Instructions Prednisolone-Darnitsa solution for injection 30 mg/ml ampoule 1 ml No. 3
Composition
active ingredient: prednisolone;
1 ml of solution contains prednisolone sodium phosphate equivalent to prednisolone - 30 mg;
Excipients: disodium edetate, sodium hydrogen phosphate dodecahydrate, potassium dihydrogen phosphate, ethanol 96%, propylene glycol, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear colorless or slightly colored liquid.
Pharmacotherapeutic group
Corticosteroids for systemic use. Glucocorticoids. ATC code H02A B06.
Pharmacological properties
Pharmacodynamics.
It has anti-inflammatory, anti-allergic, immunosuppressive, anti-shock and antitoxic effects. In relatively large 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. The anti-allergic and immunosuppressive properties of the drug are due to the 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 by 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 restoration of the sensitivity of vascular receptors to catecholamines and enhancement of 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 the stimulation of protein synthesis processes in the liver and the acceleration of the inactivation of endogenous toxic metabolites and xenobiotics in it, as well as with an increase in the stability of cell membranes, including hepatocytes.
Enhances glycogen deposition in the liver and glucose synthesis from protein metabolism products. Increased blood glucose levels activate insulin secretion. Inhibits glucose uptake by fat cells, which leads to activation of lipolysis. However, increased insulin secretion stimulates lipogenesis, which contributes to fat accumulation. Reduces intestinal calcium absorption, increases its leaching from bones and excretion by the kidneys. Inhibits the release of adrenocorticotropic hormone and β-lipotropin by the pituitary gland, and therefore, with prolonged use, the drug may contribute to the development of functional insufficiency of the adrenal cortex.
The main factors limiting long-term prednisone therapy are osteoporosis and Itsenko-Cushing syndrome. Prednisone 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 seizure threshold.
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 absorbed into the blood quickly, but compared to reaching the maximum level in the blood, the pharmacological effect of the drug is significantly delayed and develops 2-8 hours. In blood plasma, most of prednisolone binds to transcortin (cortisol-binding globulin), and when the process is saturated - to albumin. With a decrease in protein synthesis, a decrease in the binding capacity of albumins is observed, which can cause an increase in the free fraction of prednisolone and, as a result, the manifestation of its toxic effect when using conventional 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, as well as in the kidneys, small intestine, bronchi. Oxidized forms are glucuronized or sulfated and are excreted by the kidneys in the form of conjugates.
About 20% of prednisolone is excreted from the body by the kidneys in unchanged form, a small part is excreted in the bile.
In liver diseases, the metabolism of prednisolone slows down and the degree of its binding to blood plasma proteins decreases, which leads to an increase in the half-life of the drug.
Indication
Intramuscular, intravenous administration:
systemic connective tissue diseases: systemic lupus erythematosus, dermatomyositis, scleroderma, periarthritis nodosa, Bekhterev's disease;
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: Addison's crisis;
emergency conditions: severe forms of nonspecific ulcerative colitis and Crohn's disease, shock (burn, traumatic, surgical, anaphylactic, toxic, transfusion), asthmatic status, acute adrenal 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.
Contraindication
Parasitic and infectious diseases of viral, fungal or bacterial etiology, currently existing or recently transferred: herpes simplex, herpes zoster (viremic phase), chickenpox, measles; amebiasis, strongyloidiasis (established or suspected); systemic mycosis; active tuberculosis.
Post-vaccination period (duration 10 weeks: 8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.
Immunodeficiency states caused by HIV infection.
Diseases of the digestive tract: gastric and duodenal ulcers, esophagitis, gastritis, acute or latent peptic ulcer, recently performed intestinal anastomosis, nonspecific ulcerative colitis with the threat of perforation or abscess formation, diverticulitis.
Cardiovascular system diseases: recent myocardial infarction, decompensated chronic heart failure, arterial hypertension, predisposition to thromboembolic disease.
Endocrine system diseases: decompensated diabetes mellitus, thyrotoxicosis, hypothyroidism, Itsenko-Cushing's disease.
Severe chronic renal and/or hepatic failure (except for an emergency such as hepatic coma), nephrourolithiasis.
Hypoalbuminemia. Systemic osteoporosis. Myasthenia gravis. Severe myopathy. Productive symptoms in mental illnesses, psychoses. Obesity (III-IV century). Poliomyelitis (except for the form of bulbar encephalitis). Open- and closed-angle glaucoma, cataracts.
For intra-articular injections – infections at the injection site.
Interaction with other medicinal products and other types of interactions
When using prednisolone simultaneously with other drugs, it is possible:
with thyroid hormones, inducers of liver enzymes, in particular with barbiturates, phenytoin, pyrimidone, carbamazepine, rifampicin - weakening of the effects of prednisolone due to an increase in its systemic clearance;
with estrogens (including oral contraceptives containing estrogen), cyclosporine, CYP3A4 inhibitors, in particular erythromycin, clarithromycin, ketoconazole, diltiazem, aprepitant, itraconazole, oleandomycin - increased therapeutic and toxic effects of prednisolone;
with antacids – decreased absorption of prednisolone;
with salicylic acid derivatives and other nonsteroidal anti-inflammatory drugs - increased likelihood of gastric mucosal ulcers; prednisolone reduces the level of salicylic acid derivatives in the blood serum, increasing their renal clearance; the drug increases the risk of developing hepatotoxic reactions to paracetamol due to induction of liver enzymes and the formation of its toxic metabolite;
with cardiac glycosides - increased toxicity of the latter, and due to the resulting hypokalemia - increased risk of arrhythmias;
with hypoglycemic agents – inhibition of the hypoglycemic effect of oral hypoglycemic agents and insulin;
with antihypertensive drugs – reduced effectiveness of the latter;
with tricyclic antidepressants – increased symptoms of depression caused by taking prednisolone and increased intraocular pressure;
with immunosuppressants – increased risk of developing infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus;
with diuretics, laxatives, amphotericin B - increased risk of hypokalemia; prednisolone increases the risk of osteoporosis when used simultaneously with amphotericin and carbonic anhydrase inhibitors;
with m-cholinoblockers, antihistamines, nitrates - increased intraocular pressure and reduced effectiveness of antihistamines;
with neuroleptics, carbutamide, azathioprine - increased risk of cataract development;
with estrogens, anabolic drugs, oral contraceptives – manifestations of hirsutism and acne;
with live antiviral vaccines and against the background of other types of immunizations - increased risk of virus activation and development of infections;
with muscle relaxants against the background of hypokalemia - increased severity and duration of muscle blockade against the background of the use of muscle relaxants;
with anticholinesterase agents – the occurrence of muscle weakness in patients with myasthenia (especially in patients with myasthenia gravis);
with mitotane and other inhibitors of adrenal cortex function - may require an increase in the dose of the drug;
with antiemetics – increased antiemetic effect;
with isoniazid, mexiletine, praziquantel - a decrease in their plasma concentrations;
with somatotropin (in high doses) – a decrease in the effect of the latter;
with fluoroquinolones – tendon damage;
with cyclosporine - cases of seizures have been noted. Since the simultaneous administration of these drugs causes a mutual slowdown in metabolism, it is likely that seizures and other side effects associated with the use of each of these drugs, both in monotherapy and in their combined use, may occur more often. Combined use may cause an increase in the concentration of other drugs in the blood plasma.
With long-term therapy, prednisolone increases the content of folic acid.
The drug reduces the effect of vitamin D on the absorption of Ca2+ in the intestinal cavity.
Application features
For 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 agents.
The drug should be used with caution in cases of impaired carbohydrate tolerance.
If it is necessary to use prednisolone while taking oral hypoglycemic drugs or anticoagulants, it is necessary to adjust the dosage regimen of the latter.
In patients with thrombocytopenic purpura, the drug is used only intravenously.
Clinical examination should include examination of the cardiovascular system, X-ray examination of the lungs, examination of the stomach and duodenum, urinary system, and organs of vision. Laboratory examination should include: complete blood count, concentration of glucose in blood and urine, electrolytes in blood plasma.
When treated with glucocorticoids for a long time, it is recommended to regularly monitor blood pressure, determine the level of glucose in urine and blood, conduct a stool test for occult blood, analyze blood clotting parameters, X-ray control of the spine, and ophthalmological examination (once every 3 months).
Treatment with the drug, even at low doses, masks the signs and symptoms of pre-existing infections and those that develop during treatment (including opportunistic infections), making their diagnosis more difficult. During treatment, contact with people with colds or other infections should be avoided.
Children who have been in contact with measles or chickenpox patients during the treatment period should be prescribed specific immunoglobulins as a prophylaxis (within 10 days after contact).
Immunization should not be performed during treatment.
If patients experience unusual stressful situations during glucocorticoid treatment, it is recommended to increase the dose of short-acting corticosteroids before, during, and after the stressful situation.
You should not drink alcohol during treatment with prednisone.
Depending on the duration of treatment and dose, the drug may have a negative effect on calcium metabolism. Prevention of osteoporosis is recommended, which is especially important in patients with risk factors (including family history, advanced age, postmenopause, insufficient protein and calcium intake, excessive smoking, excessive alcohol consumption, and decreased physical activity). Prevention is based on adequate calcium and vitamin D intake, and also includes physical activity.
To reduce the side effects of prednisone therapy, it is justified to prescribe an appropriate diet.
When using high doses of prednisolone for a long period (30 mg/day for at least 4 weeks), reversible disorders of spermatogenesis may occur, which persist for several months after discontinuation of the drug.
In patients who have been receiving supraphysiological doses of prednisolone (approximately 7.5 mg prednisolone or equivalent) for more than 3 weeks, prednisolone treatment should be discontinued gradually. Treatment should be discontinued gradually, even if it has been for less than 3 weeks, for the following groups of patients:
– patients undergoing a repeated course of prednisolone treatment;
– patients who were prescribed a repeated course of treatment within a year after long-term treatment (months, years);
– patients receiving more than 40 mg/day of prednisolone or equivalent;
– patients with adrenal insufficiency not caused by exogenous corticosteroid administration.
After discontinuation of treatment, withdrawal syndrome, adrenal insufficiency, and exacerbation of the disease for which prednisolone was prescribed may occur. If functional adrenal insufficiency is observed after the end of prednisolone treatment, the drug should be resumed immediately, and the dose should be reduced very slowly and with caution (for example, the daily dose should be reduced by 2-3 mg over 7-10 days).
Adrenal cortical atrophy develops with prolonged therapy and may persist for many years after cessation of treatment.
Steroid-induced secondary adrenal insufficiency can be minimized by gradual dose reduction. This type of insufficiency may persist for several months after cessation of therapy, so any stressful situation that occurs during this period should prompt the resumption of corticosteroid therapy.
With sudden withdrawal, especially in the case of previous use of high doses, a withdrawal syndrome occurs, which is manifested by fever, decreased appetite, nausea, vomiting, diarrhea, lethargy, dizziness, generalized musculoskeletal pain, and asthenia.
Due to the risk of developing hypercorticism, a new course of cortisone treatment after a previous long-term treatment with prednisolone for several months should always be started with low initial doses (except for use for vital indications). It is prescribed with caution after a recent myocardial infarction (in patients with acute, subacute myocardial infarction, the spread of the focus of necrosis, slowing down the formation of scar tissue, rupture of the heart muscle are possible).
If there is a history of psoriasis, high doses of prednisolone should be used with extreme caution.
The drug should be used with extreme caution in cases of migraine and a history of certain parasitic diseases (especially amebiasis).
It is prescribed with extreme caution in immunodeficiency states (including AIDS or HIV infection).
In children during the growth period, glucocorticosteroids can be used only for absolute indications and under particularly careful supervision of a doctor.
In case of intercurrent infections and septic conditions, it is necessary to simultaneously administer antibiotic therapy.
Electrolyte balance should be monitored especially carefully when prednisolone is used in combination with diuretics. With prolonged treatment with prednisolone, potassium preparations and an appropriate diet should be prescribed to prevent hypokalemia due to the possible increase in intraocular pressure and the development of subcapsular cataracts.
Use in severe infectious diseases (not listed in the "Contraindications" section) is possible only against the background of specific antimicrobial therapy.
Women during menopause should be screened for possible osteoporosis.
In Addison's disease, concomitant administration of barbiturates should be avoided due to the risk of acute adrenal insufficiency (Addisonian crisis).
The drug should be used with extreme caution in hepatic and renal failure.
Special attention should be paid to the use of systemic corticosteroids in patients with existing or a history of severe affective disorders, including depressive, manic-depressive psychosis, and previous steroid psychosis. Patients and/or caregivers should be warned about the possibility of developing serious psychiatric side effects. Symptoms usually appear within a few days or weeks after starting treatment. The risk of these side effects is higher with high doses. Most reactions disappear after reducing the dose or discontinuing the drug, although specific treatment is sometimes necessary. If such symptoms develop, you should consult a doctor. Psychiatric disorders can also occur during glucocorticoid withdrawal.
Use during pregnancy or breastfeeding
The drug should not be used during pregnancy. If it is necessary to use the drug, breastfeeding should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients treated with prednisolone should refrain from potentially hazardous activities that require increased attention and speed of mental and motor reactions.
Method of administration and doses.
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 prednisolone depends on the severity of the disease.
For the treatment of adults, the daily dose is 4-60 mg intravenously or intramuscularly.
Children should be given the drug intramuscularly (deep into the gluteal muscle) strictly according to indications and under the supervision of a doctor: children aged 6-12 years - 25 mg/day, aged 12 years and older - 25-50 mg/day. The duration of use and the number of injections of the drug are determined individually.
In Addison's disease, the daily dose for adults is 4-60 mg intravenously or intramuscularly.
In severe form of nonspecific ulcerative colitis - 8-12 ml/day (240-360 mg of prednisolone) for 5-6 days, in severe form of Crohn's disease - 10-13 ml/day
(300-390 mg of prednisolone) for 5-7 days.
In emergency situations, prednisolone should be administered intravenously, slowly (over approximately 3 minutes) or drip, at a dose of 30-60 mg. If intravenous infusion is difficult, the drug should be administered intramuscularly, deeply. With this method of administration, the effect develops more slowly. If necessary, the drug should be re-administered intravenously or intramuscularly at a dose of 30-60 mg after 20-30 minutes.
In some cases, an increase in the specified dose is allowed, which is decided by the doctor 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 is administered every 3 days. The course of treatment is up to 3 weeks.
Children.
Use in children over 6 years of age only as directed and under the supervision of a physician. The dosage and duration of therapy are determined by the physician individually depending on the age and severity of the disease. With prolonged use in children, growth retardation is possible, therefore it is necessary to limit the use of minimum doses according to specific indications for the shortest possible time. The benefits of treatment must outweigh the possible risk of side effects.
Overdose
In case of overdose, nausea, vomiting, bradycardia, arrhythmia, worsening of heart failure, cardiac arrest, hypokalemia, increased blood pressure, muscle cramps, hyperglycemia, thromboembolism, acute psychosis, dizziness, headache, possible development of symptoms of hypercorticism: weight gain, development of edema, arterial hypertension, glucosuria, hypokalemia. In children, overdose may cause suppression of the hypothalamic-pituitary-adrenal system, Itsenko-Cushing syndrome, decreased excretion of growth hormone, increased intracranial pressure.
Treatment: discontinuation of the drug, symptomatic therapy, if necessary - correction of electrolyte balance. There is no specific antidote.
Adverse reactions
The development of serious adverse reactions depends on the dose and duration of treatment. Adverse reactions usually develop with prolonged treatment with the drug, during a short period the risk of their occurrence is unlikely.
Infections and infestations: masking of symptoms of bacterial, viral, fungal infections, opportunistic infections.
Blood and lymphatic system: increase in total leukocyte count with decrease in eosinophils, monocytes and lymphocytes. Lymphoid tissue mass decreases. Blood clotting, hypercoagulation may increase, leading to thrombosis, thromboembolism.
Endocrine system and metabolism: decreased glucose tolerance, "steroid" diabetes mellitus or manifestation of latent diabetes mellitus, increased need for insulin and oral hypoglycemic drugs, hyperlipidemia, suppression of the hypothalamic-pituitary-adrenal system, growth retardation in children and adolescents, delayed sexual development in children, menstrual disorders, impaired production of sex hormones (amenorrhea), postmenopausal bleeding, Itsenko-Cushing syndrome (moon face, pituitary obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae).
Metabolic:
negative nitrogen and calcium balance, mineral and electrolyte imbalance, hypokalemic alkalosis. Side effects due to the glucocorticosteroid activity of prednisolone: fluid and Na+ retention (peripheral edema), hypernatremia, hypokalemic syndrome - arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue.
Mental disorders: irritability, delirium, disorientation, euphoria, hallucinations, depression, paranoia, nervousness, restlessness, anxiety, sleep disorders, insomnia, euphobia, suicidal tendencies, labile mood, increased concentration, psychological dependence, mania, manic-depressive psychosis, exacerbation of schizophrenia, dementia, psychoses, epileptic seizures, cognitive dysfunction (including amnesia and impaired consciousness).
Nervous system: peripheral neuropathies, paresthesias, dizziness, headache, autonomic disorders, increased intracranial pressure accompanied by vomiting, cerebellar pseudotumor, seizures.
Organs 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 ocular viral and fungal infections, exophthalmos.
Cardiovascular system: arterial hypo- or hypertension, bradycardia, arrhythmia, asystole (due to rapid administration of the drug), development or increase in manifestations of chronic heart failure, atherosclerosis, thrombosis, vasculitis, peripheral edema, ECG changes characteristic of hypokalemia. In patients with acute and subacute myocardial infarction - spread of the focus of necrosis, slowing down the formation of a scar, which can lead to rupture of the heart muscle.
On the part of the immune system: hypersensitivity reactions, including rash, itching, urticaria, hyperemia, angioedema, anaphylactic shock.
Gastrointestinal tract: nausea, vomiting, flatulence, unpleasant taste in the mouth, dyspepsia, increased or decreased appetite, hiccups, epigastric pain, diarrhea, erosive esophagitis, peptic ulcers with perforation and bleeding, esophageal ulcer, esophageal candidiasis, pancreatitis, gallbladder perforation, gastric bleeding, local ileitis and ulcerative colitis. During the period of use of the drug, an increase in ALT, AST and alkaline phosphatase may be observed, which is usually not significant and reversible after discontinuation of the drug.
Skin and subcutaneous tissue: slowed regeneration process, petechiae, bruises, hematomas, ecchymoses, striae, thinning of the skin, hyper- or hypopigmentation, acne, tendency to pyoderma, skin atrophy, telangiectasias, acne, hirsutism, purpura, post-steroid panniculitis, characterized by the appearance of erythematous, hot subcutaneous thickenings within 2 weeks after drug withdrawal, Kaposi's sarcoma.
Musculoskeletal system: growth retardation and ossification processes in children (premature closure of epiphyseal growth plates), proximal myopathy, osteoporosis, muscle tendon rupture, muscle weakness, decreased muscle mass (atrophy), steroid myopathy, fractures of the spine and long bones, aseptic osteonecrosis, very rarely - pathological bone fractures.
General: malaise, persistent hiccups when using the drug in high doses, adrenal insufficiency leading to hypotension, hypoglycemia, and fatalities in stressful situations such as surgery, trauma, or infection if the prednisolone dose is not increased.
With sudden withdrawal of the drug, withdrawal syndrome is possible, the severity of symptoms depends on the degree of adrenal atrophy, headache, nausea, abdominal pain, dizziness, anorexia, weakness, mood swings, lethargy, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itching of the skin, weight loss. In more severe cases, severe mental disorders and increased intracranial pressure, steroid pseudorheumatism in patients with rheumatism, fatalities are observed.
Reactions at the injection site: pain, burning, pigmentation changes (depigmentation, leukoderma), skin atrophy, sterile abscesses, rarely – lipoatrophy.
Expiration date
2 years.
Storage conditions
Store in the original packaging, in a refrigerator (at a temperature of 2 ºС to 8 ºС).
Keep out of reach of children.
Incompatibility
Prednisolone should not be mixed and administered simultaneously with other drugs in the same infusion system or in the same syringe.
When mixing a solution of prednisolone with heparin, a precipitate forms.
Incompatible with aerosols of sympathomimetic agents for the treatment of bronchial asthma in children (risk of respiratory paralysis).
Packaging
1 ml in an ampoule; 3 or 5 ampoules in a contour blister pack; 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
