PREDNISOLONUM

General characteristics. Structure:

Active ingredient: 1 ml of solution contains phosphate sodium Prednisolonum in terms of Prednisolonum – 30 mg;

excipients: sodium hydrophosphate anhydrous, sodium dihydrophosphate a dihydrate, propylene glycol, water for injections.

Main physical and chemical properties: transparent colourless or almost colourless solution.

Pharmacological properties:

Pharmacodynamics. Renders antiinflammatory, antiallergic, immunodepressive, antishock and anti-toxic effect. In rather high doses activity of fibroblasts, synthesis of collagen, a reticuloendothelium and connecting fabric (braking of a proliferative phase of an inflammation) oppresses, synthesis detains and accelerates a protein catabolism in muscular tissue, but increases its synthesis in a liver.

Antiallergic and immunosuppressive properties of drug are caused by braking of development of an adenoid tissue with its involution at prolonged use, decrease in number of the circulating T - and V-lymphocytes, oppression of degranulation of mast cells, suppression of products of antibodies. Antishock effect of drug is caused by increase in reaction of vessels on endo-and exogenous vasoconstrictive substances, with recovery of sensitivity of receptors of vessels to catecholamines and strengthening of their hypertensive effect, and also a delay of removal from an organism of sodium and water.

Anti-toxic effect of drug is connected with stimulation in a liver of processes of synthesis of protein and acceleration of an inactivation in it endogenous toxic metabolites and xenobiotics, and also with increase in stability of cellular membranes, including hepatocytes. Strengthens in a liver deposition of a glycogen and synthesis of glucose from products of protein metabolism. Increase in level of glucose in blood activates release of insulin.

Glucose capture by lipoblasts oppresses that leads to activation of a lipolysis. However, owing to increase in secretion of insulin there is a stimulation of a lipogenesis that promotes fat accumulation. Reduces absorption of calcium in intestines, increases washing away it from bones and excretion kidneys. Suppresses release by a hypophysis of adrenocorticotropic hormone and b-lipotropina in this connection at prolonged use drug can promote development of functional insufficiency of bark of adrenal glands. The main factors limiting long therapy with Prednisolonum are osteoporosis and Itsenko's syndrome – Cushing.

Prednisolonum oppresses secretion of thyritropic and follicle-stimulating hormones. In high doses can increase excitability of tissues of brain and promote reduction of the threshold of convulsive readiness. Stimulates supersecretion of hydrochloric acid and pepsin in a stomach in this connection can promote development of a round ulcer.

Pharmacokinetics. At intramuscular introduction it is soaked up in blood quickly, however in comparison with achievement of the maximum level in blood the pharmacological effect of drug considerably is late and 2-8 hours develop. In plasma the most part of Prednisolonum contacts transcortinum (kortizolsvyazyvayushchy globulin), and at process saturation – albumine. At decrease in synthesis of protein decrease in the connecting ability of albumine is observed that can cause increase in free fraction of Prednisolonum and, as a result, manifestation of its toxic action at use of usual therapeutic doses. The elimination half-life at adults – 2-4 hours, at children – is shorter. It Biotransformirutsya by oxidation preferential in a liver, and also in kidneys, a small bowel, bronchial tubes. The oxidized forms glyukuronizirutsya or sulphated and in the form of conjugates are removed by kidneys. About 20% of Prednisolonum are excreted from an organism by kidneys in not changed look; a small part – is allocated with bile. At liver diseases metabolism of Prednisolonum is slowed down and decreases extent of its linkng with proteins of plasma that leads to increase in an elimination half-life of drug.

Indications to use:

Intramuscular, intravenous administration: general diseases of connecting fabric: system lupus erythematosus, dermatomyositis, scleroderma, nodular periarteritis, Bekhterev's disease; hematologic diseases: gostry hemolitic anemia, lymphogranulomatosis, granulocytopenia, Werlhof's disease, agranulocytosis, various forms of leukemia;

skin diseases: usual eczema, multiformny exudative erythema, pemphigus usual, erythrosis, exfoliative dermatitis, seborrheal dermatitis, psoriasis, allopecia, adrenogenital syndrome; replacement therapy: Addisonov crisis;

medical emergencies: severe forms of nonspecific ulcer colitis and disease Krone, shock (burn, traumatic, operational, anaphylactic, toxic, transfusion), asthmatic status, acute insufficiency of bark of adrenal glands, hepatic coma, heavy allergic and anaphylactic reactions, hypoglycemic reactions;

Intra joint introduction: chronic polyarthritis, osteoarthritis of big joints, pseudorheumatism, posttraumatic arthritis, arthrosis;

Route of administration and doses:

Mixing and simultaneous use of Prednisolonum with other medicines in the same infusional system or the syringe is not allowed! Drug is appointed for intravenous, intramusculary or intra joint introduction. The dose of Prednisolonum depends on disease severity. For treatment of adults the daily dose makes 4-60 mg intravenously or intramusculary. To children drug is appointed intramusculary (deeply in a gluteus) strictly according to indications and under control of the doctor: to children at the age of 6-12 years – 25 mg/days, are more senior than 12 years – 25–50 mg/days. Duration of use and the number of administrations of drug is defined individually. At Addison's disease the daily dose for adults makes 4-60 mg intravenously or intramusculary.

At a severe form of nonspecific ulcer colitis on 8–12 ml/days (240-360 mg of Prednisolonum) within 5-6 days, at a severe form of a disease Krone – on 10-13 ml/days (300-390 mg of Prednisolonum) within 5-7 days. At medical emergencies Prednisolonum is entered intravenously, slowly (approximately within 3 minutes) or kapelno, in a dose of 30-60 mg. If intravenous injection is complicated, the drug is administered intramusculary, deeply. At this way of introduction the effect develops more slowly. If necessary the drug is administered repeatedly intravenously or intramusculary in a dose of 30-60 mg in 20-30 min. Increase in the specified dose is in some cases assumed that the doctor individually in each case solves. The adult Prednisolonum dose at intra joint introduction makes 30 mg for big joints, 10-25 mg – for joints of average size and 5-10 mg – for small joints. The drug is administered by each 3 days. A course of treatment – up to 3 weeks.

Features of use:

At infectious diseases and latent forms of tuberculosis it is necessary to appoint drug only in a combination with antibiotics and antituberculous remedies. In need of use of Prednisolonum against the background of reception of peroral gipoglikemiziruyushchy drugs or anticoagulants it is necessary to adjust the mode of dosing of the last. At patients with a Werlhof's disease drug is used only intravenously. After the termination of treatment emergence of a withdrawal, insufficiency of adrenal glands, and also an exacerbation of a disease in connection with which Prednisolonum was appointed is possible.

If after the end of treatment Prednisolonum observes functional insufficiency of adrenal glands, it is necessary to resume immediately drug use, and to carry out reduction of a dose very slowly and with care (for example, the daily dose needs to be reduced by 2-3 mg on an extent of 7-10 days). Because of danger of development of a hypercorticoidism the new course of treatment, after the carried-out earlier prolonged treatment by Prednisolonum on an extent of several months, always needs to be begun with a cortisone with low initial doses (except for acute states, life-threatening).

It is necessary to control especially carefully electrolytic balance at the combined use of Prednisolonum with diuretics. At prolonged treatment Prednisolonum for the purpose of prevention of a hypopotassemia it is necessary to appoint drugs of potassium and a sootvetstuyushchy diet in connection with possible increase in intraocular pressure and risk of development of a subkapsulyarny cataract. During treatment, especially long, необхимо observation of the oculist. At instructions on psoriasis in the anamnesis Prednisolonum in high doses is applied with extra care. If in the anamnesis there is psychosis, spasms, Prednisolonum it is necessary to apply only in minimal effective doses.

With special care it is necessary to appoint drug at migraine, existence in the anamnesis of data on some parasitic diseases (especially an amebiasis). To children Prednisolonum is appointed with special care. With special care appoint at immunodeficiency (including at AIDS or HIV infection). Also with care appoint after recently postponed myocardial infarction (at patients with an acute, subacute myocardial infarction expansion of the center of a necrosis, delay of formation of rubtsevy fabric, a rupture of a cardiac muscle is possible). With special care appoint at a liver failure, states which cause emergence of a hypoalbuminemia, obesity ІІІ - degree ІV. Women during a menopause need to pass researches of rather possible developing of osteoporosis.

At treatment glucocorticoids throughout a long time recommend to control regularly arterial pressure, to determine glucose level in urine and blood, to carry out the analysis a calla on the occult blood, analyses of indicators of coagulability of blood, radiological control of a backbone. Before an initiation of treatment glucocorticoids it is necessary to conduct careful examination of digestive tract for an exception of a peptic ulcer of a stomach and a duodenum.

Side effects:

Development of heavy side reactions depends on a dose and on treatment duration. Side reactions usually develop at prolonged treatment by drug. Throughout the short period the risk of their emergence is improbable. Infections and invasions: hypersensitivity to bacterial, viral, fungal infections, their weight with masking of symptoms, opportunistic infections. System of blood and lymphatic system: increase in total quantity of leukocytes at decrease in quantity of eosinophils, monocytes and lymphocytes. The mass of an adenoid tissue decreases. A blood coagulation which leads to fibrinferments, thromboembolisms can increase.

Endocrine system and metabolism: oppression гипоталамо - pituitary and adrenal system, delay of growth at children and teenagers, disturbance of a menstrual cycle, disturbance of secretion of sex hormones (amenorrhea), postclimacteric bleedings, the cushingoid person, a hirsutism, increase in body weight, decrease in tolerance to carbohydrates, increase in need for insulin and peroral sugar-lowering drugs, a lipidemia, negative balance of nitrogen and to calcium, increase in appetite, disturbance of mineral exchange and electrolytic balance, a gipokaliyemichesky alkalosis, a hypopotassemia, the delay of liquid and sodium in an organism is possible.

Mental disturbances: irritability, an eufobiya, a depression, tendency to a suicide, sleeplessness, labile mood, increase in concentration, psychological dependence, a mania, hallucinations, an exacerbation of schizophrenia, dementia, psychoses, uneasiness, a sleep disorder, epileptic attacks, cognitive dysfunction (including amnesia and disturbance of consciousness), increase in intracranial pressure which is followed by nausea and hypostasis of a disk of an optic nerve at children.

Nervous system: increase in intracranial pressure, epileptic attacks, periferichny neuropathy, paresthesias, dizziness, headache, vegetative disturbances.

Organs of sight: increase in intraocular pressure, glaucoma, puffiness of an optic nerve, cataract, thinning of a cornea and sclera, exacerbation of eye viral and fungal infections, exophthalmos.

Cardiovascular system: a myocardial gap owing to a myocardial infarction, arterial hypo - or hypertensia, bradycardia, the combined ventrikulyarny arrhythmia, an asystolia (owing to bystry administration of drug), atherosclerosis, thrombosis, a vasculitis, heart failure, peripheral hypostases.

Immune system: allergic reactions which cause an acute anaphylaxis with a lethal outcome angionevrotichny swelled, allergic dermatitis, change of reaction to skin tests, a tuberculosis recurrence, immunosuppression.

Digestive tract: nausea, swelling, unpleasant smack in a mouth, dyspepsia, round ulcers with perforation and bleeding, a gullet ulcer, gullet candidiasis, pancreatitis, perforation of a gall bladder, gastric bleeding, a local ileitis and ulcer colitis. Throughout use of drug increase in ALT, NUCLEAR HEATING PLANT and an alkaline phosphatase can be observed that usually is not important and it is reversible after drug withdrawal. Skin: regeneration delay, a skin atrophy, formation of hematomas and atrophic strips of skin (striya), a teleangiectasia, acne rash, an acne, a hirsutism, microhemorrhages, an ecchymoma, a purpura, hypo - or a hyperpegmentation, a post-steroid panniculitis which is characterized by emergence of an eritematoz, hot hypodermic thickenings for 2 weeks after drug withdrawal, Kaposha's sarcoma.

Musculoskeletal system: proximal myopathy, osteoporosis, rupture of sinews, mishechny weakness, atrophy, myopathy, spinal fractures and long bones, aseptic osteonecrosis. Urinary system: increase in risk of formation of urolites and the maintenance of leukocytes and erythrocytes in urine without explicit injury of kidneys.

The general: an indisposition, a resistant hiccups at use of drug in high doses, insufficiency of adrenal glands that leads to arterial hypotension, a hypoglycemia and lethal outcomes in stressful situations, such as surgical intervention, an injury or an infection if the dose of Prednisolonum is not increased. At sharp drug withdrawal are possible a withdrawal, weight of symptoms depends on degree of an atrophy of adrenal glands, the headache, nausea, an abdominal cavity pain, a glovokruzheniye, anorexia, weakness, changes of mood, a lethargy, fervescence, a mialgiya, an arthralgia, rhinitis is observed, konjyuktivit, a pain syndrome of skin, loss of body weight. In more hard cases – heavy mental disturbances and increase in intracranial pressure, a steroid pseudorheumatism at patients with rheumatism, death. Reactions on site introductions: pain, burning, pigmentation change (a depigmentation, a leukoderma), a skin atrophy, sterile abscesses, it is rare - a lipoatrophia.

Interaction with other medicines:

Anticoagulants: at simultaneous use with glucocorticoids effect of anticoagulants can amplify or decrease. Parenteral administration of Prednisolonum causes thrombolytic action of antagonists of vitamin K (флуиндион, аценокумарол). Salicylates and other non-steroidal anti-inflammatory drugs: simultaneous use of salicylates, indometacin and other non-steroidal anti-inflammatory drugs can increase probability of formation of ulcers of a mucous membrane of a stomach. Prednisolonum reduces the level of salicylates in blood serum, increasing their renal clearance.

Care at reduction of a dose of Prednisolonum at prolonged simultaneous use is necessary. Hypoglycemic drugs: Prednisolonum partially oppresses hypoglycemic effect of peroral antihyperglycemic means and insulin. Inductors of liver enzymes, for example, barbiturates, Phenytoinum, pyramidon, carbamazepine and римфампицин increase system clearance of Prednisolonum, thus reducing effect of Prednisolonum almost twice. CYP3A4 inhibitors, for example, erythromycin, кларитромицин, кетоконазол, diltiazem, an aprepitant, итраконазол and Oleandomycinum increase elimination and level of Prednisolonum in a blood plasma that strengthens therapeutic and side effects of Prednisolonum. Estrogen can potentsiirovat effect of Prednisolonum, slowing down his metabolism. It is not recommended to regulate Prednisolonum doses to the women applying oral contraceptives which promote not only to increase in an elimination half-life, and and development of atypical immunosuppressive effect of Prednisolonum.

Ftorkhinolona: simultaneous use can lead to injury of sinews. Amphotericinum, diuretics and purgatives: Prednisolonum can increase removal of potassium from an organism at patients who receive at the same time these drugs. Immunodepressants: Prednisolonum has active immunosuppressive properties which can cause increase in therapeutic effects or risk of development of different side reactions at simultaneous use with other immunodepresant. Only some of them can be explained with pharmacokinetic vzaimodeystiya. Glucocorticoids increase antiemetic efficiency of antiemetic drugs which are used in parallel at therapy by the antineoplastic drugs causing vomiting. Corticosteroids can increase concentration of a takrolimus in plasma at their simultaneous use, at their cancellation concentration of a takrolimus in plasma decreases. Immunization: glyukortikoida can reduce efficiency of immunization and increase risk of neurologic complications. Use of therapeutic (immunosuppressive) doses of glucocorticoids with live virus vaccines can increase risk of development of viral diseases. Throughout therapy vaccines of the emergency type can be applied by drug.

Antikholinesterazny means: use of glucocorticoids and antikholinesterazny means can cause muscular weakness in patients with a myasthenia, especially patients with a myasthenia have gravis. Others: it was reported about two serious cases of an acute myopathy at patients of advanced age who accepted a doksokarium chloride and Prednisolonum in high doses. At long therapy glucocorticoids can umenshat effect of Somatotropinum. Cases of emergence of an acute myopathy at use of corticosteroids for patients who at the same time receive treatment by neuromuscular transmission blockers are described (for example, панкурониум). At simultaneous use of Prednisolonum and cyclosporine cases of developing of spasms were noted. As simultaneous administration of these drugs causes mutual braking of metabolism probably that spasms and other side effects connected using everyone from these drugs as monotherapies at their simultaneous use can arise more often. Simultaneous use can cause increase in concentration of other drugs in plasma. Antihistaminic medicines reduce effect of Prednisolonum. At simultaneous use of Prednisolonum with hypotensive drugs decrease in efficiency of the last is possible.

Contraindications:

Hypersensitivity to drug components; a peptic ulcer of a stomach and duodenum, osteoporosis, Itsenko-Cushing's disease, tendency to a thrombembolia, a renal failure, arterial hypertension, viral infections (including virus damages of eyes and skin), a dekompensirovanny diabetes mellitus, the vaccination period (not less than 14 days before carrying out preventive immunization), lymphadenitis after vaccination of BTsZh, an active form of tuberculosis, glaucoma, a cataract, productive symptomatology at mental diseases, psychoses, depressions; system mycosis, herpetic diseases, syphilis, a heavy myopathy (except for myasthenias), poliomyelitis (except for a bulbar and encephalitic form), the period of pregnancy and feeding by a breast. For intra joint injections – infections in an injection site.

Overdose:

Symptoms. In case of overdose nausea, vomiting, bradycardia, arrhythmia, strengthening of the phenomena of heart failure, a cardiac standstill are possible; a hypopotassemia, increase in arterial pressure, a myotonia, a hyperglycemia, a thrombembolia, acute psychosis, dizziness, a headache, development of symptoms of a hypercorticoidism is possible: increase in body weight, development of hypostases, arterial hypertension, glucosuria, hypopotassemia. At children at overdose oppression гипоталамо - pituitary and adrenal system, an Icenco-Cushing syndrome, decrease in excretion of a growth hormone, increase in intracranial pressure is possible. There is no specific antidote.

Treatment: drug phase-out, symptomatic therapy, at a neobkhidimost – correction of electrolytic balance.

Storage conditions:

To store in the place protected from light at a temperature from 8 °C to 15 °C.

Issue conditions:

According to the recipe

Packaging:

On 1 ml or 2 ml of solution of drug in an ampoule. On 3, 5 or 10 ampoules in a pack.