Expiration date: 12/2025

Dosage form

Colorless, slightly viscous liquid containing easily resuspended white particles, free from foreign inclusions.

Composition

1 ml of suspension for injection contains:

Active ingredient:

Betamethasone dipropionate 6.43 mg, equivalent to betamethasone 5 mg

Betamethasone Sodium Phosphate 2.63 mg, equivalent to betamethasone 2 mg

Excipients: disodium phosphate dihydrate 2.50 mg, sodium chloride 5.00 mg, disodium edetate 0.10 mg, polysorbate 80 0.50 mg, benzyl alcohol 9.00 mg, methyl parahydroxybenzoate 1.30 mg, propyl parahydroxybenzoate 0.20 mg, croscarmellose sodium 5.00 mg, macrogol (polyethylene glycol) 20.00 mg, hydrochloric acid solution 1.0 M q.s.. water for injection up to 1.00 ml

Special conditions

Cases of severe nervous system complications (up to fatal) have been reported with epidural and intrathecal administration of corticosteroids (with or without X-ray monitoring), including spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. The dosage regimen and the method of administration are set individually, depending on the indications, the severity of the disease and the patient's reaction. It is necessary to avoid intravascular ingestion of the drug.

The dose should be as small as possible, and the period of use as short as possible. The initial dose is selected until the desired therapeutic effect is achieved. Then gradually reduce the dose of the drug Flosterone ® to the minimum effective maintenance dose. In the absence of an effect from the therapy or with its long-term use, the drug Flosterone ® is also canceled, gradually reducing the dose, and another appropriate treatment method is selected.

After achieving a therapeutic effect, the maintenance dose is selected by gradually reducing the dose of betamethasone, administered at appropriate intervals. The dose reduction of the drug Flosterone ® is continued until the minimum effective dose is reached.

Withdrawal of the drug after prolonged therapy is carried out by gradually reducing the dose.

Monitoring of the patient's condition is carried out for at least a year after the end of long-term therapy or use in high doses.

The introduction of the drug into soft tissues, into the lesion or inside the joint can, with a pronounced local effect, simultaneously lead to a systemic effect.

Given the likelihood of developing anaphylactoid reactions with parenteral administration of corticosteroids, the necessary precautions should be taken before administration of the drug, especially if the patient has anamnestic indications of allergic reactions to drugs.

The drug Flosterone ® contains two active substances-derivatives of betamethasone, one of which-betamethasone sodium phosphate - quickly penetrates into the systemic circulation. When using the drug Flosterone ® , the possible systemic effect of the rapidly soluble fraction of the drug should be taken into account.

Against the background of the use of the drug Flosterone ® , mental disorders are possible (especially in patients with emotional instability or a tendency to psychosis).

The effect of corticosteroids increases in patients with cirrhosis of the liver or hypothyroidism.

When using the drug Flosterone ® in patients with diabetes mellitus, correction of hypoglycemic therapy may be required.

Patients receiving GCS should not be vaccinated against smallpox. Other immunizations should not be performed in patients receiving GCS therapy (especially in high doses), due to the possibility of developing neurological complications and a low immune response (lack of antibody formation). Flosterone ® should not be prescribed 8 weeks before and 2 weeks after vaccination with killed or inactivated viral and antibacterial vaccines. However, immunization is possible with replacement therapy (for example, with primary insufficiency of the adrenal cortex).

Patients using the drug Flosterone ® in doses that suppress the immune system should be warned about the need to avoid contact with patients with chickenpox and measles (especially important when using the drug in children).

When using the drug Flosterone ® , it should be borne in mind that GCS can mask the signs of an infectious disease, as well as reduce the body's resistance to infections.

It is necessary to carefully observe the rules of asepsis and antiseptics when administering the drug.

The use of the drug Flosterone ® in active tuberculosis is possible only in cases of rapid or disseminated tuberculosis in combination with adequate anti-tuberculosis therapy. When using the drug Flosterone ® in patients with latent tuberculosis or with a positive reaction to tuberculin, the question of preventive anti-tuberculosis therapy should be considered. When using rifampicin prophylactically, the acceleration of the hepatic clearance of betamethasone should be taken into account (dose adjustment may be required).

In the presence of fluid in the joint cavity, the septic process should be excluded. A noticeable increase in soreness, swelling, an increase in the temperature of the surrounding tissues and further restriction of joint mobility indicate infectious arthritis. It is necessary to conduct a study of the aspirated joint fluid in order to exclude infectious arthritis. If the diagnosis is confirmed - the use of the drug is contraindicated, it is necessary to prescribe antibacterial therapy.

Repeated injections into the joint in osteoarthritis can increase the risk of joint destruction. The introduction of GCS into the tendon tissue gradually leads to a rupture of the tendon. After successful intra-articular therapy, the patient should avoid overloading the joint.

Visual impairment can be registered during the use of systemic or local GCS. If the patient has symptoms such as blurred vision or other visual disturbances, then it should be decided to refer him to an ophthalmologist to assess possible causes, including cataracts, glaucoma, or rare diseases such as central serous chorioretinopathy (CSC), which have been reported after the use of systemic or topical corticosteroids.

Prolonged use of corticosteroids can lead to posterior subcapsular cataracts (especially in children), glaucoma with possible damage to the optic nerve, and may contribute to the development of secondary eye infection (fungal or viral). It is necessary to periodically conduct an ophthalmological examination, especially in patients using the drug Flosterone ® for more than 6 months.

With an increase in blood pressure, fluid retention and hypernatremia, and an increase in the excretion of potassium ions from the body (less likely than with other corticosteroids), patients are recommended a diet with a restriction of table salt and additionally prescribed potassium-containing drugs. All GCS increase the excretion of calcium ions (Ca+).

With the simultaneous use of the drug Flosterone ® and cardiac glycosides or drugs that affect the electrolyte composition of blood plasma, control of water-electrolyte metabolism is required.

With caution, acetylsalicylic acid is used simultaneously with the drug Flosterone ® in hypoprothrombinemia.

It is necessary to observe precautions when using the drug Flosterone ® in elderly patients and patients with a high risk of infection (who are on hemodialysis or with dentures), with renal or hepatic insufficiency, diverticulitis, osteoporosis.

The development of secondary adrenal cortex insufficiency associated with the rapid withdrawal of corticosteroid therapy is possible within a few months after the end of therapy. If a stressful situation occurs or threatens to occur during this period, therapy with Flosterone ® should be resumed and at the same time a mineralocorticosteroid drug should be prescribed (due to a possible violation of the secretion of mineralocorticosteroids). Gradual withdrawal of corticosteroid therapy can reduce the risk of secondary adrenal insufficiency.

It is possible to suppress the reaction during skin tests against the background of the use of GCS. Corticosteroids should be used with caution in patients with hypothyroidism or myasthenia gravis.

Special care should be taken when considering the possibility of systemic use of corticosteroids in patients with active herpetic eye damage (keratitis caused by the herpes simplex virus).

Cases of Kaposi's sarcoma have been reported in patients receiving corticosteroids, and discontinuation of this therapy may lead to remission of the disease.

Symptoms of peritoneal irritation or a reduction in pain due to perforation of the walls of the stomach or intestines may be minimal or absent in patients receiving GCS.

The immunosuppressive effect of GCS can lead to the activation of latent infection or exacerbation of intercurrent infections, including infections caused by microorganisms: Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia or Ameba. Special caution should be exercised when using corticosteroids in patients with a confirmed or suspected infection of Strongyloides (intestinal acne). In such patients, GCS-induced immunosuppression can lead to Strongyloides hyperinfection and spread of infection through larval migration, which is often accompanied by severe enterocolitis and septicemia caused by gram-negative microorganisms, possibly with a fatal outcome.

Since corticosteroids can exacerbate latent amoebiasis, all patients with unexplained diarrhea or patients arriving from countries with a tropical climate should be examined to exclude amoebiasis before starting corticosteroid therapy.

In the event of a stressful situation (not related to the disease), it may be necessary to increase the dose of the drug Flosterone ® , the drugs of choice as a supplement should be hydrocortisone and cortisone.

With long-term therapy of corticosteroids, it is advisable to consider the possibility of switching from parenteral corticosteroids to oral corticosteroids, taking into account the assessment of the "benefit/risk" ratio.

Use in pediatrics

Children who are undergoing therapy with Flosterone ® (especially long-term) should be carefully monitored for possible growth retardation and the development of adrenal cortex insufficiency.

Fertility

Against the background of the use of GCS, it is possible to change the motility and number of spermatozoa.

Use in athletes

Betamethasone may affect the results of doping control.

Influence on the ability to drive vehicles, mechanisms

During the treatment period, it is necessary to refrain from driving vehicles, mechanisms and engaging in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Drug interaction

With the simultaneous use of phenobarbital, rifampicin, phenytoin, aminoglutetimide or ephedrine, it is possible to accelerate the metabolism of the drug while reducing its therapeutic activity.

With the simultaneous use of corticosteroids and estrogens, a dose adjustment of betamethasone may be required (due to the risk of overdose).

With the simultaneous use of betamethasone and potassium-withdrawing diuretics, the likelihood of hypokalemia increases.

Concomitant use of corticosteroids and cardiac glycosides increases the risk of arrhythmia or digitalis intoxication (due to hypokalemia).

Betamethasone may enhance the excretion of potassium ions (K+) caused by amphotericin B.

With the simultaneous use of betamethasone and indirect anticoagulants, changes in blood clotting may occur, requiring dose adjustment of anticoagulants.

With the combined use of GCS with nonsteroidal anti-inflammatory drugs (NSAIDs) or with ethanol and ethanol-containing drugs, it is possible to increase the frequency or intensity of erosive and ulcerative lesions of the gastrointestinal tract.

Corticosteroids can reduce the concentration of salicylates in the blood plasma.

Simultaneous administration of corticosteroids and somatropin may lead to a slowdown in the absorption of the latter (doses of betamethasone exceeding 0.3-0.45 mg/m2 of body surface area per day should be avoided).

GCS can affect the nitrogen blue tetrazole test for bacterial infection and cause a false negative result.

When using betamethasone, patients with diabetes may need to adjust hypoglycemic therapy.

Corticosteroids may reduce the effects of cholinesterase inhibitors.

With simultaneous use with corticosteroids, there was a decrease in the concentration of isoniazid in the blood plasma. The condition of patients taking isoniazid should be carefully monitored.

The simultaneous use of cyclosporine and corticosteroids may lead to an increase in the concentration of cyclosporine and an increase in the action of corticosteroids. There is a high risk of seizures.

Concomitant use of certain corticosteroids with inhibitors of the CYP3A4 isoenzyme (for example, macrolide antibiotics, ketoconazole) may reduce the elimination of corticosteroids.

Concomitant use of inhibitors of the CYP3A isoenzyme, including cobicistat-containing drugs, may lead to an increased risk of systemic adverse reactions (HP). Simultaneous use should be avoided, except in situations where the expected benefit of using such a combination exceeds the risk of developing systemic HP. In such cases, patients should be informed about systemic HP and be under close medical supervision.

With simultaneous use with colestyramine, it is possible to increase the excretion of corticosteroids.

Pharmacodynamics

Betamethasone is a synthetic corticosteroid that has high glucocorticoid and low mineralocorticoid activity. Inhibits the release of interleukin-1, interleukin-2, and gamma-interferon from lymphocytes and macrophages. It has anti-inflammatory, anti-allergic, desensitizing, anti-shock, antitoxic and immunosuppressive effects. It suppresses the release of adrenocorticotropic hormone (ACTH) and beta-lipotropin by the pituitary gland, but does not reduce the concentration of beta-endorphin circulating in the blood plasma. It inhibits the secretion of thyroid-stimulating hormone (TSH) and follicle-stimulating hormone (FSH).

Increases the excitability of the central nervous system( CNS), reduces the number of lymphocytes and eosinophils. Increases the number of red blood cells (by increasing the production of erythropoietins).

It interacts with specific cytoplasmic receptors and forms a complex that penetrates into the cell nucleus, and stimulates the synthesis of matrix ribonucleic acid( RNA), the latter induces the formation of proteins, including lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid, and inhibits the synthesis of endoperoxides, prostaglandins( Pg), and leukotrienes, which contribute to the processes of inflammation, allergies, and others.

Effect on protein metabolism: reduces the amount of protein in the blood plasma (due to globulins) with an increase in the albumin/globulin ratio, increases the synthesis of albumins in the liver and kidneys, increases protein catabolism in muscle tissue.

Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Effect on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract (GIT), increases the activity of glucose-6-phosphatase, which leads to an increase in the intake of glucose from the liver into the blood, increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, which lead to the activation of gluconeogenesis.

Effect on water-electrolyte metabolism: delays sodium ions (Na+) and water in the body, stimulates the excretion of potassium ions (K+) (mineralocorticosteroid activity), reduces the absorption of calcium ions (Ca2+) from the gastrointestinal tract, "washes" calcium ions (Ca2+) from the bones and increases their excretion by the kidneys.

The anti-inflammatory effect is due to the inhibition of the release of inflammatory mediators by eosinophils; inducing the formation of lipocortin and reducing the number of mast cells that produce hyaluronic acid; reducing the permeability of capillaries; stabilizing cell membranes and organelle membranes (especially lysosomal).

The anti-allergic effect is associated with the suppression of the synthesis and secretion of allergy mediators, inhibition of the release of histamine from sensitized mast cells and basophils, etc. biologically active substances, T-and B-lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, changing the immune response of the body. In chronic obstructive pulmonary disease (COPD), the action is mainly based on inhibition of inflammatory processes, inhibition of the development or prevention of edema 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 on inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of small and medium-sized bronchial beta-adrenoreceptors 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 (BP) (due to an increase in the concentration of catecholamines circulating in the blood plasma and the restoration of the sensitivity of adrenoreceptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane - protective properties, activation of liver enzymes involved in the metabolism of endo-and xenobiotics.

The immunosuppressive effect is caused by inhibition of the release of cytokines (interleukin-1, interleukin-2, gamma-interferon) from lymphocytes and macrophages. It suppresses the synthesis and secretion of ACTH and, secondarily, the synthesis of endogenous corticosteroids. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Betamethasone sodium phosphate is an easily soluble compound that is well absorbed after parenteral administration into the tissues and provides a quick effect. Betamethasone dipropionate has a slower absorption. By combining these salts, it is possible to create a drug with both short-term (but fast) and long-term action. Depending on the method of use (intravenous (IV), intramuscular (iv), intraarticular, periarticular, intradermal (IV)) a general or local effect is achieved.

Pharmacokinetics

Betamethasone sodium phosphate is highly soluble in water, and after intravenous administration is rapidly hydrolyzed and almost immediately absorbed from the injection site, which provides a rapid onset of therapeutic action. It is almost completely eliminated within one day after administration. Betamethasone dipropionate is slowly absorbed from the depot, metabolized gradually, which causes a long-term effect of the drug, and is excreted for more than 10 days.

Betamethasone binds well to plasma proteins (62.5 %). It is metabolized in the liver with the formation of mainly inactive metabolites. It is mainly excreted by the kidneys.

Indications

Treatment in adult patients of conditions and diseases in which GCS therapy allows to achieve the necessary clinical effect (it should be taken into account that in some diseases of GCS therapy is additional and does not replace standard therapy):

• diseases of the musculoskeletal system and soft tissues, including rheumatoid arthritis, osteoarthritis, bursitis, ankylosing spondylitis, epicondylitis, coccygodynia, torticollis, ganglion cyst, fasciitis;
• allergic diseases, including bronchial asthma, hay fever( hay fever), allergic bronchitis, seasonal or year-round rhinitis, drug allergy, serum sickness, reactions to insect bites;
• dermatological diseases, including atopic dermatitis, monetoid eczema, neurodermatitis, contact dermatitis, severe photodermatitis, urticaria, lichen planus, nest alopecia, discoid lupus erythematosus, psoriasis, keloid scars, common pemphigus, cystic acne;
• systemic connective tissue diseases, including systemic lupus erythematosus, scleroderma, dermatomyositis, and nodular periarteritis;
• hemoblastosis (palliative therapy of leukemia and lymphoma in adult patients, acute leukemia in children);
• primary or secondary insufficiency of the adrenal cortex (with mandatory simultaneous use of mineralocorticosteroids);
• other diseases and pathological conditions that require systemic corticosteroid therapy (adrenogenital syndrome, regional ileitis, pathological changes in the blood if corticosteroid therapy is necessary).

Contraindications

• Hypersensitivity to betamethasone, any of the excipients of the drug, or other corticosteroids.
• Systemic mycoses.
• Intravenous or subcutaneous administration.
• Intra-articular injection: unstable joint, infectious arthritis.
• Injection into infected cavities and into the intervertebral space.
• Epidural, intrathecal administration and administration of the drug directly into the muscle tendons.
• Coagulation disorders (including treatment with anticoagulants).
• Simultaneous administration of immunosuppressive doses of the drug with live or weakened vaccines.
• Edema of the brain due to traumatic brain injury.
• The period of breastfeeding.
• Children under 3 years of age (the presence of benzyl alcohol in the composition).

With caution

• Parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transmitted, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chickenpox, measles, amoebiasis, strongyloidosis (established or suspected), active or latent tuberculosis. Use in severe infectious diseases is allowed only against the background of specific antimicrobial therapy.
• Post-vaccination period (a period of 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.
• Immunodeficiency conditions (including acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection).
• Gastrointestinal diseases: gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscission, diverticulitis, abscess or other purulent infections.
• Diseases of the cardiovascular system, including recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the focus of necrosis, slowing the formation of scar tissue and, consequently, rupture of the heart muscle), decompensated chronic heart failure (CHF), arterial hypertension, hyperlipidemia.
• Endocrine diseases - diabetes mellitus (including reduced glucose tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Cushing's disease.
• Severe chronic renal and / or hepatic insufficiency, nephrourolithiasis, cirrhosis of the liver.
• Thrombocytopenic purpura (IV administration).
• Hypoalbuminemia and conditions predisposing to its occurrence.
• Systemic osteoporosis, myasthenia gravis, acute psychosis, obesity (grade III-IV), polio (except for the form of bulbar encephalitis), open-and closed-angle glaucoma, eye diseases caused by Herpes simplex (due to the risk of corneal perforation), pregnancy.
• For intra-articular administration: the general serious condition of the patient, the ineffectiveness (or short duration) of the action of the 2 previous injections (taking into account the individual properties of the used GCS).
• Use in elderly patients due to hypersensitivity to corticosteroids, especially in postmenopausal women (high risk of osteoporosis).
• With convulsive syndrome.

Use during pregnancy and during breastfeeding

Pregnancy

Due to the lack of controlled studies on the safety of the use of betamethasone during pregnancy, the use of the drug Flosterone ® during pregnancy or in women with preserved reproductive potential is indicated only if the expected therapeutic effect for the mother exceeds the risk of possible negative effects of the drug on the fetus. Newborns whose mothers received therapeutic doses of corticosteroids during pregnancy should be under medical supervision (for early detection of signs of adrenal insufficiency). GCS penetrate the placental barrier and can reach high concentrations in the fetus.

The use of corticosteroids in pregnant animals can cause fetal malformations, including cleft palate ("cleft palate"), delayed fetal development, and affect the growth and development of the brain. There is no evidence of an increase in the number of cases of congenital malformations, such as cleft palate/lip, in humans due to the use of corticosteroids. However, with prolonged or repeated use during pregnancy, the use of corticosteroids may increase the risk of delayed fetal development. Theoretically, after prenatal use of corticosteroids, it is possible to develop adrenal hypofunction in newborns, which, as a rule, spontaneously passes after birth and in rare cases is clinically significant. Cases of myocardial hypertrophy and gastroesophageal reflux have been reported in newborns when using betamethasone during pregnancy.

The condition of patients with fluid retention or gestosis of the second half of pregnancy (especially severe - preeclampsia, eclampsia) should be carefully monitored.

With systemic use in pregnant women, betamethasone can lead to a transient decrease in heart rate (HR) and inhibition of fetal biophysical activity, which are widely used to assess the condition of the fetus. These characteristics may include a decrease in the number of respiratory movements, fetal motor activity, and fetal heart rate.

Breastfeeding period

If it is necessary to use the drug Flosterone ® during breastfeeding, given the importance of corticosteroid therapy for the mother and the likelihood of developing adverse reactions in the child, breastfeeding should be discontinued.

Overdose

Symptoms

Acute overdose of betamethasone does not lead to life-threatening situations. The introduction of high doses of GCS for several days does not lead to undesirable consequences (except in cases of very high doses or when used in diabetes mellitus, glaucoma, exacerbation of erosive and ulcerative lesions of the gastrointestinal tract or with the simultaneous use of cardiac glycosides, indirect anticoagulants or potassium-withdrawing diuretics).

Treatment

Careful medical monitoring of the patient's condition is necessary, optimal fluid intake should be maintained, and the content of electrolytes in the blood plasma and in the urine (especially the ratio of sodium ions (Na+) and potassium ions (K+)) should be monitored. If necessary, appropriate therapy should be performed.

Side effects

The frequency of development and severity of side effects, as with the use of other corticosteroids, depend on the dose and duration of use of the drug. These phenomena are usually reversible and can be eliminated or reduced by reducing the dose.

Disorders of the immune system: anaphylactic reactions, anaphylactic shock, angioedema.

Disorders of the endocrine system: suppression of the function of the adrenal glands and pituitary gland, secondary adrenal insufficiency (especially during stress during illness, trauma, surgery), Itsenko-Cushing syndrome, decreased glucose tolerance, "steroid" diabetes mellitus or the manifestation of latent diabetes mellitus, increased need for insulin or oral hypoglycemic drugs, growth and sexual development delay in children, hirsutism, hypertrichosis, when using betamethasone during pregnancy, is a delay in intrauterine development of the fetus.

Metabolic and nutritional disorders: negative nitrogen balance (due to protein catabolism), lipomatosis (including mediastinal and epidural lipomatosis, which can cause neurological complications), weight gain, increased appetite, hypernatremia, increased excretion of potassium ions (K+), increased excretion of calcium ions (Ca2+), hypokalemic alkalosis, fluid retention in tissues.

Mental disorders: euphoria, mood changes, depression (with pronounced psychotic reactions), personality disorders, increased irritability, insomnia.

Disorders of the nervous system: convulsions, increased intracranial pressure with edema of the optic disc (more often at the end of therapy), dizziness, headache, neuritis, neuropathy, paresthesia, with intrathecal administration-arachnoiditis, meningitis, paresis/paralysis, sensory disorders.

Visual organ disorders: posterior subcapsular cataract, increased intraocular pressure, glaucoma, exophthalmos, in rare cases - blindness (when the drug is administered to the face and head), blurred vision (see also the section "Special instructions").

Cardiac disorders: CHF (in predisposed patients), cardiac arrhythmias, bradycardia, tachycardia, hypertrophic myopathy in premature infants, myocardial rupture after a recent myocardial infarction.

Vascular disorders: increased blood pressure, thromboembolic complications, vasculitis, decreased blood pressure.

Disorders of the gastrointestinal tract: erosive and ulcerative lesions of the gastrointestinal tract with possible subsequent perforation and bleeding, flatulence, hiccups, nausea.

Disorders of the liver and biliary tract: pancreatitis, hepatomegaly, increased activity of "liver" enzymes (usually reversible).

Disorders of the skin and subcutaneous tissues: impaired wound healing, atrophy and thinning of the skin, petechiae, ecchymosis, increased sweating, dermatitis, "steroid" acne, striae, a tendency to develop pyoderma and candidiasis, decreased reaction during skin tests, urticaria, skin rash, thinning of the hair on the head, allergic dermatitis, erythema.

Musculoskeletal and connective tissue disorders: muscle weakness, "steroid" myopathy, loss of muscle mass, increased myasthenic symptoms in severe pseudoparalytic myasthenia gravis, osteoporosis, compression fracture of the spine, aseptic necrosis of the femoral or humerus head, pathological fractures of the tubular bones, tendon ruptures, joint instability (with repeated intra-articular injections).

Disorders of the genitals and breast: violation of the menstrual cycle, changes in the mobility and number of spermatozoa.

General disorders and disorders at the injection site: (associated with parenteral administration of the drug): rarely-hyper-or hypopigmentation, subcutaneous and cutaneous atrophy, aseptic abscesses, a rush of blood to the skin of the face after injection (or intra-articular injection), neurogenic arthropathy.