Properties
What is it?
Composition: Active substance: prednisolone; 1 ml of solution contains prednisolone sodium phosphate, calculated as prednisolone 30 mg; excipients: disodium edetate, disodium phosphate dodecahydrate, potassium dihydrogen phosphate, ethanol 96%, propylene glycol, water for injection. Dosage form. Solution for injection. Main physicochemical properties: Clear, colorless or slightly colored liquid. Pharmacotherapeutic group. Corticosteroids for systemic use. Glucocorticoids. Prednisolone. ATC code H02AB06. Pharmacological properties. Pharmacodynamics. It has anti-inflammatory, anti-allergic, immunosuppressive, anti-shock, and antitoxic effects. In relatively high doses, it suppresses fibroblast activity, synthesis of collagen, reticuloendothelium, and connective tissue (inhibition of the proliferative phase of inflammation), inhibits synthesis and accelerates protein catabolism in muscle tissue, but increases its synthesis in the liver. The anti-allergic and immunosuppressive properties of the drug are due to the inhibition of lymphoid tissue development with its involution during prolonged use, a decrease in the number of circulating T and B lymphocytes, suppression of mast cell degranulation, and inhibition of antibody production. The anti-shock effect of the drug is due to increased vascular response to vasoconstrictive endo- and exogenous substances, restoration of vascular receptor sensitivity to catecholamines and enhancement of their hypertensive effect, as well as retention of sodium and water excretion from the body. The antitoxic effect of the drug is associated with the stimulation of protein synthesis processes in the liver and acceleration of the inactivation of endogenous toxic metabolites and xenobiotics in it, as well as increased stability of the cell membrane, including hepatocytes. It enhances glycogen deposition in the liver and glucose synthesis from protein metabolism products. An increase in blood glucose levels activates insulin secretion. It suppresses glucose uptake by fat cells, leading to activation of lipolysis. However, due to increased insulin secretion, lipogenesis is stimulated, which contributes to fat accumulation. It reduces calcium absorption in the intestines, increases its leaching from bones, and excretion by the kidneys. It suppresses the release of adrenocorticotropic hormone and B-lipotropin by the pituitary gland, which is why prolonged use of the drug can contribute to functional insufficiency of the adrenal cortex. The main factors limiting long-term therapy with prednisone are osteoporosis and Itsenko-Cushing's syndrome. Prednisolone suppresses the secretion of thyrotropic and follicle-stimulating hormones. In high doses, it can increase the excitability of brain tissue and reduce the threshold of convulsive readiness. It stimulates excessive secretion of hydrochloric acid and pepsin in the stomach, which can contribute to the development of peptic ulcers. Pharmacokinetics. When administered intramuscularly, it is rapidly absorbed into the blood, but compared to the maximum blood level, the pharmacological effect of the drug is significantly delayed and develops within 2-8 hours. In blood plasma, most of the prednisolone is bound to transcortin (cortisol-binding globulin), and when the process is saturated, it is bound to albumin. With a decrease in protein synthesis, a decrease in the binding capacity of albumins 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 usual therapeutic doses. The half-life in adults is 2-4 hours, in children it is shorter. It is biotransformed by oxidation, mainly in the liver. Also in the kidneys, small intestine, bronchi. Oxidized forms are glucuronidated or sulfated and excreted by the kidneys in the form of conjugates. Approximately 20% of prednisolone is excreted unchanged by the kidneys. A small portion is excreted with bile. In liver diseases, prednisolone metabolism slows down and its binding to blood plasma proteins decreases, leading to an increase in the drug's half-life. Clinical characteristics. Indications. Intramuscular, intravenous administration: systemic connective tissue diseases: systemic lupus erythematosus, dermatomyositis, scleroderma, nodular periarteritis, Bechterew's disease; - hematological diseases: acute hemolytic anemia, lymphogranulomatosis, granulocytopenia, thrombocytopenic purpura, agranulocytosis, various forms of leukemia; - skin diseases: common eczema, exudative multiform erythema, pemphigus vulgaris, erythroderma, exfoliative dermatitis, seborrheic dermatitis, psoriasis, alopecia, adrenogenital syndrome; - replacement therapy: Addisonian crisis; - emergencies: acute forms of nonspecific ulcerative colitis and Crohn's disease, shock (burn, traumatic, surgical, anaphylactic, toxic, transfusion), status asthmaticus, acute adrenal insufficiency, hepatic coma, acute allergic and anaphylactic reactions, hypoglycemic states. Intra-articular administration; chronic polyarthritis, osteoarthritis of large joints, rheumatoid arthritis. Post-traumatic arthritis, arthrosis. See blog: What is Prednisolone used for and how to use it? Contraindications. Hypersensitivity to the components of the drug. Diseases of parasitic and infectious nature of viral, fungal or bacterial origin, existing at the moment or recently transferred: herpes simplex, herpes zoster (viral phase), chickenpox, measles; amebiasis, strongyloidiasis (established or suspected), systemic mycosis, active tuberculosis. Post-vaccination period (duration 10 weeks: 8 weeks before vaccination and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency states caused by HIV infection. Diseases of the gastrointestinal tract: peptic ulcer disease of the stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, recent intestinal anastomosis, nonspecific ulcerative colitis with risk of perforation or abscess formation, diverticulitis. Cardiovascular diseases: recent myocardial infarction, decompensated chronic heart failure, arterial hypertension, predisposition to thromboembolic disease. Endocrine diseases: decompensated diabetes mellitus, thyrotoxicosis, hypothyroidism, Itsenko-Cushing's disease. Acute or chronic renal and/or liver failure (except for emergencies such as hepatic coma), nephrourolithiasis. Hypoalbuminemia. Systemic osteoporosis. Myasthenia gravis. Severe myopathy. Productive symptomatology in mental illnesses, psychosis. Obesity (III-IV degree). Poliomyelitis (except for the bulbar encephalitis form). Open and angle-closure glaucoma, cataracts. For intra-articular, periarticular injections and injections into tendon sheaths, where there is infection at the injection site or surrounding tissues. For injection directly into the tendon. For injection into the spine or other non-articular joints. Interaction with other medicinal products and other types of interaction. Concomitant treatment with CYP3A inhibitors, including products containing cobicistat, is expected to increase the risk of systemic side effects. Such a combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects; in this case, careful monitoring of the patient's condition is necessary. Possible reactions with simultaneous use of prednisolone with other drugs: thyroid hormones, liver enzyme inducers, particularly barbiturates, phenytoin, primidone, carbamazepine, rifampicin - weakening of the effect of prednisolone due to increased systemic clearance; with rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, primidone, ephedrine and aminoglutethimide - reduction of therapeutic effect due to increased metabolism of corticosteroids; with estrogens (including oral contraceptives containing estrogen), cyclosporine, CYP3A4 inhibitors, particularly erythromycin, clarithromycin, ketoconazole, diltiazem, aprepitant, itraconazole, oleandomycin - enhancement of therapeutic and toxic effects of prednisolone, so dose adjustment may be necessary; with etoposide - possible inhibition of metabolism by glucocorticosteroids in vitro. This can lead to an increase in both the efficacy and toxicity of etoposide, so monitoring is necessary; with antacids - decreased absorption of prednisolone; with salicylic acid derivatives and other non-steroidal anti-inflammatory drugs - increased probability of gastrointestinal bleeding and ulcer formation. Prednisolone reduces serum salicylate levels, increases their renal clearance, and steroid excretion can lead to salicylate intoxication. The drug increases the risk of developing hepatotoxic reactions to paracetamol due to induction of liver enzymes and formation of its toxic metabolite. Aspirin should be used with caution in patients with hypoprothrombinemia with glucocorticosteroids; with coumarin anticoagulants and warfarin - their effectiveness may be enhanced by concomitant corticosteroid therapy. Therefore, careful monitoring of the international normalized ratio (INR) or prothrombin time is necessary to avoid spontaneous bleeding; with cardiac glycosides - increased toxicity of the latter, and increased risk of arrhythmias due to resulting hypokalemia; with hypoglycemic agents - suppression of the hypoglycemic effect of oral antidiabetics and insulin; with tricyclic antidepressants - intensification of depression symptoms caused by prednisolone intake and increased intraocular pressure; with immunosuppressants - increased risk of developing infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus; with diuretics (loop, thiazide and acetazolamide), carbenoxolone, laxatives and antifungal agents (amphotericin B) - increased risk of hypokalemia, so concomitant use should be avoided. There is also an increased risk of hypokalemia with concomitant use of theophylline and with high doses of corticosteroids simultaneously with bambuterol, fenoterol, formoterol, ritodrine, salbutamol, salmeterol and terbutaline. Prednolone increases the risk of osteoporosis when used concomitantly with amphotericin and carbonic anhydrase inhibitors; with ketoconazole - reduced metabolic and renal clearance of methylprednisolone, which is also possible with prednisolone; with mifepristone - possible reduction of corticosteroid effect for 3-4 days; with methotrexate - possible increased risk of developing hematological toxicity; with m-cholino-blockers, antihistamines, nitrates - increased intraocular pressure and reduced efficacy of antihistamines; with neuroleptics, carbamide, azathioprine - increased risk of cataracts; with estrogens, anabolic agents, oral contraceptives - development of hirsutism and acne. Glucocorticoid effects may be enhanced, so dose adjustment may be necessary in this case; with live attenuated vaccines and other types of immunization - increased risk of virus activation and infection development. High doses of corticosteroids worsen the immune response, so live vaccines should be avoided (see section "Special Precautions"); with muscle relaxants in the background of hypokalemia - increased development and duration of muscle blockade with the use of muscle relaxants; with anticholinesterase agents - development of muscle weakness in patients with myasthenia (especially in patients with myasthenia gravis) and reduced effect on the X-ray contrast of cholecystography; with mitotane and other inhibitors of adrenal cortex function - can cause an increase in drug dosage; with antiemetics - increased antiemetic effect; with isoniazid, mexiletine, praziquantel - decreased plasma concentrations; with somatotropin (in high doses) - reduced effect of the latter; with erythromycin - can suppress the metabolism of some corticosteroids; with fluoroquinolones - tendon damage; with retinoids and tetracyclines - possible increase in intracranial pressure; with cyclosporine - increases plasma concentration of prednisolone. The same effect is possible with ritonavir. Cases of seizures have been reported, as concomitant administration of these drugs leads to a reciprocal slowing of metabolism, it is likely that seizures and other side effects associated with the use of each of these drugs, as well as their combined use, may occur more frequently. Combined use may lead to increased concentrations of other drugs in blood plasma. During long-term therapy, prednisolone increases folic acid content. The drug reduces the effect of vitamin D on Ca2+ absorption in the intestinal lumen. Special precautions. Anti-inflammatory/immunosuppressive effects and infection. Administer with extreme caution in immunodeficiency states (including AIDS or HIV infection). Treatment with the drug, even at low doses, masks the signs and symptoms of pre-existing infections and infections that develop during treatment (including opportunistic infections) and complicates their diagnosis. Therefore, contact with people with colds or other infections should be avoided during treatment. Suppression of inflammatory response and immune function increases susceptibility to infections and the severity of their course. New infections may occur during their use. Opportunistic infections that occur may be fatal. The clinical picture can often be atypical, and serious infections (such as sepsis and tuberculosis) can be masked and diagnosed at a progressive stage. In infectious diseases (not listed in the "Contraindications" section) and latent forms of tuberculosis, the drug should be prescribed only in combination with antibiotics and anti-tuberculosis drugs. Chickenpox is of particular concern, as this seemingly minor illness can be fatal for immunosuppressed patients. Patients (or parents of children) who have not had chickenpox should be advised to avoid close personal contact with patients with chickenpox or herpes zoster, and if they are exposed, they should seek immediate medical attention. Passive immunization with varicella/zoster (VZIG) immunoglobulin is necessary for patients who are not immune, who are receiving systemic corticosteroids, or who have used them in the previous 3 months. Patients who have been in contact with patients with measles or chickenpox during treatment should be given specific immunoglobulins for prophylaxis (within 10 days of contact). Special care and urgent treatment are required if chickenpox is diagnosed. Discontinuation of corticosteroids is not necessary, and dose increase may be possible. Immunization with live vaccines should not be carried out during treatment in individuals with impaired immune systems. Inactivated (killed) vaccines or toxoids can be used, but their efficacy may be reduced. Any intercurrent illness, during long-term therapy, as well as trauma or surgical manipulation, requires a temporary increase in dose. If corticosteroid use is discontinued after long-term therapy, a temporary need for their re-use may arise. In case of intercurrent infections, septic conditions, simultaneous antibiotic therapy is necessary. Use in severe infectious diseases (not indicated in the "Contraindications" section) is possible only on the background of specific antimicrobial therapy. Chronic immunosuppression (e.g., in organ transplantation) has been associated with an increased risk of malignancy. Discontinuation of use. In patients who have received doses higher than physiological doses of prednisolone (approximately 7.5 mg of prednisolone or equivalent) for more than 3 weeks, treatment should be discontinued gradually. Treatment should also be discontinued gradually even if it lasted less than 3 weeks for patient groups such as: patients undergoing a repeat course of prednisolone treatment; patients who have been prescribed a repeat course of treatment within one year after long-term treatment (months, years); patients receiving more than 40 mg of prednisolone or equivalent per day; patients with adrenal insufficiency not caused by exogenous corticosteroid intake; patients who have repeatedly taken corticosteroid doses in the evening. After discontinuation of treatment, withdrawal symptoms, adrenal insufficiency, and exacerbation of the disease for which prednisolone was prescribed may occur. If functional adrenal insufficiency is observed after completion of prednisolone treatment, it is necessary to urgently resume treatment with the drug, and dose reduction should be carried out very slowly and carefully (e.g., the daily dose should be reduced by 2-3 mg over 7-10 days). After reaching a daily dose of prednisolone of 7.5 mg, the dose reduction should be slower to allow the hypothalamus-pituitary-adrenal system to recover. Sudden discontinuation of systemic corticosteroid treatment for up to 3 weeks is advisable unless disease relapse is expected. Sudden withdrawal of up to 40 mg of prednisolone or equivalent daily dose for 3 weeks is unlikely to cause clinically significant suppression of the hypothalamus-pituitary-adrenal system in most patients. Adrenal cortex atrophy develops with long-term therapy and can persist for many years after discontinuation of treatment. Steroid-induced secondary adrenal insufficiency can be minimized by gradual dose reduction. This type of insufficiency can persist for several months after the end of therapy, so corticosteroid therapy should be resumed in any stressful situation that arises during this period. With sudden discontinuation, especially after previous high-dose use, a withdrawal syndrome occurs, manifested by fever, loss of appetite, nausea, vomiting, diarrhea, slowed behavior, dizziness, generalized bone-muscle pain, asthenia. Visual impairment. Visual disturbances may occur with systemic and local use of corticosteroids. If the patient experiences visual impairment or other symptoms of visual disturbance, it is advisable to refer the patient to an ophthalmologist for evaluation of possible causes, which may include cataracts, glaucoma, or rare diseases (such as central serous chorioretinopathy (CSCR), which have been reported after the use of systemic and topical corticosteroids). Scleroderma renal crisis Caution should be exercised in the treatment of patients with systemic sclerosis due to an increased (possibly fatal) frequency of renal crisis with hypertensive disease and also a decrease in urine output observed with daily doses of prednisolone of 15 mg or more. Therefore, blood pressure and kidney function (s-creatinine) should be checked regularly. If renal crisis is suspected, blood pressure should be carefully monitored. Elderly patients. General side effects of systemic corticosteroids may be associated with more serious consequences in the elderly, especially osteoporosis, hypertension, diabetes mellitus, predisposition to infections, and skin thinning. Careful clinical monitoring is necessary to prevent life-threatening reactions. Pediatric population. Since corticosteroids cause growth retardation in children and adolescents, which may be irreversible, use only according to absolute indications and under special medical supervision. Treatment should be limited to low doses for a short period to minimize suppression of the hypothalamus-pituitary-adrenal system and growth retardation (see section "Dosage and Administration"). Other warnings. Caution and regular monitoring are required during glucocorticosteroid treatment. Including prednisone, in patients with: diabetes mellitus or family history of diabetes; glaucoma or family history of glaucoma; hypertension or congestive heart failure; liver failure; epilepsy; osteoporosis - this is particularly important for women during menopause; history of severe affective disorders and especially those with a history of corticosteroid psychoses; peptic ulcer diseases; previous steroid myopathy; - renal failure; tuberculosis: affected or with radiological changes characteristic of tuberculosis. However, the occurrence of active tuberculosis can be prevented by prophylactic use of anti-tuberculosis therapy; recent myocardial infarction; hypothyroidism and existing chronic liver diseases (impaired function) - the effect of corticosteroids may be enhanced. Adrenal cortex atrophy, which develops with long-term therapy and can persist for many years after discontinuation of treatment. The drug should be used with caution in case of carbohydrate intolerance. If prednisolone is necessary, the dosage regimen of oral hypoglycemic agents or anticoagulants should be adjusted. In patients with thrombocytopenic purpura, the drug is used only intravenously. Depending on the duration of treatment and dosage, the drug may have a negative effect on calcium metabolism. Prophylaxis of osteoporosis is recommended, which is particularly important in patients with risk factors (including family history, old age, postmenopause, insufficient intake of protein and calcium, excessive smoking, excessive alcohol consumption, as well as reduced physical activity). Prophylaxis is based on adequate intake of calcium and vitamin D, and also includes physical activity. To reduce the side effects of prednisolone therapy, an appropriate diet is justified. With the use of high doses of prednisolone for long periods (at least 30 mg/day for at least 4 weeks), reversible disturbances in spermatogenesis may occur, which persist for several months after discontinuation of the drug. The drug should be used with extreme caution in renal and liver failure. Electrolyte balance should be carefully monitored, especially when prednisolone is taken concomitantly with diuretics. During long-term treatment with prednisolone, potassium preparations and an appropriate diet should be prescribed to prevent hypokalemia, due to possible increase in intraocular pressure and development of subcapsular cataracts. Due to the risk of hypercorticism development, a new course of cortisone treatment with prednisolone after prolonged treatment for several months should always be started with low initial doses (except for use according to vital signs). In Addison's disease, concomitant administration of barbiturates should be avoided due to the risk of acute adrenal insufficiency (Addisonian crisis). It is administered with caution after recent myocardial infarction (in patients with acute, subacute myocardial infarction, there may be spread of the necrosis focus, delayed scar formation, rupture of the heart muscle). In case of a history of psoriasis, high doses of prednisolone are used with extreme caution. If there is a history of seizures, prednisolone should be used only at the lowest effective dose. With extreme caution, the drug should be used for migraines, as well as if there is a history of certain parasitic diseases (especially amebiasis). Women during menopause should be examined for the possible development of osteoporosis. If patients experience unusual stressful situations during glucocorticosteroid treatment, it is recommended to increase the dose of rapid-acting corticosteroids before, during, and after the stressful situation. Special attention should be paid to the use of systemic corticosteroids in patients who have or have a history of severe affective disorders, including depressive, manic-depressive psychosis, previous steroid psychosis. There have been reports of Kaposi's sarcoma in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may lead to clinical remission. Alcohol consumption is not allowed during prednisolone treatment. Important information about excipients. This medicinal product contains sodium hydroxide, so patients on a sodium-controlled diet should exercise caution when using it. This medicinal product contains propylene glycol, which may cause symptoms similar to those caused by alcohol consumption. Use during pregnancy and lactation. Pregnancy. The ability of corticosteroids to cross the placenta varies between different drugs. However, 88% of prednisolone is inactivated when crossing the placental barrier. Administration of corticosteroids to pregnant animals can cause developmental abnormalities in the fetus, including cleft palate (harelip), intrauterine growth retardation, and effects on brain development. There is no evidence that corticosteroids increase the incidence of congenital anomalies such as cleft palate/lip in humans. However, when used for prolonged periods or multiple times during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation of the fetus. Hypoadrenalism may theoretically occur in newborns after prenatal exposure to corticosteroids, but it usually resolves spontaneously after birth and is rarely clinically significant. As with all drugs, corticosteroids should be prescribed only when the benefit to the mother and child outweighs the risks. However, when corticosteroids are necessary, patients with normal pregnancy can be treated as if they were not pregnant. Patients with pre-eclampsia or fluid retention require careful monitoring. Depression of hormone levels during pregnancy has been described. However, the significance of this finding is unclear. Breastfeeding. If the drug needs to be used, breastfeeding should be discontinued. Corticosteroids are excreted in breast milk in small amounts. However, daily doses of prednisolone up to 40 mg are unlikely to cause systemic effects in infants. In infants whose mothers receive higher doses, adrenal suppression may occur, but the benefits of breastfeeding may outweigh any theoretical risks. Monitoring of the infant for adrenal suppression is recommended. Ability to affect reaction rate when driving vehicles or operating other machinery. This medicinal product has little or no effect on the nervous system, so patients treated with prednisolone should refrain from potentially hazardous activities that require concentration and speed of mental and motor reactions. Method of administration and dosage. Prednisolone must not be mixed and administered simultaneously with other drugs in the same infusion system or syringe! The drug is intended for intravenous, intramuscular or intra-articular administration. The dose of prednisolone depends on the severity of the disease. For adult treatment, the daily dose is 4-60 mg intravenously or intramuscularly. For children, the drug should be administered intramuscularly (deep into the gluteal muscle) strictly according to indications and under medical supervision: for children aged 6-12 years, the daily dose is 25 mg, from 12 years - 25-50 mg/day. The duration of drug use and the number of administrations are determined individually. In Addison's disease, the daily dose in adults is 4-60 mg intravenously or intramuscularly. In severe nonspecific ulcerative colitis - 8-12 ml/day (240-360 mg prednisolone) for 5-6 days, in severe Crohn's disease - 10-13 ml/day (300-390 mg prednisolone) for 5-7 days. In emergencies, prednisolone should be administered intravenously slowly (approximately 3 minutes) or by drip infusion at a dose of 30-60 mg. If intravenous infusion is complicated, the drug should be administered intramuscularly, deeply. With this method of administration, the effect develops more slowly. If necessary, the drug is administered again intravenously or intramuscularly at a dose of 30-60 mg every 20-30 minutes. At the doctor's discretion, it is permissible to increase the indicated dose individually in each specific case. For adults, the dose of prednisolone for 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 should be administered every 3 days. The course of treatment is up to 3 weeks. Children. Used in children from 6 years of age only as prescribed by a doctor and under medical supervision. The duration of therapy and doses are determined by the doctor individually, depending on age and severity of the disease. With prolonged use in children, growth retardation is possible, so it is necessary to limit the use of minimum doses for specific indications for the shortest possible time. The benefits of treatment should outweigh the possible risk of side effects. Overdose. In case of overdose, nausea, vomiting, bradycardia, arrhythmia, increased heart failure, cardiac arrest, hypokalemia, increased blood pressure, muscle cramps, hyperglycemia, thromboembolism, acute psychosis, dizziness, headache, development of symptoms of hypercorticism (weight gain, edema, hypertension, glucosuria, hypokalemia) may occur. In children with overdose, suppression of the hypothalamus-pituitary-adrenal system, Itsenko-Cushing's syndrome, reduced growth hormone excretion, increased intracranial pressure may occur. Treatment: discontinuation of the drug, symptomatic therapy, correction of electrolyte balance if necessary. There is no specific antidote. Pediatric population. Increased intracranial pressure with optic disc edema in children (brain pseudotumor) usually appears after discontinuation of treatment. Growth retardation in children and adolescents. Shelf life. 2 years. Storage conditions. Store in the original packaging, in the refrigerator (at a temperature of 2°C to 8°C). Keep out of reach of children. Incompatibility. Prednisolone must not be mixed and administered simultaneously with other drugs in the same infusion system or syringe. Precipitation occurs when prednisolone and heparin solution are mixed. Incompatible with aerosol symptomatic agents for bronchial asthma in children (risk of respiratory paralysis). Packaging. Ampoule contains 1 ml; 3 or 5 ampoules are placed in a contour cell package; 1 (one) contour cell package is placed in a carton. Dispensing category. Pharmaceutical product group II, dispensed by prescription form №3 (dispensed without prescription in case of emergency).
