Prednisolone - instructions for use, dose, side effects, contraindications

Prednisolone is a synthetic glucocorticosteroid drug, a dehydrated analog of hydrocortisone. Has anti-inflammatory, antiallergic, immunosuppressive action, anti-shock effect, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

Interacts with specific cytoplasmic receptors (receptors for glucocorticosteroids are present in all tissues, especially in the liver), with the formation of a complex inducing the formation of proteins (including enzymes that regulate vital processes in cells).

The anti-inflammatory effect is associated with the suppression of the release of eosinophils and mast cells by inflammatory mediators; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in the permeability of capillaries; stabilization of cell membranes (especially lysosomal) and membranes of organelles.It works on all stages of the inflammatory process: it inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin depresses phospholipase A2, inhibits the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, promoting inflammation processes, allergies, etc.), the synthesis of "pro-inflammatory cytokines" (interleukin-1, tumor necrosis factor alpha, etc.) ; increases the resistance of the cell membrane to the action of various damaging factors.

Protein metabolism: reduces the number of globulins in plasma, increases the synthesis of albumins in the liver and kidneys (with increasing albumin / globulin ratio), reduces synthesis and enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat occurs mainly in the area of the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase (increased intake of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase andAminotransferase synthesis (activation gluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: retards sodium (Na⁺) And water in the body, it stimulates the excretion of potassium (Ka⁺) (mineralocorticoid activity), reduces the absorption of calcium (Ca²⁺) From the gastrointestinal tract, causing "washout" of calcium from the bones and increase its renal excretion, reduces bone mineralization. Immunosuppressive effect is caused by induced lymphoid tissue involution, suppression of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and interaction of T and B lymphocytes, inhibition of release of cytokines (interleukin-1, 2, gamma-interferon) from lymphocytes and macrophages and a decrease in the formation of antibodies.

Antiallergic effect develops as a result of decreased synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils, histamine, and others. bioactive substances, reducing the number of circulating basophils, suppression of lymphoid and connective tissues, reduce the number of T and B lymphocytes, mast cells,reducing the sensitivity of the effector cells to the mediators of allergy, inhibition of antibody production, changes in the immune response.

In obstructive airway diseases effect is due mainly the inhibition of inflammatory processes, prevention or reduction of severity of mucosal edema, reduction of eosinophil infiltration bronchial epithelium submucosal layer and deposition in the bronchial mucosa of circulating immune complexes and erozirovaniya inhibition and mucosal desquamation. Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchial tubes to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.

It inhibits the synthesis and secretion of adrenocorticotropic hormone (ACTH) and the second - the synthesis of endogenous glucocorticosteroids (GCS).

It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Pharmacokinetics:

Ingestion prednisolone well absorbed from the gastrointestinal tract.The maximum concentration in the blood is reached after 1-1.5 hours after oral administration. Up to 90% of the drug binds to plasma proteins: transcortin (cortisol-binding globulins) and albumins. Prednisolone metabolized in the liver, partially in the kidneys and other tissues, mainly by conjugation with glucuronic and sulfuric acids. Metabolites are inactive.

It is excreted with bile and kidneys by glomerular filtration and is reabsorbed by tubules by 80-90%. 20% of the dose is excreted by the kidneys unchanged. The half-life from plasma after oral administration is 2-4 hours.

Indications:

- Systemic diseases of connective tissue (systemic lupus erythematosus, scleroderma, nodular periarteritis, dermatomyositis, rheumatoid arthritis);

- aboutacute and chronic inflammatory diseases of the joints - gouty and psoriatic arthritis, osteoarthritis (including posttraumatic), polyarthritis, humeropathy periarthritis, ankylosing spondylitis (Bechterew's disease), juvenile arthritis, Still's syndrome in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis ;

- aboutrheumatic fever rheumatic fever, rheumatic carditis;

- brohnhialnaya asthma (severe form), asthmatic status;

- aboutacute and chronic allergic diseases - incl. allergic reactions to medicines and food products, serum sickness, urticaria, allergic rhinitis, Quincke's edema, drug exanthema, pollinosis, etc .;

- zskin abnormalities - pemphigus, psoriasis, eczema, atopic dermatitis (common neurodermatitis), contact dermatitis (with damage to the large surface of the skin), toxicermy, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell syndrome), bullous herpetiform dermatitis, Stevens-Johnson syndrome ;

- aboutbrain tissue (including on the background of a brain tumor or associated with surgery, radiation therapy or head trauma) after previous parenteral administration;

- aAllergic eye diseases: allergic forms of conjunctivitis;

- atocular diseases of the eye - sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis;

- PPrimary or secondary adrenal insufficiency (including the condition after removal of the adrenal glands);

- atborn adrenal hyperplasia;

- zkidney renal autoimmune genesis (including acute glomerulonephritis); nephrotic syndrome (including against a background of lipoid nephrosis);

- Pan erythematous thyroiditis;

- zblood ablation and hematopoiesis system - agranulocytosis, panmelopathy, autoimmune hemolytic anemia, acute lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital (erythroid) hypoplastic anemia;

- andInterspecial lung diseases - acute alveolitis, pulmonary fibrosis, sarcoidosis II-III st;

- ttuberculosis of meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy);

- beurythosis, Leffler's syndrome (not susceptible to other therapy); lung cancer (in combination with cytostatics);

- Rmultiple sclerosis;

- fgastrointestinal diseases - ulcerative colitis, Crohn's disease, local enteritis;

- gepatitis;

- Pthe prevention of graft rejection during organ transplantation;

- gиперкальциемия on the background of oncological diseases, nausea and vomiting during cytostatic therapy;

- mIelomnaya disease.

Contraindications:

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

The preparation contains lactose. Patients with rare hereditary diseases, such as lactose intolerance, lactose deficiency such as Lappa, or glucose-galactose malabsorption should not take the drug.

Carefully:

Carefully the drug should be prescribed in the following diseases and conditions:

- Diseases of the gastrointestinal tract - gastric ulcer and duodenal ulcers, esophagitis, gastritis, acute or latent peptic ulcer, recently established intestinal anastomosis, ulcerative colitis, with the threat of perforation or abscess, diverticulitis.

- Parasitic and infectious diseases of viral, fungal or bacterial nature (currently occurring or recently transferred, including recent contact with the patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidiasis; systemic mycosis; active and latent tuberculosis.The use in severe infectious diseases is permissible only against the background of specific therapy.

- Pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency (including AIDS or HIV infection).

- Diseases of the cardiovascular system, incl. recent myocardial infarction (in patients with acute and subacute myocardial infarction it is possible to spread the focus of necrosis, slow the formation of scar tissue and, as a result, break the heart muscle), decompensated chronic heart failure, hypertension, hyperlipidemia.

- Endocrine diseases - diabetes (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV c).

- Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis.

- Hypoalbuminemia and conditions predisposing to its occurrence (cirrhosis of the liver, nephrotic syndrome).

- Systemic osteoporosis, myasthenia gravis gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open and closed angle glaucoma.

- Pregnancy.

In children during growth, glucocorticosteroids should be used only in absolute indications and under the close supervision of the treating physician.

Pregnancy and lactation:

During pregnancy (especially in I trimester) are used only for vital indications.

Since glucocorticosteroids pass into breast milk, if it is necessary to use the drug during breastfeeding, it is recommended to stop breastfeeding.

Dosing and Administration:

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

The entire daily dose of the drug is recommended to take a single or double daily dose - every other day, taking into account the circadian rhythm of the endogenous secretion of glucocorticosteroids in the interval from 6 to 8 am. A high daily dose can be divided into 2-4 doses, with a large dose taken in the morning. Tablets should be taken orally during or immediately after meals, with a small amount of liquid.

In acute conditions and as a substitute therapy for adults appoint an initial dose of 20-30 mg / day, the maintenance dose is 5-10 mg / day. If necessary, the initial dose may be 15-100 mg / day, supporting - 5-15 mg / day.

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

When the therapeutic effect is obtained, the dose is gradually reduced - 5 mg, then 2.5 mg at intervals of 3-5 days, canceling at first later receptions. With prolonged use of the drug, the daily dose should be reduced gradually. Long-term therapy can not be stopped suddenly! The withdrawal of the maintenance dose is slower the longer the glucocorticosteroid therapy is used.

In case of stressful influences (infection, allergic reaction, trauma, surgery, mental overload) to avoid exacerbation of the underlying disease, the dose of prednisolone should be temporarily increased (at 1.5-3, and in severe cases 5-10 times).

In case of missed dose should take the drug as soon as possible, if the next time is approaching, forget the missed dose. Do not take a double dose at once.

Side effects:

The frequency of development and severity of side effects depends on the duration of the application,the magnitude of the dose used and the possibility of observing the circadian rhythm of prednisolone administration.

When applying Prednisolone may be noted:

From the endocrine system: depression of glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, oppression of the adrenal gland function, Itenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delay in sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding and perforation of the gastrointestinal wall, increased or decreased appetite, digestive disorders, flatulence, hiccough. In rare cases, an increase in the activity of "liver" transaminases and alkaline phosphatase.

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis.In patients with acute and subacute myocardial infarction-the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the sense organs: posterior subcapsular cataract, an increase in the eye pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral eye infections, trophic corneal changes, exophthalmos.

From the side of metabolism: increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Due to mineralocorticoid activity - fluid and sodium retention in the body (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the side of the musculoskeletal system: slowing growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare - pathological fractures, aseptic necrosis of the humeral head and femur), rupture of tendons of muscles, steroid myopathy, loss of muscle mass (atrophy).

From the skin and mucous membranes: delayed healing of wounds, petechiae, ecchymosis, thinning of the skin, hyper- or hypopigmentation, acne, striae, a tendency to develop pyoderma and candidiasis.

Allergic reactions: skin rash, itching, anaphylactic shock.

Other: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

Overdose:

It is possible to strengthen the above described side effects. It is necessary to reduce the dose of prednisolone. Treatment is symptomatic.

Interaction:

Simultaneous prescription of prednisolone:

- with inducers of "hepatic" microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) - leads to a decrease in its concentration;

- with diuretics (especially "thiazide" and inhibitors of carbonic anhydrase) and amphotericin B - can lead to increased excretion of K⁺;

- with sodium-containing drugs - to the development of edema and increased blood pressure;

- from amphotericin B - increased risk of heart failure;

- from cardiac glycosides - their tolerance is worsened and the likelihood of developing ventricular extrasystole (due to induced hypokalemia) increases;

- with indirect anticoagulants - prednisolone enhances the anticoagulant effect of coumarin derivatives;

- from anticoagulants and thrombolytics - Increased risk of bleeding from ulcers in the gastrointestinal tract;

- with ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) - increased risk of erosive and ulcerative lesions in the gastrointestinal tract and development of bleeding (in combination with NSAIDs in the treatment of arthritis may reduce the dose of glucocorticosteroids due to the summation of the therapeutic effect);

- from paracetamol - the risk of hepatotoxicity increases (induction of "hepatic" enzymes and the formation of a toxic metabolite of paracetamol);

- with acetylsalicylic acid - accelerates its removal and reduces the concentration in the blood (with the withdrawal of prednisolone, the level of salicylates in the blood increases and the risk of side effects increases);

- with insulin and oral hypoglycemic drugs, antihypertensive drugs - their effectiveness decreases;

- from vitamin D - decreases its effect on the absorption of Ca²⁺ in the intestine;

- from a somatotropic hormone - reduces the effectiveness of the latter, and with praziquantel - its concentration;

- from m-holinoblokatorami (including antihistamines and tricyclic antidepressants) and nitrates - promotes increased intraocular pressure;

- with isoniazid and mexiletine - increases the metabolism of isoniazid, mexiletine (especially in "fast" acetylators), which leads to a decrease in their plasma concentrations;

- with inhibitors of carbonic anhydrase and Amphotericin B - increase the risk of osteoporosis;

- with indomethacin - displacing prednisolone from association with albumin, increases the risk of its side effects;

- with adrenocorticotropic hormone (ACTH) - Strengthens the action of prednisolone;

- with ergocalciferol and parathyroid hormone - prevent the development of osteopathy, caused by prednisolone;

- with cyclosporine and ketoconazole - ciclosporin (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.

- the emergence of hirsutism and acne is facilitated by the simultaneous use of other steroid hormonal drugs (androgens, estrogens, anabolic, oral contraceptives);

- with estrogens and oral estrogen-containing contraceptives - reduce the clearance of prednisolone, which may be accompanied by an increase in the severity of its therapeutic and toxic effects;

- with mitotane and other inhibitors of the function of the adrenal cortex - may necessitate an increase in the dose of prednisolone;

- with simultaneous application with living antiviral vaccines and against the background of other types of immunizations - increases the risk of virus activation and the development of infections;

- from antipsychotic drugs (antipsychotics) and azathioprine - increase the risk of developing cataracts in the appointment of prednisolone.

Simultaneous appointment antacids reduces the absorption of prednisolone.

When used simultaneously with antithyroid drugs decreases, and with thyroid hormones - the clearance of prednisolone increases.

With immunosuppressive drugs - increase the risk of infection and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus.

Tricyclic antidepressants may increase the severity of depression caused by taking glucocorticosteroids (not shown for the therapy of these side effects).

Increases (with prolonged therapy) the content of folic acid.

Hypokalemia caused by glucocorticosteroids may increase the severity and duration of muscle blockade against the background of muscle relaxants. In high doses reduces the effect of somatropin.

Special instructions:

Before the beginning of treatment (if it is impossible due to the urgency of the condition - during the treatment), the patient should be examined for possible contraindications. Clinical examination should include examination of the cardiovascular system, radiology examination of the lungs, examination of the stomach and duodenum, urinary system, vision organs; the control of the formula of blood, the content of glucose and electrolytes in the blood plasma.

During treatment with prednisolone (especially long-term) it is necessary to observe the oculist, control blood pressure, condition of water-electrolyte balance, as well as patterns of peripheral blood and blood glucose levels.

In order to reduce side effects, antacids can be prescribed, as well as increase the intake of K + into the body (diet, potassium preparations). Food should be rich in proteins, vitamins, with a restriction of fat, carbohydrates and table salt. The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis. The drug may enhance existing emotional instability or psychotic disorders. When referring to a psychosis in an anamnesis prednisolone in high doses prescribed under the strict supervision of a doctor.

In stressful situations during maintenance treatment (for example, surgical operations, trauma or infectious diseases), a correction of the dose of the drug should be made in connection with an increase in the need for glucocorticosteroids. Patients should be monitored carefully during the year after the end of long-term therapy with prednisolone in connection with the possible development of relative adrenocortical insufficiency in stressful situations.

In case of sudden cancellation, especially in case of prior application of high doses, it is possible to develop the "withdrawal" syndrome (anorexia, nausea, block, generalized musculoskeletal pain, general weakness), as well as an exacerbation of the disease for which it was prescribed prednisolone.

During treatment with prednisolone, vaccination should not be given due to a decrease in its effectiveness (immune response).

Assigning prednisolone with intercurrent infections, septic states and tuberculosis, it is necessary to simultaneously perform antibiotic treatment of bactericidal action.

Children during prolonged treatment with prednisolone should carefully monitor the dynamics of growth. Children who were in contact with sick measles or chickenpox during the treatment period prophylactically prescribe specific immunoglobulins.

Due to a weak mineralocorticoid effect for replacement therapy with adrenal insufficiency prednisolone used in combination with mineralocorticoids.

Patients with diabetes should monitor blood glucose and, if necessary, correct therapy.An x-ray control of the osteoarticular system (images of the spine, hands) is shown.

Prednisolone in patients with latent infectious diseases of the kidneys and urinary tract can cause leukocyturia, which can have diagnostic value.

Prednisolone increases the metabolites content of 11- and 17-oxyketocorticosteroids.

In Addison's disease, simultaneous administration of barbiturates should be avoided - the risk of acute adrenal insufficiency (addisonic crisis).

Special precautions for the destruction of unused medicinal product

Drugs should not be disposed of in sewers or in household waste containers. Ask the pharmacist how to dispose of the unused medication. These activities will help protect the environment

Effect on the ability to drive transp. cf. and fur:

Some adverse reactions (cramps, dizziness, headache, impaired vision, mental disorders) can affect the ability to drive vehicles and mechanisms. During the use of the drug should not engage in the above activities.

Form release / dosage: Tablets, 5 mg.

Packaging:

30 tablets in a glass bottle.

One bottle with instructions for use is placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013537 / 01

Date of registration:05.03.2010

Date of cancellation:2017-03-28

The owner of the registration certificate:Pabianicki Pharmaceutical Plant Polfa, JSCPabianicki Pharmaceutical Plant Polfa, JSC Poland

Manufacturer: & nbsp

PABIANICE PHARMACEUTICAL WORKS POLFA Poland

Representation: & nbspPABYNITSKY PHARMACEUTICAL FACTORY POLFA JSC PABYNITSKY PHARMACEUTICAL FACTORY POLFA JSC Poland

Information update date: & nbsp28.03.2017

Illustrated instructions

Instructions

Prednisolone (Prednisolon )