Description of the drug MEDROL
GKS. When used systemically, it has anti-inflammatory, antiallergic, desensitizing, antishock, antitoxic and immunosuppressive effects.
When applied externally and locally, the therapeutic activity of methylprednisolone is due to its anti-inflammatory, antiallergic and antiexudative (due to the vasoconstrictor effect) effect.
Its anti-inflammatory activity is 5 times higher than that of hydrocortisone; it has virtually no mineralocorticoid activity.
Suppresses the functions of leukocytes and tissue macrophages. Inhibits the release of interleukin-1, interleukin-2, interferon gamma from lymphocytes and macrophages.
Methylprednisolone suppresses the pituitary release of ACTH (and secondarily the synthesis of endogenous corticosteroids) and β-lipotropin, but does not reduce the level of circulating β-endorphin. Inhibits the secretion of TSH and FSH.
Interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus and stimulates the synthesis of mRNA; the latter induces the formation of proteins (including lipocortin) that mediate cellular effects. Lipocortin inhibits the activity of phospholipase A2, which leads to suppression of the release of arachidonic acid, inhibition of the synthesis of prostaglandins, endoperoxides, leukotrienes, which are factors of inflammation and allergic reactions. Suppresses the release of COX (mainly COX-2), which also helps to reduce the production of prostaglandins.
Helps stabilize lysosomal membranes, thereby reducing the concentration of proteolytic enzymes in the area of inflammation. Reduces capillary permeability due to the release of histamine.
Methylprednisolone has a pronounced dose-dependent effect on the metabolism of proteins, fats and carbohydrates.
Reduces the protein content in plasma (due to globulins) with an increase in the albumin/globulin ratio, increases the synthesis of albumins in the liver and kidneys.
It has a catabolic effect in lymphoid and connective tissue, muscles, adipose tissue, skin, bone tissue. Osteoporosis and Itsenko-Cushing syndrome are the main factors limiting long-term GCS therapy. As a result of the catabolic effect, growth suppression in children is possible.
Stimulates the synthesis of higher fatty acids and TG, redistributes adipose tissue (fat accumulates mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase, which leads to increased flow of glucose from the liver into the blood; stimulates gluconeogenesis.
Retains sodium ions and water in the body, stimulates the excretion of potassium, reduces the absorption of calcium from the gastrointestinal tract, promotes the leaching of calcium from bones, increases the excretion of calcium by the kidneys.
In high doses, methylprednisolone can increase the excitability of brain tissue and help lower the seizure threshold.
The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and organelle membranes (especially lysosomal ones).
The antiallergic effect develops as a result of suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in circulating lymphocytes (T- and B-cells) , mast cells, decreased sensitivity of effector cells to allergy mediators, inhibition of antibody production, changes in the body’s immune response.
In COPD, the action is based mainly on inhibition of inflammatory processes, inhibition of development or prevention of swelling of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of β-adrenergic receptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by inhibiting or reducing its production.
Antishock and antitoxic effects are associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenergic receptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane protective properties, and activation of liver enzymes involved in the metabolism of endo- and xenobiotics.
The immunosuppressive effect is due to inhibition of the release of cytokines (interleukin-1, interleukin-2), interferon gamma from lymphocytes and macrophages.
Suppresses fibroblast activity and collagen formation, reduces the possibility of scar tissue formation.
Stimulates excess production of hydrochloric acid and pepsin in the stomach, which increases the risk of developing peptic ulcers.
Medrol®
— Since the complications of methylprednisolone therapy depend on the dose and duration of treatment, in each specific case, based on an analysis of the risk/benefit ratio, a decision is made on the need for such treatment, and the duration of treatment and frequency of administration are also determined.
- The minimum effective dose of the drug should be used to ensure a sufficient therapeutic effect; if necessary, the dose should be reduced gradually.
— During therapy with methylprednisolone, the development of various mental disorders is possible: from euphoria, insomnia, mood instability, personality changes and severe depression to acute psychotic manifestations. In addition, existing emotional instability or psychotic tendencies may be exacerbated.
— Potentially severe mental disorders may occur when using MEDROL®. Symptoms usually appear within a few days to weeks after starting therapy. Most reactions disappear either after reducing the dose or after discontinuation of the drug. Despite this, specific treatment may be required. Psychological effects have been reported in association with methylprednisolone discontinuation; the frequency of these effects is not known.
— Patients and/or their relatives should be warned that if changes occur in the patient’s psychological status (especially with the development of depression and suicidal attempts), it is necessary to seek medical help. Patients or their relatives should also be warned about the possibility of developing mental disorders during or immediately after reducing the dose of the drug or completely stopping it.
- For patients who may be exposed to stress during methylprednisolone therapy, an increase in the dose of the drug before, during and after a stressful situation is indicated.
— Although controlled clinical studies have shown that methylprednisolone is effective in accelerating the recovery process during exacerbation of multiple sclerosis, it has not been established that methylprednisolone affects the outcome and pathogenesis of this disease.
Studies have also shown that sufficiently high doses of methylprednisolone must be administered to achieve a significant effect.
— There are reports of the development of epidural lipomatosis in patients receiving methylprednisolone. Usually with long-term therapy at high doses.
- In patients receiving immunosuppressive doses of methylprednisolone, live or live attenuated vaccines are contraindicated, but killed or inactivated vaccines can be administered, although the response to such vaccines may be reduced. Patients receiving treatment with methylprednisolone in doses that do not have an immunosuppressive effect may be immunized according to appropriate indications.
— During therapy with methylprednisolone, some infections may occur in an erased form, in addition, new infections may develop. When using methylprednisolone, it is possible to reduce resistance to infections, and also reduce the body's ability to localize the infectious process. The development of infections caused by various pathogenic organisms, such as viruses, bacteria, fungi, protozoa or helminths, which are localized in various systems of the human body, may be associated with the use of methylprednisolone, both as monotherapy and in combination with other immunosuppressants affecting cellular immunity, humoral immunity or neutrophil function. These infections can be mild, but in some cases they can be severe and even fatal. Moreover, the higher doses of methylprednisolone are used, the higher the likelihood of developing infectious complications.
— The use of MEDROL® in active tuberculosis should be limited to cases of fulminant and disseminated tuberculosis, when GCS are used to treat the disease in combination with appropriate anti-tuberculosis chemotherapy. If the drug is prescribed to patients with latent tuberculosis or with positive tuberculin tests, then treatment should be carried out under strict medical supervision, since reactivation of the process is possible. During long-term treatment with methylprednisolone, such patients should receive appropriate prophylactic treatment.
— The drug should be used with caution in case of eye damage caused by the herpes simplex virus, due to possible perforation of the cornea.
- GCS, including methylprednisolone, can lead to an increase in blood glucose concentrations, worsen the course of existing diabetes mellitus and, with long-term therapy, can lead to a predisposition to diabetes mellitus.
- Long-term use of methylprednisolone can lead to the occurrence of posterior subcapsular cataracts, glaucoma with possible damage to the optic nerve and provoke the addition of a secondary ocular fungal or viral infection.
- Methylprednisolone therapy can lead to the development of central serous chorioretinopathy, which in turn can lead to retinal detachment.
— Children receiving long-term therapy with MEDROL® are at increased risk of developing intracranial hypertension.
- The use of high doses of methylprednisolone can lead to the development of pancreatitis in children.
- Allergic reactions (for example, angioedema) may develop. When using methylprednisolone, precautions should be taken, especially in patients with a history of allergic reactions to drugs.
— The drug contains lactose produced from cow's milk. Caution should be exercised in patients with known or suspected hypersensitivity to cow's milk or its components or other dairy products as they may contain trace amounts of dairy ingredients.
- Medium and large doses of hydrocortisone or cortisone may cause increased blood pressure, sodium and water retention, and increased potassium excretion. These effects are less likely when using synthetic corticosteroids (including methylprednisolone), except when they are used in high doses. It is necessary to limit the consumption of table salt with food and prescribe potassium supplements. All corticosteroids increase calcium excretion.
— Systemic corticosteroids, including the drug MEDROL®, are not indicated and should not be used for the treatment of traumatic brain injury. An increase in mortality was found at 2 weeks or 6 months after head injury in patients treated with methylprednisolone sodium succinate. There was no direct association with administration of methylprednisolone sodium succinate.
— Osteoporosis is a common and, at the same time, rarely diagnosed adverse reaction that develops with long-term use of high doses of methylprednisolone.
- Children receiving the drug for a long time daily, several times a day, may experience growth retardation, so this dosage regimen should be used only for absolute indications. The use of alternative therapy can usually avoid or minimize this adverse reaction. When using MEDROL® in children, patients should be carefully monitored for normal growth and development.
- Manifestations of secondary adrenal insufficiency that develop during methylprednisolone therapy can be minimized by gradually reducing the dose. This type of relative deficiency may persist for several months after the end of treatment, so methylprednisolone should be reintroduced during this period in any stressful situations. Since the secretion of mineralocorticosteroids may be impaired, electrolytes and/or mineralocorticosteroids should be administered simultaneously.
— There is a more pronounced effect of methylprednisolone in patients with hypothyroidism and cirrhosis of the liver.
— Patients receiving drugs that suppress the immune system are more susceptible to infections than healthy people. For example, chickenpox and measles may be more severe and even fatal in unimmunized children or in adults receiving MEDROL®.
— There is no consensus on the likelihood of developing peptic ulcers during methylprednisolone therapy. Methylprednisolone therapy may mask the symptoms of a peptic ulcer, which may result in perforation or bleeding without significant pain. GCS therapy may mask symptoms of peritonitis, as well as other signs and symptoms associated with gastrointestinal dysfunction, such as perforation, obstruction and pancreatitis. When used simultaneously with NSAIDs, the risk of gastrointestinal ulcers increases.
- The use of methylprednisolone in high doses can lead to the development of acute pancreatitis.
— There are reports of the development of reversible liver damage, which is relieved by discontinuation of therapy. In this regard, appropriate monitoring should be carried out.
— Undesirable reactions of the drug MEDROL® from the cardiovascular system, such as dyslipidemia, increased blood pressure, can provoke new reactions in predisposed patients when using high doses of the drug MEDROL® and long-term treatment. In this regard, methylprednisolone should be taken with caution in patients predisposed to cardiovascular diseases and special attention should be paid to additional monitoring of the state of the cardiovascular system.
- Cases of thrombosis, including venous thromboembolism, have been reported with the use of GCS. Therefore, GCS should be used with caution in patients with current thromboembolic complications or who are predisposed to developing these complications.
- Methylprednisolone should be prescribed with caution for ulcerative colitis, if there is a threat of perforation of the walls of the gastrointestinal tract, the development of an abscess or other purulent infection, as well as for diverticulitis, in the presence of fresh intestinal anastomoses, with active or latent peptic ulcers, renal failure, arterial hypertension, osteoporosis, myasthenia gravis.
— Cases (including fatalities) of the development of crises have been reported in patients suffering from pheochromocytoma receiving systemic therapy with corticosteroids, including methylprednisolone. In patients with suspected or confirmed pheochromocytoma. Methylprednisolone should only be used after a careful risk/benefit assessment.
— There have been cases of the development of Kaposi's sarcoma in patients receiving methylprednisolone therapy (if they are discontinued, clinical remission may occur).
— The effectiveness of MEDROL® in septic shock is questionable. The results of a systematic review of the use of the drug in short courses at high doses do not support its use in this regimen. However, it is assumed that the use of MEDROL® in long courses (5-11 days) in low doses may reduce mortality.
— When using the drug MEDROL® in therapeutic doses for a long period, suppression of the hypothalamic-pituitary-adrenal system (secondary adrenocortical insufficiency) may develop. The degree and duration of adrenocortical insufficiency are individual for each patient and depend on the dose, frequency of use, 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 (see section “Method of administration and dosage”),
— In addition, the development of acute adrenal insufficiency, leading to death, is possible with abrupt discontinuation of the drug MEDROL®. Caution is warranted in patients with systemic scleroderma as an increased incidence of acute scleroderma nephropathy has been observed when taking corticosteroids, including methylprednisolone.
- Since methylprednisolone may enhance the clinical manifestations of Cushing's syndrome, the use of methylprednisolone should be avoided in patients with Cushing's disease.
— Acute myopathy most often develops with the use of high doses of methylprednisolone in patients with impaired neuromuscular transmission (for example, with myasthenia gravis), or in patients simultaneously receiving anticholinergic drugs, such as peripheral muscle relaxants (for example, pancuronium bromide). Such acute myopathy is generalized in nature, can affect the muscles of the eye and respiratory system, and lead to the development of tetraparesis. Creatine kinase levels may be elevated. However, improvement or recovery after discontinuation of methylprednisolone may occur only after many weeks or even several years.
- Withdrawal syndrome, apparently not related to adrenal insufficiency, can also occur due to abrupt discontinuation of the drug MEDROL®. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, skin peeling, myalgia, weight loss and/or decreased blood pressure. It is assumed that these effects occur due to sharp fluctuations in the concentration of methylprednisolone in the blood plasma, and not due to a decrease in the concentration of methylprednisolone in the blood plasma.
— The carcinogenic and mutagenic effects of the drug, as well as its adverse effects on reproductive functions, have not been established.
Solu-medrol®
Since complications of therapy with Solu-Medrol® depend on the dose and duration of treatment, in each specific case, based on an analysis of the risk/benefit ratio, a decision is made on the need for such treatment, and the duration of treatment and frequency of administration are determined.
In order to better control the patient's condition, the lowest dose of Solu-Medrol® should be used. When an effect is achieved, if possible, the dose should be gradually reduced to a maintenance dose or treatment should be discontinued.
Due to the danger of developing arrhythmia, the use of the drug Solu-medrol® in high doses should be carried out in a hospital environment equipped with the necessary equipment (electrocardiograph, defibrillator).
If prolonged spontaneous remission occurs, treatment should be discontinued.
During long-term treatment, the patient should undergo regular examination (chest x-ray, plasma glucose concentration 2 hours after meals, urinalysis, blood pressure, body weight control, preferably an x-ray or endoscopic examination if there is a history of gastrointestinal ulcers). intestinal tract).
The growth and development of children on long-term therapy with Solu-Medrol® should be carefully monitored. Growth retardation may occur in children receiving long-term, daily, multi-dose therapy. This therapy should only be used in the most urgent cases. Taking the drug every other day may reduce the risk of developing this side effect or avoid it altogether.
Children receiving long-term therapy with Solu-Medrol® are at increased risk of developing intracranial hypertension.
The drug Solu-medrol® should also be prescribed with great caution to patients with confirmed or suspected parasitic infections, such as stroigyloidosis. Immunosuppression caused by methylprednisolone in such patients leads to strongyloid hyperinfection and dissemination of the process with widespread migration of larvae, often with the development of severe forms of enterocolitis and gram-negative septicemia with possible death.
Patients receiving drugs that suppress the immune system are more susceptible to infections than healthy individuals. For example, chickenpox and measles may be more severe and even fatal in unimmunized children or in adults receiving Solu-Medrol®. The effectiveness of Solu-Medrol® in septic shock is questionable. The results of a systematic review of the use of the drug in short courses at high doses do not support its use in this regimen. However, it is assumed that the use of Solu-Medrol® in long courses (5-11 days) in low doses may reduce mortality.
Patients who may be exposed to stress during therapy with Solu-Medrol® are advised to increase the dose of the drug before, during and after a stressful situation.
Due to the fact that an increase in mortality was found at 2 weeks or 6 months after head injury in patients treated with methylprednisolone sodium succinate compared with placebo, Solu-Medrol® should not be used for cerebral edema due to head injury. The causal relationship of deaths with the use of methylprednisolone sodium succinate has not been established.
During therapy with Solu-Medrol®, susceptibility to infections may increase, some infections may occur in an erased form, and new infections may develop. In addition, the body’s ability to localize the infectious process is reduced. The development of infections caused by various pathogenic organisms, such as viruses, bacteria, fungi, protozoa or helminths, which are localized in various systems of the human body, may be associated with the use of Solu-Medrol® both as monotherapy and in combination with other immunosuppressants , affecting cellular immunity, humoral immunity or neutrophil function. These infections may not be severe, but in some cases they can be severe and even fatal. Moreover, the higher doses of the drug are used, the higher the likelihood of developing infectious complications.
In patients receiving treatment with Solu-Medrol® in doses that have an immunosuppressive effect, the administration of live or live attenuated vaccines is contraindicated, but killed or inactivated vaccines can be administered, however, the response to the administration of such vaccines may be reduced or even absent. Patients receiving treatment with Solu-Medrol® in doses that do not have an immunosuppressive effect may be immunized according to appropriate indications.
The use of Solu-Medrol® in active tuberculosis should be limited to cases of fulminant and disseminated tuberculosis, when Solu-Medrol® is used to treat the disease in combination with appropriate anti-tuberculosis chemotherapy.
If the drug Solu-Medrol® is prescribed to patients with latent tuberculosis or with positive tuberculin tests, then treatment should be carried out under strict medical supervision, since reactivation of the disease is possible. During long-term drug therapy, such patients should receive appropriate preventive treatment.
Kaposi's sarcoma has been reported in patients treated with Solu-Medrol®. When the drug is discontinued, clinical remission may occur.
Since patients receiving parenteral therapy with Solu-Medrol® may, in rare cases, develop skin reactions and anaphylactic/anaphylactoid reactions, appropriate preventive measures should be taken before administering the drug, especially if the patient has a history of allergic reactions to any medications.
When using the drug Solu-medrol® in therapeutic doses for a long period, suppression of the HPA system (secondary adrenocortical insufficiency) may develop. The degree and duration of adrenocortical insufficiency are individual for each patient and depend on the dose, frequency of use, 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 deficiency may continue for several months after the end of treatment, so in case of any stressful situations during this period, Solu-Medrol® should be re-prescribed. Since the secretion of myeralocorticosteroids may be impaired, concomitant administration of electrolytes and/or myeralocorticosteroids is necessary.
In addition, the development of acute adrenal insufficiency, leading to death, is possible with abrupt discontinuation of the drug Solu-medrol®.
Withdrawal syndrome, which does not appear to be related to adrenal insufficiency, can also occur due to abrupt discontinuation of Solu-Medrol®. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, skin peeling, myalgia, weight loss and/or low blood pressure. It is assumed that these effects occur due to sharp fluctuations in the concentration of methylprednisolone in the blood plasma, and not due to a decrease in the concentration of methylprednisolone in the blood plasma.
In patients with hypothyroidism or cirrhosis, an increased effect of Solu-Medrol® is observed.
The use of Solu-Medrol® may lead to an increase in the concentration of glucose in the blood plasma and a worsening of existing diabetes mellitus. Patients receiving long-term therapy with Solu-Medrol® may be predisposed to the development of diabetes mellitus.
During therapy with Solu-Medrol®, the development of various mental disorders is possible: from euphoria, insomnia, mood instability, personality changes and severe depression to acute psychotic manifestations. In addition, existing emotional instability or psychotic tendencies may be exacerbated.
Potentially severe mental disorders may occur when using Solu-Medrol®. Symptoms usually appear within a few days to weeks after starting therapy. Most reactions disappear either after reducing the dose or after discontinuation of the drug. Despite this, specific treatment may be required.
Patients and/or their relatives should be warned that if changes occur in the patient's psychological status (especially with the development of depression and suicidal attempts), they should seek medical help. Patients or their relatives should also be warned about the possibility of developing mental disorders during or immediately after reducing the dose of the drug or completely stopping it.
Long-term use of the drug Solu-medrol® can lead to the occurrence of posterior subcapsular cataracts and nuclear cataracts (especially in children), exophthalmos or glaucoma with possible damage to the optic nerve and provoke the addition of a secondary ocular fungal or viral infection.
When using the drug Solu-medrol®, there is an increase in blood pressure, fluid and salt retention in the body, loss of potassium, and hypokalemic alkalosis. These effects are less pronounced when using synthetic derivatives, except when used in large doses. You may need to limit your intake of salt and foods containing potassium.
Therapy with Solu-Medrol® may mask the symptoms of a peptic ulcer, in which case perforation or bleeding may develop without significant pain.
Adverse reactions of the drug Solu-medrol® from the cardiovascular system, such as dyslipidemia, increased blood pressure, can provoke new reactions in predisposed patients when using high doses of the drug Solu-medrol® and long-term treatment. In this regard, the drug Solu-Medrol® should be used with caution in patients with risk factors for cardiovascular diseases. Regular monitoring of cardiac function is necessary. Using low doses of Solu-Medrol® every other day may reduce the severity of these side effects.
Impact on the ability to drive vehicles and machinery
Due to the possibility of developing dizziness, blurred vision and weakness, when using the drug Solu-medrol®, persons driving vehicles and engaging in activities that require increased concentration and rapid motor reaction should be careful.
Medrol tablets 32 mg 20 pcs.
Infectious and parasitic diseases: opportunistic infection, infection, masking of infection, activation of latent infection, peritonitis*. Blood and lymphatic system disorders: leukocytosis. Metabolic and nutritional disorders: metabolic acidosis, sodium retention, fluid retention, increased potassium excretion from the body and hypokalemic alkalosis, negative nitrogen balance due to protein catabolism, dyslipidemia, impaired glucose tolerance, increased need for insulin or oral hypoglycemic agents drugs in patients with diabetes mellitus, lipomatosis, increased appetite (may cause weight gain). Musculoskeletal and connective tissue disorders: arthralgia, myalgia, “steroid” myopathy, muscle weakness, muscle atrophy, neuropathic arthropathy, osteoporosis, osteonecrosis, pathological fractures, growth retardation in children. Gastrointestinal (GIT) disorders: peptic ulcer with possible perforation and bleeding, gastric bleeding, pancreatitis, esophagitis, ulcerative esophagitis, perforation of the intestinal wall, bloating, abdominal pain, diarrhea, dyspepsia, nausea. Disturbances identified during clinical and laboratory studies: increased calcium content in the urine, decreased potassium concentration in the blood plasma, suppressed reactions during skin tests, decreased tolerance to carbohydrates, increased urea concentration in the blood plasma. After treatment with GCS, an increase in the activity of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase in blood plasma was observed. Usually these changes are minor, not associated with any clinical syndromes and are reversible after cessation of treatment. Skin and subcutaneous tissue disorders: angioedema, acne, hirsutism, slow wound healing, petechiae and ecchymoses, thinning and decreased skin strength, erythema, hyperhidrosis, itching, rash, skin atrophy, stretch marks, urticaria. Disorders of the genital organs and breast: menstrual irregularities. Endocrine system disorders: GCS withdrawal syndrome, development of Itsenko-Cushing syndrome, suppression of the pituitary-adrenal system. Mental disorders: inappropriate behavior, affective disorders (including emotional lability, depression, euphoria, drug dependence, suicidal thoughts), anxiety, confusion, insomnia, irritability, mental disorders, mood swings, personality changes, psychotic behavior, psychotic disorders (including mania, delusions, hallucinations and schizophrenia (or exacerbation of schizophrenia)). Nervous system disorders: increased intracranial pressure (with papilledema (benign intracranial hypertension)), pseudotumor cerebri, seizures, amnesia, cognitive impairment, dizziness, headache, epidural lipomatosis. Visual disorders: cataracts, increased intraocular pressure with the risk of damage to the optic nerve, exophthalmos, chorioretinopathy, glaucoma, thinning of the cornea and sclera. Disorders of the hearing and vestibular apparatus: vertigo. Immune system disorders: hypersensitivity reactions (anaphylactic and anaphylactoid reactions). Cardiac disorders: chronic heart failure (in predisposed patients). Vascular system disorders: thrombosis, increased blood pressure, decreased blood pressure, pulmonary embolism. Disorders of the respiratory system, chest and mediastinal organs: hiccups. General disorders and disorders at the injection site: increased fatigue, weakness, peripheral edema, malaise. Injuries, intoxications and complications of manipulation: compression fracture of the spine, aseptic epiphysionecrosis of the cortical bone layer, tendon rupture, in particular the Achilles tendon. * The main and severe complication of diseases of the gastrointestinal tract (perforation of the walls of the stomach and intestines, pancreatitis) is peritonitis.
