Prednisolonum

General characteristics. Structure:

Active ingredient: 00,1 g or 0,005 g of Prednisolonum.

Excipients: sucrose, potato starch, stearic acid.

Pharmacological properties:

Pharmacodynamics. Prednisolonum – synthetic glucocorticoid drug, the dehydrogenated hydrocortisone analog. Has an antiinflammatory, antiallergic, immunodepressive effect, increases sensitivity of beta adrenoceptors to endogenous catecholamines.

Interacts with specific cytoplasmatic receptors (receptors for glucocorticosteroids (GKS) are in all fabrics, especially their is a lot of in a liver) with formation of the complex inducing formation of proteins (including the enzymes regulating the vital processes in cells).

Protein metabolism: reduces amount of globulins in plasma, increases synthesis of albumine in a liver and kidneys (with increase in coefficient albumine/globulin), reduces synthesis and strengthens a protein catabolism in muscular tissue.

Lipidic exchange: increases synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat happens preferential in the field of a shoulder girdle, the person, a stomach), leads to development of a hypercholesterolemia.

Carbohydrate metabolism: increases absorption of carbohydrates from digestive tract; increases activity of glyukozo-6-phosphatase (increase in intake of glucose from a liver in blood); increases activity of a fosfoenolpiruvatkarboksilaza and synthesis of aminotransferases (activation of a gluconeogenesis); promotes development of a hyperglycemia.

Water элетролитный exchange: Na + and water in an organism detains, stimulates removal of K+ (mineralokortikoidny activity), reduces absorption of Ca2 + from digestive tract, reduces a mineralization of a bone tissue.

The antiinflammatory effect is connected with release oppression by eosinophils and mast cells of mediators of an inflammation; induction of formation of lipokortin and reduction of quantity of the mast cells producing hyaluronic acid; with reduction of permeability of capillaries; stabilization of cellular membranes (especially lizosomalny) and membranes of organellas. Affects all stages of inflammatory process: inhibits synthesis of prostaglandins at the level of arachidonic acid (липокортин oppresses A2 phospholipase, suppresses a liberation of arachidonic acid and inhibits biosynthesis of endoperoxides, the leukotrienes promoting processes of an inflammation, an allergy, etc.), synthesis of "pro-inflammatory cytokines" (Interlaken 1, a tumor necrosis factor an alpha, etc.); increases resistance of a cellular membrane to action of various disturbing factors.

The immunodepressive effect is caused by the caused involution of an adenoid tissue, oppression of proliferation of lymphocytes (especially T lymphocytes), suppression of migration of V-cells and interactions of T - and V-lymphocytes, braking of release of cytokines (interleykina-1, 2; gamma interferon) from lymphocytes and macrophages and decrease in antibody formation.

The antiallergic effect develops as a result of decrease in synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine, etc. biologically active agents, reduction of number of the circulating basophiles, suppression of development of adenoid and connecting tissue, reduction of number of T - and V-lymphocytes, mast cells, decrease in sensitivity of effector cells to mediators of an allergy, oppression of antibodyformation, change of an immune response of an organism.

At obstructive respiratory diseases action is caused, mainly, by braking of inflammatory processes, the prevention or reduction of expressiveness of hypostasis of mucous membranes, decrease in eosinophilic infiltration of a submucosal layer of an epithelium of bronchial tubes and adjournment in mucous bronchial tubes of the circulating cell-bound immune complexes, and also braking of an erozirovaniye and desquamation mucous. Increases sensitivity of beta adrenoceptors of bronchial tubes of small and average caliber to endogenous catecholamines and exogenous sympathomimetics, reduces viscosity of slime due to reduction of its products.

Suppresses synthesis and secretion of AKTG and for the second time – synthesis of endogenous GKS.

Slows down connective tissue reactions during inflammatory process and reduces a possibility of formation of cicatricial fabric.

Pharmacokinetics. At intake Prednisolonum is well soaked up from digestive tract. The maximum concentration in blood is reached in 1-1,5 h after oral administration. To 90% of drug contacts proteins of plasma: transcortinum (kortizolsvyazyvayushchy globulin) and albumine. Prednisolonum is metabolized in a liver, partially in kidneys and other fabrics, generally by conjugation with glucuronic and sulfuric acids. Metabolites are inactive.

It is removed with bile and with urine by glomerular filtering and for 80-90% it reabsorbirutsya by tubules. 20% of a dose are removed by kidneys in not changed look. Plasma elimination half-life after oral administration makes 2-4 hours.

Indications to use:

• General diseases of connecting fabric (system lupus erythematosus, scleroderma, nodular periarteritis, dermatomyositis, pseudorheumatism).
• Acute and chronic inflammatory diseases of joints – gouty and psoriasis arthritis, an osteoarthritis (including posttraumatic), polyarthritis (including senile), the humeroscapular periarthritis ankylosing a spondylarthritis (Bekhterev's disease), juvenile arthritis, Steel's syndrome at adults, a bursitis nonspecific tendosinovit, a synovitis and an epicondylitis.
• Acute rheumatism, rheumatic carditis, hysterical chorea.
• Bronchial asthma.
• Acute and chronic allergic diseases – including allergic reactions to medicines and foodstuff, a serum disease, a small tortoiseshell, allergic rhinitis, a Quincke's edema, a medicinal dieback, a pollinosis, etc.
• Skin diseases – a pemphigus, psoriasis, eczema, atopic dermatitis (widespread neurodermatitis), contract dermatitis (with defeat of a big surface of skin), a toxidermia, seborrheal dermatitis, exfoliative dermatitis, a toxic epidermal necrolysis (Lyell's disease), violent herpetiform dermatitis, Stephens-Johnson's syndrome.
• States after wet brain (including against the background of a tumor of a brain or connected with surgical intervention, radiation therapy or an injury of the head) after preliminary parenteral use.
• Allergic diseases of eyes – allergic forms of conjunctivitis.
• Inflammatory diseases of eyes – a sympathetic ophthalmia, heavy slow lobbies and back uveites, an optic neuritis.
• Primary or secondary adrenal insufficiency (including a state after removal of adrenal glands).
• Inborn adrenal struma.
• Diseases of kidneys of autoimmune genesis (including acute glomerulonephritis); nephrotic syndrome.
• Subacute thyroiditis.
• Diseases of blood and system of a hemopoiesis – an agranulocytosis, a panmyelopathia, autoimmune hemolitic anemia, lympho-and myeloid leukoses, лимфогрануломатоз, a Werlhof's disease, secondary thrombocytopenia at adults, an eritroblastopeniya (erythrocyte anemia), inborn (erythroidal) hypoplastic anemia.
• Intersticial diseases of lungs – an acute alveolitis, a pneumosclerosis, a sarcoidosis of the II-III St.
• Tubercular meningitis, a pulmonary tuberculosis, aspiration pneumonia (in a combination to specific chemotherapy).
• A berylliosis, Leffler's syndrome (which is not giving in to other therapy); lung cancer (in a combination with cytostatics).
• Multiple sclerosis.
• Gastrointestinal diseases – ulcer colitis, a disease Krone, local enteritis.
• Hepatitis, hypoglycemic states.
• Prevention of reaction of graft rejection at organ transplantation.
• A hypercalcemia against the background of oncological diseases, nausea and vomiting when performing cytostatic therapy.
• Multiple myeloma.

Route of administration and doses:

The dose of drug and duration of treatment is established by the doctor individually depending on indications and disease severity.

It is recommended to accept all daily dose of drug once or a double daily dose – every other day taking into account a circadian rhythm of endogenous secretion of glucocorticosteroids in the range from 6 to 8 o'clock in the morning. The high daily dose can be distributed on 2-4 receptions, at the same time in the mornings it is necessary to accept a high dose. A pill should be taken in time or directly after food, washing down with a small amount of liquid.

At acute states and as replacement therapy by the adult appoint 20-30 mg/days in an initial dose, the maintenance dose makes – 5-10 mg/days. If necessary the initial dose can make 15-100 mg/days, supporting – 5-15 mg/days.

For children the initial dose makes 1-2 mg/kg of body weight a day in 4-6 receptions, supporting – 300-600 mkg/kg a day.

When obtaining therapeutic effect the dose is gradually reduced – on 5 mg, then on 2,5 bucketed mg in 3-5 days, canceling at first later receptions. At long administration of drug the daily dose should be reduced gradually. Long therapy cannot be stopped suddenly! Cancellation of a maintenance dose is carried out by that more slowly, than glucocorticosteroid therapy was longer applied.

At stressful influences (an infection, allergic reaction, an injury, operation, a mental overload) in order to avoid an aggravation of a basic disease the dose of Prednisolonum has to be temporarily increased (in 1,5-3, and in hard cases – at 5-10 times).

Features of use:

Use during pregnancy and breastfeeding. At pregnancy (especially in 1 trimester) apply only according to vital indications. As glucocorticosteroids pass into breast milk, in case of need uses of drug during breastfeeding, feeding by a breast is recommended to be stopped.

During treatment by Prednisolonum (especially long) observation of the oculist, control of arterial pressure, a condition of water and electrolytic balance, and also a picture of peripheral blood and level of glucose of blood is necessary.

For the purpose of reduction of by-effects it is possible to appoint antacids, and also to increase receipt of K+ in an organism (a diet, potassium drugs). Food has to be protein-rich, vitamins, with restriction of content of fats, carbohydrates and table salt.

Effect of drug amplifies at patients with a hypothyroidism and cirrhosis. Drug can increase the existing emotional instability or psychotic disturbances. At the instruction to psychoses in the anamnesis Prednisolonum in high doses is appointed under strict control of the doctor.

With care it is necessary to apply at an acute and subacute myocardial infarction – distribution of the center of a necrosis, delay of formation of cicatricial fabric and a rupture of a cardiac muscle is possible.

In stressful situations during the supporting treatment (for example, surgeries, an injury or infectious diseases) it is necessary to carry out dose adjustment of drug in connection with increase in need for glucocorticosteroids.

It is necessary to watch carefully patients within a year after the end of long therapy with Prednisolonum in connection with possible development of relative insufficiency of bark of adrenal glands in stressful situations.

At sudden cancellation, especially in case of the previous use of high doses, development of a syndrome of "cancellation" (anorexia, nausea, block, generalized musculoskeletal pains, the general weakness), and also an exacerbation of a disease concerning which Prednisolonum was appointed is possible.

During treatment it is not necessary to carry out by Prednisolonum vaccination in connection with decrease in its efficiency (immune response).

Appointing Prednisolonum at intercurrent infections, septic states and tuberculosis, it is necessary to carry out treatment by antibiotics of bactericidal action at the same time.

At children during prolonged treatment by Prednisolonum careful observation of dynamics of growth and development is necessary. To children who during treatment were in contact with patients with measles or chicken pox preventively appoint specific immunoglobulins.

Owing to weak mineralokortikoidny effect for replacement therapy at adrenal insufficiency Prednisolonum is used in a combination from mineralokortikoida.

At patients with a diabetes mellitus it is necessary to control the content of glucose of blood and if necessary to korrigirovat therapy.

Radiological control of bone and joint system (pictures of a backbone, brush) is shown.

Prednisolonum with latent infectious diseases of kidneys and urinary tract is capable to cause a leukocyturia in patients that can have diagnostic value.

Prednisolonum increases the maintenance of metabolites 11 - and 17 - oxyketocorticosteroids.

Side effects:

Frequency of development and expressiveness of side effects depends on duration of use, size of the used dose and a possibility of observance of a circadian rhythm of purpose of Prednisolonum.

At use of Prednisolonum can be noted:
From endocrine system: decrease in tolerance to glucose, a steroid diabetes mellitus or manifestation of a latent diabetes mellitus, oppression of function of adrenal glands, an Icenco-Cushing syndrome (a crescent-shaped face, obesity of pituitary type, a hirsutism, increase in arterial pressure, a dysmenorrhea, an amenorrhea, muscular weakness, striya), a delay of sexual development at children.

From the alimentary system: nausea, vomiting, pancreatitis, steroid stomach ulcer and duodenum, erosive esophagitis, gastrointestinal bleedings and perforation of a wall of digestive tract, increase or loss of appetite, digestion disturbance, meteorism, hiccups. In rare instances – increase in activity of "hepatic" transaminases and an alkaline phosphatase.

From cardiovascular system: arrhythmias, bradycardia (up to a cardiac standstill); development (at predisposed patients) or strengthening of expressiveness of heart failure, ECG change characteristic of a hypopotassemia, increase in arterial pressure, hypercoagulation, fibrinferments. Patients with an acute and subacute myocardial infarction have a distribution of the center of a necrosis, delay of formation of cicatricial fabric that can lead to a rupture of a cardiac muscle.

From a nervous system: delirium, disorientation, euphoria, hallucinations, maniac-depressive psychosis, depression, paranoia, increase in intracranial pressure, nervousness or concern, sleeplessness, dizziness, вертиго, cerebellum pseudoneoplasm, headache, spasms.

From sense bodys: a back subkapsulyarny cataract, increase in intraocular pressure with possible injury of an optic nerve, tendency to development of consecutive bacterial, fungal or viral infections of eyes, trophic changes of a cornea, an exophthalmos.

From a metabolism: the increased calcium removal, a hypocalcemia, increase in body weight, negative nitrogenous balance (the increased disintegration of proteins), the increased perspiration.

Caused by mineralokortikoidny activity – a delay of liquid and sodium in an organism (peripheral hypostases), a hypernatremia, a gipokaliyemichesky syndrome (a hypopotassemia, arrhythmia, a mialgiya or a spasm of muscles, unusual weakness and fatigue).

From a musculoskeletal system: delay of growth and processes of ossification at children (premature closing of epiphyseal regions of growth), osteoporosis (it is very rare – pathological fractures of bones, an aseptic necrosis of a head humeral and a femur), a rupture of sinews of muscles, a steroid myopathy, decrease in muscle bulk (atrophy).

From integuments and mucous membranes: the slowed-down healing of wounds, petechias, ecchymomas, thinning of skin, hyper - or hypopigmentation, eels, striya, tendency to development of a pyoderma and candidiases.

Allergic reactions: skin rash, itch, acute anaphylaxis.

Others: development or an exacerbation of infections (emergence of this side effect is promoted jointly by the applied immunodepressants and vaccination), a leukocyturia, a syndrome of "cancellation".

Interaction with other medicines:

Co-administration of Prednisolonum with:
- inductors of "hepatic" microsomal enzymes (phenobarbital, rifampicin, Phenytoinum, theophylline, rifampicin, ephedrine) leads to decrease in its concentration;
- diuretics (especially "thiazide" and inhibitors of a karboangidraza) and Amphotericinum In can lead to strengthening of removal from an organism of K+ and increase in risk of development of heart failure;
- with natriysoderzhashchy drugs – to development of hypostases and increase in arterial pressure;
- cardiac glycosides – their portability worsens and the probability of development of ventricular premature ventricular contraction increases (because of the caused hypopotassemia);
- the hypopotassemia caused by GKS can increase expressiveness and duration of muscular blockade against the background of muscle relaxants;
- indirect anticoagulants – weakens (strengthens) their action less often (dose adjustment is required);
- anticoagulants and trombolitika – the risk of development of bleedings from ulcers in digestive tract increases;
- ethanol and non-steroidal anti-inflammatory drugs (NPVP) – the risk of emergence of erosive cankers in digestive tract and development of bleedings (in a combination with NPVP at treatment of arthritises the dose decline of glucocorticosteroids because of summation of therapeutic effect is possible) amplifies;
- paracetamol – the risk of development of a hepatotoxic (induction of liver enzymes and formation of a toxic metabolite of paracetamol) increases;
acetylsalicylic acid – accelerates its removal and reduces concentration in blood (at Prednisolonum cancellation the level of salicylates in blood increases and the risk of development of by-effects increases);
- insulin and peroral hypoglycemic drugs, antihypertensives – their efficiency decreases;
- vitamin D – its influence on absorption of Ca2 + in intestines decreases;
- somatotropic hormone – reduces efficiency of the last, and with prazikvantely – its concentration;
- M-holinoblokatorami (including antihistaminic drugs and tricyclic antidepressants) and nitrates – promotes increase in intraocular pressure;
- an isoniazid and mekselitiny – increases their metabolism (especially at "slow" atsetilator) that leads to decrease in their plasma concentration.

Inhibitors of a karboangidraza and "loopback" diuretics can increase risk of development of osteoporosis.

Indometacin, forcing out Prednisolonum from communication with albumine, increases risk of development of its side effects.

AKTG strengthens effect of Prednisolonum.

Ergocalciferol and parathormone interfere with development of the osteopathy caused by Prednisolonum.

Cyclosporine and кетоконазол, slowing down Prednisolonum metabolism, can increase its toxicity in some cases.

Co-administration of androgens and steroid anabolic drugs with Prednisolonum promotes development of peripheral hypostases and a hirsutism, appearance of eels.

Are oestrogenic and oral estrogensoderzhashchy contraceptives reduce clearance of Prednisolonum that can be followed by strengthening of expressiveness of its action.

Mitotanum and other inhibitors of function of bark of adrenal glands can cause need of increase in a dose of Prednisolonum.

At simultaneous use with live antiviral vaccines and against the background of other types of immunizations increases risk of activation of viruses and development of infections.

Antipsychotic means (neuroleptics) and Azathioprinum increase risk of development of a cataract at purpose of Prednisolonum.

Co-administration of antacids reduces Prednisolonum absorption.

At simultaneous use with anti-thyroid drugs decreases, and with thyroid hormones – the clearance of Prednisolonum increases.

Immunodepressants increase risk of development of infections and a lymphoma or other limfoproliferativny disturbances connected with Epstein's virus - Barrel.

At long therapy increases the content of folic acid.

Contraindications:

For short-term use according to vital indications the only contraindication is hypersensitivity to Prednisolonum or components of drug.

At children in a growth period of GKS have to be applied only according to absolute indications and under especially careful observation of the attending physician.

With care it is necessary to appoint drug at the following diseases and states:
- Digestive tract diseases – a peptic ulcer of a stomach and duodenum, an esophagitis, gastritis, an acute or latent round ulcer, recently created intestines anastomosis, nonspecific ulcer colitis with threat of perforation or abscessing, a diverticulitis.
- The parasitic and infectious diseases of the virus, fungal or bacterial nature (proceeding now or which are recently postponed including recent contact with the patient) – the herpes simplex surrounding herpes (a viremichesky phase), chicken pox, measles; amebiasis, strongyloidosis; system mycosis; active and latent tuberculosis. Use at serious infectious diseases is admissible only against the background of specific therapy.
- Pre-and the postvaccinal period (8 weeks to and 2 weeks after vaccination), lymphadenitis after BTsZh inoculation.
- Immunodeficiency (including AIDS or HIV infection).
- Diseases of cardiovascular system, including recently postponed myocardial infarction (at patients with an acute and subacute myocardial infarction distribution of the center of a necrosis, delay of formation of cicatricial fabric and, thereof, – a rupture of a cardiac muscle is possible), heavy chronic heart failure, arterial hypertension, a lipidemia.
- Endocrine diseases – a diabetes mellitus (including disturbance of tolerance to carbohydrates), a thyrotoxicosis, a hypothyroidism, Itsenko-Cushing's disease, obesity (the III-IV St).
- Heavy chronic renal and/or liver failure, нефроуролитиаз.
- The hypoalbuminemia and states contributing to its emergence.
- System osteoporosis, gravis myasthenia, acute psychosis, poliomyelitis (except for a form of bulbar encephalitis), open and closed-angle glaucoma.
- Pregnancy.

Overdose:

Strengthening of the by-effects described above is possible. It is necessary to reduce Prednisolonum dose.

Symptomatic treatment.

Storage conditions:

Period of validity - 2 years. Not to use after a period of validity. List B. In the place protected from light at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1 mg, 5 mg. On 10 tablets in a blister strip packaging. On 50, 60, 100 tablets in banks polymeric, or in glass jars. Each can or 2, 5, 10 blister strip packagings together with the application instruction in a pack.