Prednisone

Pharmacological properties

It has anti-inflammatory, anti-allergic, immunosuppressive, anti-shock and anti-toxic effects. at relatively high doses, it inhibits the activity of fibroblasts, the synthesis of collagen, reticuloendothelium and connective tissue (inhibition of the proliferative phase of inflammation) delays the synthesis and accelerates protein catabolism in muscle tissue, but increases its synthesis in the liver. antiallergic and immunosuppressive properties of the drug are due to inhibition of the development of lymphoid tissue with its involution with prolonged use, a decrease in the number of circulating T and b lymphocytes, inhibition of mast cell degranulation, and inhibition of antibody production.

The antishock effect of the drug is due to an increase in the response of blood vessels to endogenous and exogenous vasoconstrictors, with a restoration of the sensitivity of vascular receptors to catecholamines and an increase in their hypertensive effect, as well as a delay in the excretion of sodium and water from the body.

The antitoxic effect of the drug is associated with stimulation of protein synthesis in the liver and accelerated inactivation of endogenous toxic metabolites and xenobiotics in it, as well as with increased stability of cell membranes, including hepatocytes.

It enhances the deposition of glycogen and the synthesis of glucose from protein metabolism products in the liver. An increase in blood glucose activates the release of insulin. Suppresses the uptake of glucose by fat cells, which leads to the activation of lipolysis. However, due to increased insulin secretion, lipogenesis is stimulated, which contributes to the accumulation of fat. Reduces the absorption of calcium in the intestine, increases its leaching from bones and excretion by the kidneys. It inhibits the release of ACTH and β-lipotropin by the pituitary gland, and therefore, with prolonged use, the drug can contribute to the development of functional insufficiency of the adrenal cortex.

The main factors limiting the long-term therapy with prednisone are osteoporosis and Itsenko-Cushings syndrome. Prednisolone inhibits the secretion of thyroid-stimulating and follicle-stimulating hormones.

In high doses, it can increase the excitability of brain tissue and help lower the threshold for convulsive readiness.

Stimulates the excessive secretion of hydrochloric acid and pepsin in the stomach, and therefore can cause the development of peptic ulcers.

Pharmacokinetics When introduced, it is absorbed into the blood quickly, but compared with reaching the maximum level in the blood, the pharmacological effect of the drug is significantly delayed and develops for 2-8 hours. In the blood plasma, most of prednisolone binds to transcortin (a cortisol-binding globulin), and when the process is saturated, to albumin. With a decrease in protein synthesis, a decrease in the binding ability of albumin is observed, which can lead to an increase in the free fraction of prednisolone and, as a result, to the manifestation of its toxic effect when using conventional therapeutic doses. T_½ in adults - 2–4 hours, in children - shorter. It is metabolized by oxidation mainly in the liver, as well as in the kidneys, small intestine, bronchi. The oxidized forms are glucuronidized or sulfated and excreted in the form of conjugates by the kidneys.

About 20% of prednisolone is excreted from the body by the kidneys unchanged, a small part - with bile.

In liver diseases, prednisolone metabolism slows down and its degree of binding to blood plasma proteins decreases, which leads to an increase in T_½ the drug.

Indications

V / m, iv introduction:

• systemic diseases of the connective tissue: systemic lupus erythematosus, dermatomyositis, scleroderma, periarthritis nodosa, ankylosing spondylitis;
• hematological diseases: acute hemolytic anemia, lymphogranulomatosis, granulocytopenia, thrombocytopenic purpura, agranulocytosis, various forms of leukemia;
• skin diseases: common eczema, erythema multiforme exudative, pemphigus vulgaris, erythroderma, exfoliative dermatitis, seborrheic dermatitis, psoriasis, alopecia, adrenogenital syndrome;
• replacement therapy: Addisons crisis;
• emergency conditions: severe forms of ulcerative colitis and Crohn’s disease, shock (burn, traumatic, surgical, anaphylactic, toxic, transfusion), asthmatic status, acute adrenal cortex insufficiency, hepatic coma, severe allergic and anaphylactic reactions, hypoglycemic conditions.

Intra-articular administration: chronic polyarthritis, osteoarthritis of large joints, rheumatoid arthritis, post-traumatic arthritis, arthrosis.

Application

Mixing and simultaneous use of prednisolone with other drugs in the same infusion system or syringe is not allowed!

The drug is intended for intravenous, intramuscular or intraarticular administration. The dose of prednisone depends on the severity of the disease.

For the treatment of adults, the daily dose is 4-60 mg IV or IM.

In children, the drug should be prescribed IM (deep into the gluteus maximus) strictly according to the indications and under the supervision of a doctor: for children aged 6–12 years, 25 mg / day, for older than 12 years, 25–50 mg / day. The duration of use and the number of injections of the drug are determined individually.

In Addisons disease, the daily dose for adults is 4–60 mg IV or IM.

In severe ulcerative colitis, 8–12 ml / day (240–360 mg of prednisolone) for 5–6 days; in severe Crohn’s disease, 10–13 ml / day (300–390 mg of prednisolone) for 5-7 days.

In emergency conditions, prednisone is administered intravenously slowly (for about 3 minutes) or drip at a dose of 30-60 mg. If the IV infusion is difficult, the drug is administered IM, deeply. With this method of administration, the effect develops more slowly. If necessary, the drug is reintroduced in / in or / m at a dose of 30-60 mg after 20-30 minutes.

In some cases, an increase in the specified dose is allowed, this is decided by the doctor individually in each case.

For adults, the dose of prednisone with intra-articular administration is 30 mg for large joints, 10–25 mg for medium-sized joints and 5–10 mg for small joints. The drug is administered every 3 days. The course of treatment is up to 3 weeks.

Contraindications

Hypersensitivity to the drug.

Parasitic and infectious diseases of viral, fungal or bacterial etiology that exist now or have recently been transferred: herpes simplex, herpes zoster (viraemic phase), chickenpox, measles; amoebiasis, strongyloidosis (established or suspected); systemic mycosis, active or latent tuberculosis.

Post-vaccination period (duration - 10 or 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.

Immunodeficiency conditions caused by HIV infection.

Digestive tract diseases: gastric and duodenal ulcers, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastamosis, ulcerative colitis with the threat of perforation or abscess, diverticulitis.

Diseases of the cardiovascular system: recent myocardial infarction, decompensated chronic heart failure, hypertension, tendency to thromboembolic disease.

Diseases of the endocrine system: diabetes mellitus and impaired carbohydrate tolerance, thyrotoxicosis, hypothyroidism, Itsenko-Cushings disease.

Severe chronic renal and / or liver failure, nephrourolithiasis.

Hypoalbuminemia. Systemic osteoporosis. Myasthenia gravis. Acute psychosis. Severe myopathy Productive symptoms in mental illness, psychosis. Obesity (III – IV degree). Polio (except for the form of bulbar encephalitis).Open and closed angle glaucoma, cataract.

For intraarticular injections - infections in the area of ​​administration.

Side effects

The development of severe adverse reactions depends on the dose and duration of treatment. adverse reactions usually develop with prolonged treatment with the drug, for a short period the risk of their occurrence is unlikely.

Infections and infestations: masking the symptoms of bacterial, viral, fungal infections, opportunistic infections.

Blood system and lymphatic system: an increase in the total number of white blood cells with a decrease in the number of eosinophils, monocytes and lymphocytes. The mass of lymphoid tissue is reduced. Blood coagulation, hypercoagulation may increase, leading to thrombosis, thromboembolism.

Endocrine system and metabolism: decreased glucose tolerance, steroid diabetes mellitus or the manifestation of latent diabetes mellitus, increased need for insulin and oral hypoglycemic drugs, hyperlipidemia, inhibition of the hypothalamic-pituitary-adrenal system, growth retardation in children and adolescents, delayed growth , menstrual irregularities, impaired production of sex hormones (amenorrhea), postmenopausal bleeding, Itsenko-Cushings syndrome (moon-shaped face, fat of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae).

From the side of metabolism: a negative balance of nitrogen and calcium, a violation of the mineral and electrolyte balance, hypokalemic alkalosis. Side effects due to the corticosteroids activity of prednisone: fluid retention and Na⁺ (peripheral edema), hypernatremia, hypokalemic syndrome - arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue.

Mental disorders: irritability, delirium, disorientation, euphoria, hallucinations, depression, paranoia, nervousness, anxiety, anxiety, sleep disturbances, insomnia, euphobia, suicidal tendency, labile mood, increased concentration, psychological dependence, mania, manic-depressive psychosis, exacerbation of schizophrenia, dementia, psychosis, epileptic seizures, cognitive dysfunction (including amnesia and impaired consciousness).

Nervous system: peripheral neuropathy, paresthesia, dizziness, headache, autonomic disorders, increased intracranial pressure, accompanied by vomiting, cerebellar pseudotumor, seizures.

Organ of vision: increased intraocular pressure with possible damage to the optic nerve, glaucoma, swelling of the optic disc, cataracts, thinning of the cornea and sclera, trophic changes in the cornea, exacerbation of viral and fungal infections, exophthalmos.

Cardiovascular system: arterial hypo- or hypertension, bradycardia, arrhythmia, asystole (due to the rapid administration of the drug), the development or increase in the manifestations of chronic heart failure, atherosclerosis, thrombosis, vasculitis, peripheral edema, ECG changes characteristic of hypokalemia. In patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing the formation of the scar, which can lead to rupture of the heart muscle.

On the part of the immune system: hypersensitivity reactions, including rash, skin itching, urticaria, hyperemia, Quinckes edema, anaphylactic shock.

Digestive system: nausea, vomiting, flatulence, an unpleasant aftertaste in the mouth, dyspepsia, increased or decreased appetite, hiccups, epigastric pain, diarrhea, erosive esophagitis, peptic ulcers with perforation and bleeding, esophageal ulcer, esophageal candidiasis, pancreatic pancreatitis, perforation , gastric bleeding, local ileitis and ulcerative colitis.During the period of use of the drug, there may be an increase in AlAT, AsAT and alkaline phosphatase, which is usually not important and reversible after discontinuation of the drug.

On the part of the skin and subcutaneous tissue: slowing down the regeneration process, petechiae, bruising, hematoma, ecchymosis, striae, thinning of the skin, hyper- or hypopigmentation, acne, tendency to develop pyoderma, skin atrophy, telangiectasia, acne, hirsutism, purpura, poststeroid panniculitis, characterized by the appearance of erythematosis, hot subcutaneous thickening within 2 weeks after discontinuation of the drug, Kaposis sarcoma.

Musculoskeletal system: growth retardation and ossification processes in children (premature closure of the epiphyseal growth zones), proximal myopathy, osteoporosis, rupture of tendons of muscles, muscle weakness, decrease in muscle mass (atrophy), steroid myopathy, fractures of the spine and long bones, aseptic osterosis , very rarely, pathological bone fractures.

Urinary system: increased risk of urate, uralitis, an increase in the number of leukocytes and red blood cells in the urine without damage to the kidneys, leukocyturia.

General: malaise, persistent hiccups when using the drug in high doses, adrenal insufficiency, which leads to arterial hypotension, hypoglycemia and fatal cases in stressful situations, such as surgery, trauma or infection, if the dose of prednisone is not increased.

With sudden drug withdrawal, withdrawal syndrome is possible, the severity of the symptoms of which depends on the degree of adrenal atrophy, headache, nausea, abdominal pain, dizziness, anorexia, weakness, mood changes, lethargy, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itching skin weight loss. In more severe cases - severe mental disorders and increased intracranial pressure, steroid pseudo-rheumatism in patients with rheumatism, fatal cases.

Reactions at the injection site: pain, burning, changes in pigmentation (depigmentation, leukoderma), skin atrophy, sterile abscesses, rarely lipoatrophy.

special instructions

In infectious diseases (which are not indicated in the contraindications section) and latent forms of tuberculosis, the drug should be prescribed only in combination with antibiotics and anti-tuberculosis drugs.

In case of violation of tolerance to carbohydrates, the drug should be used with caution.

If it is necessary to use prednisone while taking oral hypoglycemic drugs or anticoagulants, it is necessary to correct the dosage regimen of the latter.

In patients with thrombocytopenic purpura, the drug is used only iv.

A clinical examination should include a study of the cardiovascular system, X-ray examination of the lungs, a study of the stomach and duodenum, urinary system, and organ of vision. Laboratory examination should include: a general blood test, the concentration of glucose in the blood and urine, electrolytes in blood plasma.

When using GCS for a long time, it is recommended to regularly monitor blood pressure, determine the level of glucose in urine and blood, analyze feces for occult blood, analyze blood coagulation parameters, X-ray control of the spine, eye examination (1 time in 3 months).

Treatment even at low doses masks the signs and symptoms of preexisting infections that developed during treatment (including opportunistic infections) and makes their diagnosis difficult. During treatment, contact with sick colds or other infections should be avoided.

For children who were in contact with measles or chickenpox during treatment, specific immunoglobulins should be prescribed as prophylaxis (within 10 days after contact).

During treatment should not be immunized.

If during the treatment of corticosteroids, patients experience unusual stressful situations, it is recommended to increase the dose of fast-acting corticosteroids before, during and after a stressful situation.

During treatment with prednisone, you should not drink alcohol.

Depending on the duration of treatment and dose, a negative effect of the drug on calcium metabolism is possible. The prevention of osteoporosis is recommended, which is especially important if patients have risk factors (including family predisposition, old age, postmenopause, insufficient intake of protein and calcium, excessive smoking, excessive alcohol consumption, and a decrease in physical activity). Prevention is based on the adequate intake of calcium and vitamin D, and also includes physical activity.

To reduce the severity of side effects of prednisone therapy, the appointment of an appropriate diet is justified.

When using prednisone in high doses for a long period (30 mg / day for at least 4 weeks), reversible spermatogenesis disorders can occur that persist for several months after stopping the drug.

In patients who received prednisone at a dose higher than physiological (approximately 7.5 mg of prednisolone or equivalent), more than 3 weeks, treatment with prednisolone should be discontinued gradually. Therapy should be discontinued gradually, even if it lasted less than 3 weeks, for the following groups of patients:

• undergoing a second course of treatment with prednisone;
• by whom a repeated course of treatment was prescribed within a year after long-term treatment (months, years);
• receiving 40 mg / day of prednisone or equivalent;
• with adrenal insufficiency, the cause of which is not exogenous administration of corticosteroids.

After discontinuation of treatment, withdrawal syndrome, adrenal insufficiency, as well as an exacerbation of the disease, due to which prednisolone was prescribed, may occur. If after the end of treatment with prednisone functional adrenal insufficiency is observed, the use of the drug should be resumed immediately, and the dose reduction should be carried out very slowly and with caution (for example, the daily dose should be reduced by 2-3 mg for 7-10 days).

Atrophy of the adrenal cortex develops with prolonged therapy and can persist for many years after discontinuation of treatment.

Steroid-induced secondary adrenal insufficiency can be minimized due to a gradual dose reduction. This type of insufficiency can persist for several months after the end of therapy, therefore, for any stressful situation that arose during this period, it is necessary to resume therapy with corticosteroids.

With a sudden withdrawal of the drug, especially in the case of previous use in high doses, withdrawal syndrome occurs, which is manifested by fever, decreased appetite, nausea, vomiting, diarrhea, lethargy, dizziness, generalized musculoskeletal pain, asthenia.

Because of the danger of developing hypercorticism, a new course of treatment with cortisone after previous long-term treatment with prednisolone for several months should always be started with low initial doses (with the exception of the use for health reasons). With caution, it is prescribed after a recent myocardial infarction (in patients with acute, subacute myocardial infarction, the spread of the necrosis focus, slowing down the formation of scar tissue, and rupture of the heart muscle).

With a history of psoriasis, prednisone in high doses is used with extreme caution.

If there is a history of seizures, prednisone should be used only at the minimum effective dose.

With extreme caution, the drug should be used for migraines, the presence of a history of data on some parasitic diseases (especially with amoebiasis).

With extreme caution prescribed for immunodeficiency conditions (including AIDS or HIV infection).

In children, during the period of GCS growth, it can be used only according to absolute indications and under especially careful medical supervision.

With intercurrent infections, septic conditions, it is necessary to simultaneously conduct antibiotic therapy.

The electrolyte balance should be carefully monitored with the combined use of prednisone with diuretics. With prolonged treatment with prednisone, in order to prevent hypokalemia, potassium preparations and an appropriate diet should be prescribed in connection with a possible increase in intraocular pressure and the development of subcapsular cataract.

Use in severe infectious diseases (not indicated in the “CONTRAINDICATIONS” section) is possible only against the background of specific antimicrobial therapy.

Menopausal women need to undergo studies regarding the possible occurrence of osteoporosis.

In Addisons disease, the simultaneous use of barbiturates should be avoided due to the risk of acute adrenal insufficiency (Addisons crisis).

With extreme caution, the drug should be used for hepatic and renal failure.

Particular attention is required to use systemic corticosteroids in patients with existing or history of severe affective disorders, including depressive, manic-depressive psychosis, previous steroid psychosis. Patients and / or guardians should be warned of the possibility of serious side effects from the psyche. Symptoms usually appear within a few days or weeks after starting treatment. The risk of these side effects is higher when used in high doses. Most reactions disappear after a dose reduction or drug withdrawal, although specific treatment is sometimes necessary. With the development of such symptoms, you should consult a doctor. Mental disorders are also possible during the withdrawal of glucocorticoids.

Use during pregnancy and lactation. During pregnancy, the drug can not be used. If it is necessary to use the drug, breast-feeding should be discontinued.

Children. Use in children over 6 years of age exclusively for the intended purpose and under the supervision of a physician. The doctor determines the doses and duration of therapy individually, depending on the age and severity of the course of the disease. With prolonged use in children, growth retardation is possible, therefore it is necessary to limit the use of minimum doses for certain indications for a short period. The benefits of treatment should exceed the possible risk of side effects.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Patients who are treated with prednisone should refrain from potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Interactions

With the simultaneous use of prednisolone with other drugs, it is possible:

• with thyroid hormones, inducers of liver enzymes, in particular with barbiturates, phenytoin, pyrimidone, carbamazepine, rifampicin: weakening effects of prednisolone due to an increase in its systemic clearance;
• with estrogens (including oral contraceptives, which include estrogen), cyclosporine, CYP 3A4 inhibitors, in particular erythromycin, clarithromycin, ketoconazole, diltiazem, aprepitant, itraconazole, oleandomycin: increased therapeutic and toxic effects of prednisolone;
• with antacids: decreased absorption of prednisolone;
• with derivatives of salicylic acid and other NSAIDs: increased likelihood of ulceration of the gastric mucosa; prednisone reduces the level of salicylic acid derivatives in the blood serum, increasing their renal clearance; the drug increases the risk of hepatotoxic reactions of paracetamol due to the induction of liver enzymes and the formation of its toxic metabolite;
• with cardiac glycosides: increased toxicity of the latter, and as a result of hypokalemia, an increased risk of arrhythmias;
• with hypoglycemic agents: suppression of the hypoglycemic effect of oral hypoglycemic agents and insulin;
• with antihypertensive drugs: decreased effectiveness of the latter;
• with tricyclic antidepressants: increased signs of depression caused by the use of prednisone and increased intraocular pressure;
• with immunosuppressants: increased risk of infections and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus;
• with diuretics, laxatives, amphotericin B: increased risk of hypokalemia; prednisone increases the risk of developing osteoporosis while using amphotericin and carbonic anhydrase inhibitors;
• with M-anticholinergics, antihistamines, nitrates: increased intraocular pressure and decreased effectiveness of antihistamines;
• with antipsychotics, carbamide, azathioprine: increased risk of cataracts;
• with estrogens, anabolic drugs, oral contraceptives: manifestations of hirsutism and acne;
• with live antiviral vaccines and against the background of other types of immunization: increased risk of virus activation and the development of infections;
• with muscle relaxants against the background of hypokalemia: an increase in the severity and duration of muscle blockade with the use of muscle relaxants;
• with anticholinesterase agents: the occurrence of muscle weakness in patients with myasthenia gravis (especially in patients with gravis myasthenia gravis);
• with mitotan and other inhibitors of adrenal cortex function: may cause an increase in the dose of the drug;
• with antiemetic agents: increased antiemetic effect;
• with isoniazid, mexiletine, praziquantel: a decrease in their plasma concentrations;
• with somatropin (in high doses): a decrease in the effect of the latter;
• with fluoroquinolones: tendon damage;
• with cyclosporine: there have been cases of seizures. Since the simultaneous administration of these drugs causes a mutual inhibition of metabolism, it is likely that convulsions and other side effects associated with the use of each of these drugs as monotherapy can occur more often with their combined use. The combined use can cause an increase in the concentration of other drugs in the blood plasma.

With prolonged therapy, prednisone increases the content of folic acid.

The drug reduces the effect of vitamin D on Ca absorption²⁺ in the intestinal cavity.

Incompatibility. Prednisone cannot be mixed and used simultaneously with other drugs in the same infusion system or in the same syringe.

When mixing the solution of prednisone with heparin, a precipitate forms.

Incompatible with aerosols of sympathomimetic agents for treating AD in children (risk of respiratory paralysis).

Overdose

In case of an overdose, nausea, vomiting, bradycardia, arrhythmia, increased symptoms of heart failure, cardiac arrest, hypokalemia, increased hell, convulsions, hyperglycemia, thromboembolism, acute psychosis, dizziness, headache, symptoms of hypercorticism may develop: increased body weight, development of edema , ag, glucosuria, hypokalemia.in children with an overdose, inhibition of the hypothalamic-pituitary-adrenal system, Itsenko-Cushings syndrome, a decrease in the excretion of growth hormone, and an increase in intracranial pressure are possible.

Treatment: discontinuation of the drug, symptomatic therapy, if necessary - correction of electrolyte balance. There is no specific antidote.

Storage conditions

In the original packaging, in the refrigerator (at a temperature of 2-8 ° C).