaposi's sarcoma have been reported in patients receiving corticosteroid therapy. In such cases, discontinuation of corticosteroid therapy may result in clinical remission.

There is no consensus on the role of corticosteroids in the treatment of patients with septic shock. Early studies reported both positive and negative effects of corticosteroids in this clinical setting. Later studies have suggested that corticosteroids as adjunctive therapy have a beneficial effect in patients with established septic shock who have adrenal insufficiency. However, routine use of these agents in patients with septic shock is not recommended. A systematic review of the evidence following short courses of high-dose corticosteroids in such patients concluded that there is no evidence to support their use. However, a meta-analysis and one review have suggested that longer (5–11 days) courses of low-dose corticosteroids may reduce mortality, particularly in patients with septic shock who require vasopressor therapy.

Impact on the immune system.

Allergic reactions (e.g. angioedema) may occur. Skin reactions and anaphylactic/anaphylactoid reactions have been reported rarely in patients receiving corticosteroid therapy; appropriate precautions should be taken before using corticosteroids, especially if the patient has a history of allergy to any drug.

The medicinal product contains lactose derived from cow's milk. Patients with known or suspected hypersensitivity to cow's milk protein, its components or other dairy products should be cautious as the medicinal product may contain trace elements of dairy components.

Impact on the endocrine system.

Corticosteroids used for a long period of time in pharmacological doses may lead to suppression of the hypothalamic-pituitary-adrenal axis (secondary adrenocortical insufficiency). The degree and duration of adrenocortical insufficiency vary in different patients and depend on the dose, frequency, time of administration, and duration of glucocorticoid therapy. This effect can be minimized by the use of alternating therapy (see section "Method of administration and dosage").

Sudden withdrawal of glucocorticoids can lead to acute adrenal insufficiency, which can be fatal.

Adrenocortical insufficiency caused by the administration of the drug can be minimized by gradually reducing the dose. This type of relative insufficiency can persist for months after discontinuation of therapy; therefore, if any stressful situation occurs during this period, hormone therapy should be resumed. Since a negative effect on mineralocorticoid secretion is possible, mineralocorticoids and/or salt intake should be used concomitantly.

After abrupt cessation of glucocorticoids, a steroid withdrawal syndrome may also develop, seemingly unrelated to adrenal insufficiency. Symptoms of this syndrome include anorexia, nausea, vomiting, lethargy, headache, fever, arthralgia, desquamation, myalgia, weight loss, and/or hypotension. These effects are thought to be due to the abrupt change in glucocorticoid concentrations rather than to low corticosteroid levels.

Since glucocorticoids may cause or exacerbate Cushing's syndrome, their use should be avoided in patients with Cushing's disease.

A more pronounced effect of corticosteroids is noted in patients with hypothyroidism.

Metabolic and nutritional disorders.

Corticosteroids, including methylprednisolone, may increase blood glucose levels, worsen the condition of patients with pre-existing diabetes, and predispose patients to diabetes mellitus who use corticosteroids long-term.

Mental disorders.

Corticosteroids can cause a variety of psychiatric disorders, from euphoria, insomnia, mood swings, personality changes, and severe depression to severe psychotic manifestations. In addition, corticosteroids may exacerbate pre-existing emotional instability and psychotic reactions.

Potentially serious psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms usually occur within a few days to weeks of initiating therapy. Most reactions resolve after dose reduction or discontinuation, although specific treatment may be required. Psychiatric reactions have been reported to occur with corticosteroid withdrawal; the frequency is unknown. Patients and caregivers should be advised to seek medical advice if any psychiatric disorder develops, particularly if depressed mood or suicidal ideation is suspected. Patients and caregivers should be alert to possible psychiatric disorders that may occur during or immediately after tapering or discontinuing systemic steroids.

Increasing the dose of rapid-acting corticosteroids before, during, and after a stressful situation is indicated for patients taking corticosteroids and exposed to an unusual stressful situation.

Nervous system disorders.

Corticosteroids should be used with caution in patients with seizures and myasthenia gravis (see information on myopathy in the Musculoskeletal Disorders section of this section).

Although controlled clinical trials have demonstrated the efficacy of corticosteroids in accelerating resolution of multiple sclerosis exacerbations, they have not demonstrated an effect of corticosteroids on the outcome or natural history of the disease. These trials have shown that relatively high doses of corticosteroids are required to achieve a significant effect (see Dosage and Administration).

Epidural lipomatosis has been reported in patients receiving corticosteroids, usually at high doses and over a long period of time.

Disorders of the organs of vision.

In ocular lesions caused by herpes simplex virus, corticosteroids should be used with caution because of the risk of corneal perforation. Prolonged use of corticosteroids may cause posterior subcapsular cataracts and nuclear cataracts (especially in children), exophthalmos, or increased intraocular pressure, which can lead to glaucoma with possible optic nerve damage. Patients receiving glucocorticoids are at increased risk of secondary ocular infections caused by fungi and viruses.

The use of corticosteroids has been associated with the development of central serous chorioretinopathy, which can lead to retinal detachment.

Heart disorders.

Cardiovascular adverse reactions associated with glucocorticoids, such as dyslipidemia and hypertension, may predispose patients with preexisting cardiovascular risk factors to additional cardiovascular effects when used at high doses and in prolonged courses. Therefore, corticosteroids should be used judiciously in such patients, with consideration given to risk factor modification and additional cardiac monitoring as necessary. Low doses and alternating therapy may reduce the incidence of complications with corticosteroid therapy.

In patients with congestive heart failure, systemic corticosteroids should be used with caution and only when absolutely necessary.

Vascular disorders.

Cases of thrombosis, including venous thromboembolism, have been reported with the use of corticosteroids. Therefore, caution should be exercised when prescribing corticosteroids to patients who have or may be predisposed to thromboembolic disorders.

Corticosteroids should be used with caution in patients with hypertension.

Gastrointestinal disorders.

High doses of corticosteroids can cause the development of acute pancreatitis.

There is no consensus on whether corticosteroids cause peptic ulcer disease during therapy. However, glucocorticoid therapy may mask the symptoms of peptic ulcer disease, so perforation or bleeding may occur without significant pain. Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders, such as perforation, obstruction, or pancreatitis. The risk of gastrointestinal ulcers is increased when combined with NSAIDs.

Corticosteroids should be used with caution in nonspecific ulcerative colitis, if there is a risk of perforation, abscess formation, or other purulent infection; in diverticulitis; in the case of recently performed intestinal anastomoses; in active or latent peptic ulcer.

Hepatobiliary system disorders.

Hepatobiliary disorders have been reported and were reversible after drug withdrawal. Therefore, appropriate monitoring is necessary.

Musculoskeletal disorders.

Acute myopathy has been reported with high-dose corticosteroids, most commonly in patients with neuromuscular disorders (e.g. myasthenia gravis) or in patients receiving concomitant anticholinergic therapy such as neuromuscular blocking agents (e.g. pancuronium). This acute myopathy is generalized, may involve the ocular and respiratory muscles, and may result in tetraparesis. Elevated creatine kinase may occur. Clinical improvement or recovery may take several weeks to several years after discontinuation of corticosteroids.

Osteoporosis is a common (but rarely diagnosed) side effect associated with long-term use of high doses of glucocorticoids.

Kidney and urinary system disorders.

Use with caution in patients with systemic scleroderma as an increased incidence of scleroderma renal crisis has been observed with the use of corticosteroids, including methylprednisolone. Corticosteroids should be used with caution in patients with renal insufficiency. Studies.

The use of hydrocortisone or cortisone in moderate to high doses may cause an increase in blood pressure, salt and water retention, and increased potassium excretion. The likelihood of such effects is lower with the synthetic derivatives of these drugs, except when high doses are used. A salt-restricted diet and potassium supplements may be necessary. All corticosteroids increase calcium excretion.

Injuries, poisoning and complications of procedures.

Systemic corticosteroids are not indicated and should not be used in the treatment of traumatic brain injury. A multicenter study found an increase in mortality at 2 weeks and 6 months after injury in patients receiving methylprednisolone compared with those receiving placebo. A causal relationship to methylprednisolone treatment has not been established.

Since complications during treatment with glucocorticoids depend on the dose of the drug and the duration of therapy, in each case, a careful assessment of the ratio of the benefits of using the drug and the potential risk should be carried out when determining both the dose and duration of treatment, as well as the choice of the regimen of use - daily or intermittent.

When treating with corticosteroids, the lowest possible dose that provides sufficient therapeutic effect should be prescribed, and when dose reduction becomes possible, this reduction should be carried out gradually.

Concomitant use with CYP3A inhibitors, including cobicistat-containing products, is thought to increase the risk of systemic adverse reactions. This combination should be avoided unless the benefit outweighs the increased risk of systemic adverse reactions with corticosteroids; in such cases, patients should be monitored for systemic adverse reactions associated with corticosteroids.

Aspirin and nonsteroidal anti-inflammatory drugs should be used with caution in combination with corticosteroids.

Pheochromocytoma crisis, which can be fatal, has been reported following the use of systemic corticosteroids. Corticosteroids should be administered to patients with suspected or established pheochromocytoma only after an appropriate risk/benefit assessment.

During post-marketing surveillance, tumor lysis syndrome (TLS) has been reported in patients with malignancies, including hematological malignancies and solid tumors, following the use of systemic corticosteroids alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as those with tumors with a high proliferation rate, high tumor burden, and high sensitivity to cytotoxic agents, should be closely monitored and appropriate precautions should be taken.

The drug contains lactose monohydrate, so it should not be used in patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome.

The drug contains sucrose, so patients with known intolerance to some sugars should consult their doctor before taking this medicine.

Use during pregnancy or breastfeeding

Pregnancy.

Some animal studies have shown that high doses of corticosteroids administered to pregnant women may cause fetal malformations. Although there is no evidence that corticosteroids cause congenital malformations when administered to pregnant women, the results of studies in pregnant women do not completely exclude fetal harm.

Since adequate studies of the effects of methylprednisolone on human reproductive function have not been conducted, this drug should be prescribed during pregnancy only after careful assessment of the risk/benefit ratio for the mother and fetus.

Some corticosteroids readily cross the placental barrier. One retrospective study reported an increased incidence of low birth weight in infants born to mothers who had taken corticosteroids. In humans, the risk of low birth weight has been found to be dose-related and can be minimized by using lower doses of corticosteroids. Infants whose mothers received relatively high doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency, although this insufficiency is rare in infants exposed to corticosteroids in utero.

The effect of corticosteroids on the course and outcome of labor is unknown.

Cases of cataracts have been observed in infants whose mothers received long-term corticosteroid treatment during pregnancy.

Breastfeeding period.

Corticosteroids pass into breast milk and may suppress growth and affect