Medrol, 32 mg tablets 20 pcs

Medrol is a GCS. Penetrating through cell membranes it forms complexes with specific cytoplasmic receptors. Then these complexes penetrate into the cell nucleus, bind to DNA (chromatin) and stimulate mRNA transcription and subsequent synthesis of various enzymes, which explains the effect of GCS when used systemically. GCS not only have a significant effect on the inflammatory process and immune response, but also affect carbohydrate, protein and fat metabolism. They also affect the cardiovascular system, skeletal muscles and the central nervous system.

The effects on the inflammatory process and immune response. Methylprednisolone (like other GKS) has anti-inflammatory, immunosuppressive and anti-allergic properties. Due to these properties the following therapeutic effects are achieved: reduction of the number of immunoactive cells near the focus of inflammation; reduction of vasodilation; stabilization of lysosomal membranes; inhibition of phagocytosis; reduction of prostaglandin and related compounds production.

Methylprednisolone acetate at a dose of 4.4 mg (4 mg of methylprednisolone) has the same anti-inflammatory effect as hydrocortisone at a dose of 20 mg.

Methylprednisolone has only slight mineralocorticoid activity (200 mg of methylprednisolone is equivalent to 1 mg of deoxycorticosterone).

The effect on carbohydrate and protein metabolism. Methylprednisolone (like other GKS) has a catabolic effect on proteins. Released amino acids are converted into glucose and glycogen during gluconeogenesis in the liver. Glucose uptake in peripheral tissues decreases, which can lead to hyperglycemia and glucosuria, especially in patients at risk of developing diabetes.

The effect on fat metabolism. Methylprednisolone (like other GKS) has lipolytic effects, which are primarily seen in the extremities. It also has a lipogenetic effect, which is most pronounced in the chest, neck and head. All this leads to a redistribution of fat deposits.

The maximum pharmacological activity of GCS is not observed at peak plasma concentrations but only afterwards, therefore GCS activity is primarily determined by the effect on enzyme activity.

Pharmacokinetics

Absorption and distribution

Absorption of methylprednisolone occurs primarily in the proximal small intestine, where it is about 2 times greater than in the distal colon.

The binding of methylprednisolone to proteins (albumin and transcortin) is about 40-90%.

Metabolism

Metabolism of methylprednisolone occurs in the liver and is qualitatively similar to that of cortisol. The main metabolites are 20p-hydroxymethylprednisolone and 20p-hydroxy-6a-methylprednisolone.

Elimation

The metabolites are excreted mainly with the urine in unbound form and also in the form of glucuronides and sulfates, which are formed mainly in the liver and partially in the kidneys.

Methylprednisolone is a GCS with intermediate duration of action. Due to intracellular activity, there is a marked difference between T1/2 from blood plasma (approximately 3.3 hours) and T1/2 from the body as a whole (approximately 12-36 hours). The pharmacotherapeutic effect is maintained even when the level of active substance in blood is no longer determined.

Indications

Endocrine diseases:

Musculoskeletal system diseases (including rheumatic) (as adjunctive therapy for short periods to relieve acute conditions or with exacerbations):

Systemic connective tissue diseases (during exacerbation or in some cases as supportive therapy):

Skin diseases:

Allergic reactions (severe or disabling conditions in which conventional therapy is ineffective):

Eye diseases (severe acute and chronic allergic and inflammatory processes with eye damage):

Active ingredient

Composition

1 tablet contains:

Active ingredient:

methylprednisolone 32 mg;

Associates:

Calcium stearate;

Corn starch;

Lactose;

saccharose.

How to take, the dosage

Ingestion. The dose may vary and should be chosen individually depending on the nature of the disease and the patient’s response to therapy. The initial dose is 4 to 48 mg/day depending on the nature of the disease. In less severe diseases lower doses are usually sufficient, although some patients may require higher doses. High doses may be required for diseases and conditions such as multiple sclerosis (200 mg/day), brain edema (200-1000 mg/day) and organ transplantation (up to 7 mg/kg/day). If a satisfactory clinical effect is not obtained after a sufficient period of time, the drug should be withdrawn and another therapy should be prescribed to the patient.

In children, the dose is determined by the physician with regard to weight or body surface area. In adrenal insufficiency, 0.18 mg/kg or 3.33 mg/m2/day in 3 doses; in other indications, 0.42-1.67 mg/kg or 12.5-50 mg/m2/day in 3 doses.

The withdrawal of the drug after long-term therapy is recommended to be carried out gradually. If a good effect is obtained during treatment, an individual maintenance dose should be selected for the patient by gradually reducing the initial dose at certain intervals until the lowest dose is found to maintain the achieved clinical effect. Keep in mind that continuous monitoring of the drug dosing regimen is necessary.

There may be situations that require dose adjustments, such as changes in clinical presentation with remission and onset of disease, individual patient responses, and distress not directly related to the underlying disease, which may require increasing the dose for a period of time and is dependent on the patient’s condition.

Alternating therapy.

Alternating therapy is a dosing regimen in which twice the daily dose of glucocorticosteroids is given in the morning every other day. The goal of this therapy is to maximize clinical benefit while minimizing some of the adverse effects such as pituitary-adrenal suppression, glucocorticosteroid withdrawal, and growth retardation in children.

Interaction

Increases toxicity of cardiac glycosides (due to the resulting hypokalemia the risk of arrhythmias increases). Accelerates excretion of ASA, reduces its concentration in the blood (when methylprednisolone is withdrawn, the concentration of salicylates in the blood increases and the risk of side effects increases).

When used simultaneously with live antiviral vaccines and against the background of other types of immunizations increases the risk of virus activation and development of infections. Increases metabolism of isoniazid, mexiletine (especially in “fast” acetylators), which leads to a decrease in their plasma concentrations. Increases the risk of hepatotoxic reactions of paracetamol (induction of “liver” enzymes and formation of toxic metabolite of paracetamol).

Enhances (with prolonged therapy) folic acid. Hypokalemia caused by GCS may increase the severity and duration of muscle block against the background of muscle relaxants. In high doses, it reduces the effect of somatropin. Antacids reduce absorption of GCS. Reduces the effect of hypoglycemic drugs, increases the anticoagulant effect of coumarin derivatives. Weakens the effect of vitamin D on Ca2+ absorption in the intestinal lumen.

Ergocalciferol and parathormone prevent the development of osteopathy caused by GCS. Reduces the concentration of praziquantel in the blood. Ketoconazole reduces clearance and increases toxicity of methylprednisolone. Co-administration with cyclosporine causes mutual inhibition of metabolism – risk of side effects of both drugs (cases of seizures were noted when used together).

Tiazide diuretics, carbohydrate inhibitors, etc. GCS and amphotericin B increase the risk of hypokalemia, Na+-containing drugs – edema and increased BP. NSAIDs and ethanol increase the risk of gastrointestinal mucosa ulceration and bleeding, in combination with NSAIDs for arthritis treatment, the dose of GCS may be reduced due to the summation of therapeutic effect. Indomethacin, displacing methylprednisolone from binding to albumin, increases the risk of its side effects.

Amphotericin B and carboanhydrase inhibitors increase the risk of osteoporosis. The therapeutic effect of GCS is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “hepatic” microsomal enzymes (increased metabolic rate). Mitotane and other inhibitors of adrenal cortex function may necessitate increasing the dose of GCS. The clearance of GCS is increased with thyroid hormones.

Immunosuppressants increase the risk of infection and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus. Estrogens (including oral estrogen-containing contraceptives) decrease GCS clearance, prolong T1/2 and their therapeutic and toxic effects.

The appearance of hirsutism and acne is promoted by the simultaneous use of other steroid hormonal drugs – androgens, estrogens, anabolics, oral contraceptives. Tricyclic antidepressants can increase the severity of depression caused by GCS (not indicated for therapy of these side effects). The risk of cataracts increases when used together with other GCSs and antipsychotics. GCS, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.

The simultaneous use with m-cholinoblockers (including antihistamines, tricyclic antidepressants), nitrates promotes development of increased intraocular pressure.

Special Instructions

Before treatment, the patient should be examined for possible contraindications. Clinical examination should include CPS, lung X-ray, gastric and duodenal examination; urinary system, organs of vision.

Before and during steroid therapy, it is necessary to monitor general blood count, blood and urine glucose concentrations, plasma electrolytes. In intercurrent infections, septic conditions and tuberculosis, simultaneous antibiotic therapy is necessary. Immunization should not be carried out during treatment.

In case of sudden withdrawal, especially in case of previous use of high doses, a syndrome of “withdrawal” of GCS occurs: decreased appetite, nausea, lethargy, generalized bone and muscle pain, asthenia. After withdrawal, relative insufficiency of the adrenal cortex persists for several months. If stressful situations occur during this period, GCS is prescribed (as indicated) for a period of time, if necessary – in combination with ICS.

In children who have been in contact with patients with measles or chickenpox during treatment, specific Ig is prescribed prophylactically. To reduce side effects, administration of anabolic steroids and increased intake of K+ with food are justified. In Addison’s disease, concomitant administration of barbiturates should be avoided – the risk of acute adrenal insufficiency (Addison’s crisis).

Application during pregnancy in the first trimester and during lactation: administer with consideration of the expected therapeutic effect and adverse effects on the fetus and child. In case of long-term therapy during pregnancy – fetal growth disorder.

In III trimester of pregnancy – danger of adrenal cortex atrophy in fetus, which may require substitution therapy in a newborn. In children during growth, GCS should be used only with absolute indications and under close supervision of the attending physician.

Contraindications

Hypersensitivity to the drug components.

The drug should be used with caution in gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, intestinal anastomosis (in the immediate history), non-specific ulcerative colitis with risk of perforation or abscess, diverticulitis;

Diabetes mellitus and predisposition to it; hyperlipidemia;

Myasthenia gravis, osteoporosis, hypothyroidism, hyperthyroidism, acute psychosis, acute and subacute myocardial infarction, congestive heart failure, arterial hypertension, severe liver function disorders (especially with associated hypoalbuminemia) or renal disease, open-angle glaucoma, herpes simplex (eye form), chicken pox, measles, strongyloidosis, AIDS, HIV infection;

In active and latent tuberculosis, severe bacterial or viral infectious diseases (increases the risk of superinfection, masks the symptoms of the disease), it is allowed to use the drug only against the background of specific therapy.

In case of systemic fungal infections the drug is not recommended.

Side effects

Metabolic disorders: sodium retention, chronic heart failure in predisposed patients, increased BP, fluid retention, potassium loss and hypokalemic alkalosis, negative nitrogen balance due to protein catabolism.

Muscular system disorders: steroid myopathy, muscle weakness, osteoporosis, pathological fractures, vertebral compression fractures, aseptic necrosis of epiphyses of tubular bones, tendon ruptures, especially of Achilles tendon.

Digestive system disorders: peptic ulcer with possible perforation and bleeding, gastric bleeding, pancreatitis, esophagitis, intestinal perforation. After GCS treatment an increase of serum ALT, ACT and ALP activity was observed. Usually these changes are insignificant, not associated with any clinical syndromes and are reversible after discontinuation of treatment.

Dermatological reactions: slow wound healing, petechiae and ecchymosis, thinning and decreased skin strength.

Nervous system disorders: increased intracranial pressure, pseudotumor of the brain, mental disorders, seizures.

Endocrine system disorders: menstrual cycle disorders, hirsutism, development of Cushing’s syndrome, suppression of pituitary-adrenal system, decreased carbohydrate tolerance, manifestation of latent diabetes, increased need for insulin or oral hypoglycemic agents in diabetic patients, growth retardation in children.

Overlooking organ: posterior subcapsular cataract, increased intraocular pressure with risk of optic nerve damage, exophthalmus.

Allergic reactions: hypersensitivity reactions, including allergic systemic reactions, possible suppression of reactions in skin tests.

Others: Slow clinical picture in infectious diseases, activation of latent infections, the occurrence of infections caused by opportunistic pathogens, withdrawal syndrome of GCS.

Overdose

The clinical syndrome of acute overdose of the drug has not been described. Reports of cases of acute toxicity in GCS overdose are extremely rare.

Symptoms: Frequent repeated administration (daily or several times a week) over a long period of time may lead to the development of Cushing’s syndrome and other complications characteristic of long-term GCS therapy.

Treatment: conduct symptomatic therapy. Methylprednisolone is excreted by dialysis. There is no specific antidote.

Pregnancy use

The use of Medrol during pregnancy is possible if the expected effect of therapy exceeds the potential risk to the fetus (adequate and strictly controlled safety studies have not been conducted).

Women of childbearing age should be warned about the potential risk to the fetus (corticosteroids pass through the placenta).

Feeding women are advised to stop either breastfeeding or the use of the drug, especially in high doses (corticosteroids penetrate into breast milk and may inhibit endogenous corticosteroid production, suppress growth and cause unwanted effects in the offspring).

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