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

active substance:
prednisolone	5 mg
Excipients:
sucrose (refined sugar)	37.5 mg
lactose monohydrate (milk sugar)	105 mg
gelatin	1 mg
calcium stearate monohydrate	2.5 mg
potato starch	- a sufficient amount to prepare a tablet weighing 250 mg.

Description:Tablets are white in a flat-cylindrical form with a facet and a risk.

Pharmacotherapeutic group:glucocorticosteroid

ATX: & nbsp

H.02.A.B.06 Prednisolone

Pharmacodynamics:

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 (GCS) 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 inhibits the phospholipase A2, suppresses the liberation of arachidonic acid, and inhibits the biosynthesis of endoperoxides, leukotrienes, which promote inflammation, 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 and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: delays sodium ions (Na⁺) and water in the body, stimulates the excretion of potassium ions (K⁺) (mineralocorticosteroid activity), reduces the absorption of calcium ions (Ca²⁺) from the gastrointestinal tract, causes a "washing away" of calcium ions from the bones and an increase in its renal excretion, reduces the mineralization of bone tissue.

Immunodepressive effect is caused by involution of lymphoid tissue, 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 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 the effect is mainly due to the inhibition of inflammatory processes, the prevention or reduction of the degree of edema of the mucous membranes, the decrease in the eosinophilic infiltration of the submucosal layer of the bronchial epithelium and the deposition of circulating immune complexes in the bronchial mucosa, as well as the inhibition of erosion and desquamation of the mucosa. 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.

Suppresses the synthesis and secretion of ACTH and, again, the synthesis of endogenous GCS.

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% The drug binds to plasma proteins: transcortin (cortisol-binding globulin) 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% 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);

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

- rheumatic fever, acute rheumatic heart disease;

- bronchial asthma, asthmatic status;

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

- Skin diseases - pemphigus, psoriasis, eczema, atopic dermatitis (common neurodermatitis),contact dermatitis (with the defeat of a large surface of the skin), toxicermy, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous herpetiform dermatitis, Stevens-Johnson syndrome;

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

- allergic eye diseases: allergic forms of conjunctivitis;

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

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

- congenital adrenal hyperplasia;

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

- subacute thyroiditis;

- blood diseases and hematopoiesis system - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura,secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital (erythroid) hypoplastic anemia;

- interstitial lung diseases - acute alveolitis, pulmonary fibrosis, sarcoidosis II-III stage;

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

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

- multiple sclerosis;

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

- hepatitis;

- prevention of graft rejection during organ transplantation;

- hypercalcemia on the background of cancer;

- myeloma disease.

Contraindications:

For short-term use according to vital indications, a hypersensitivity to Prednisolone or the components of the drug, lactase deficiency, lactose intolerance, sugarase / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption, children up to 3 years of age.

Carefully:

With caution, the drug should be used in the following diseases and conditions:

- zabortion of the gastrointestinal tract - peptic ulcer of stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis;

- Parazitic, and infectious diseases of a viral, fungal or bacterial nature (current or recent, including recent contact with a 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 conditions (including AIDS or HIV infection);

- zcardiovascular system abolition, incl. uncompensated chronic heart failure, hypertension, hyperlipidemia;

- endokrinnye diseases - diabetes (including a violation of tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV c);

- tsevere chronic renal and / or hepatic insufficiency, nephrourolythiasis;

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

- fromsystemic osteoporosis, myasthenia gravis gravis, acute psychosis, poliomyelitis (with the exception of the form of bulbar encephalitis), open and closed angle glaucoma;

- bVariability.

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

Pregnancy and lactation:

At pregnancy in I and II trimester apply only on vital indications.

With prolonged therapy during pregnancy, there is a violation of fetal growth. In the third trimester of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy for the newborn.

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 from 3 years of age and older, the initial dose is 1-2 mg / kg of body weight per day in 4-6 receptions, maintaining - 0.3-0.6 mg / kg / 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.

Under stressful influences (infection, allergic reaction, trauma, surgery, nervous stress) 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).

Side effects:

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

When applying Prednisolone may be noted:

From the endocrine system: depression of glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Isenko-Cushing syndrome (lunate face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle, weakness, striae), delay of 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, hiccups, increased 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, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eyes, trophic changes in the cornea, exophthalmos.

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

Caused by mineralocorticosteroid activity - fluid retention and sodium ions 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 the growth and processes of ossification in children (premature closure of the epiphyseal growth zones), osteoporosis (pathological bone fractures, aseptic necrosis of the head of the humerus and thigh bone), rupture of muscle tendons, steroid myopathy, muscle loss (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, rapid nighttime urination, urolithiasis.

Overdose:

It is possible to increase dose-dependent side effects. It is necessary to reduce the dose of Prednisolone.

Treatment is symptomatic.

Interaction:

The simultaneous use of prednisolone with:

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

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

- from sodium-containing preparations - to the development of edema and increased blood pressure;

- amphotericin B - increased risk of heart failure;

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

- indirect anticoagulants - weakens (less intensifies) their effect (dose adjustment is required);

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

- ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) - the risk of erosive and ulcerative lesions in the gastrointestinal tract increases and bleeding develops (in combination with NSAIDs, a decrease in the dose of glucocorticosteroids due to the summation of the therapeutic effect is possible in the treatment of arthritis); paracetamol - the risk of hepatotoxicity increases (induction of "hepatic" enzymes and the formation of a toxic metabolite of paracetamol);

- 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);

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

- vitamin D - its effect on the absorption of calcium ions (Ca ²⁺) in the intestine; a somatotropic hormone - It reduces the effectiveness of the latter, and with praziquantel - its concentration;

- M-holinoblokatorami (including antihistamines and tricyclic antidepressants with m-cholinoblocking activity) and nitrates - promotes increased intraocular pressure;

- isoniazid and mexiletine - increases their metabolism (especially in "slow" acetylators), which leads to a decrease in their plasma concentrations.

Carboangidrase inhibitors and looped diuretics may increase the risk of osteoporosis.

Indomethacin, displacing prednisolone from association with albumin, increases the risk of developing its side effects.

Adrenocorticotropic hormone (ACTH) strengthens the action of prednisolone.

Ergocalciferol and parathyroid hormone prevent the development of osteopathy, caused by prednisolone.

Cyclosporine and ketoconazole, slowing the metabolism of prednisolone, can in some cases increase its toxicity.

Simultaneous application androgen and steroid anabolic drugs with prednisolone promotes the development of peripheral edema and hirsutism, the appearance of acne.

Estrogens and oral estrogen-containing contraceptives reduce the clearance of prednisolone, which may be accompanied by an increase in the severity of its action.

Mitotan and other inhibitors of adrenal cortex function may necessitate an increase in the dose of prednisolone.

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

Antipsychotic drugs (antipsychotics) and azathioprine increase the risk of developing cataracts with the use of prednisolone.

Immunosuppressive drugs increase the risk of infection and lymphoma or other lymphoproliferative disorders caused by the Epstein-Barr virus.

Simultaneous application antacids reduces the absorption of prednisolone.

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

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 concentration.

In order to reduce side effects, antacids can be used, and the intake of potassium ions (K +) into the body (diet, potassium preparations) can be increased.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 apply 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 a relative insufficiency of the adrenal cortex 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 Prednisolone should not be vaccinated due to a decrease in its effectiveness (immune response).

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

In children during prolonged treatment with prednisolone, careful monitoring of the dynamics of growth and development is necessary. Children who during the period of treatment were in contact with sick measles or chickenpox, prophylactically use specific immunoglobulins.

Due to a weak mineralocorticosteroid effect for replacement therapy with adrenal insufficiency Prednisolone used in combination with mineralocorticosteroids.

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.

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

During the period of application, it is necessary to refrain from driving and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, 5 mg.

Packaging:

For 20, 30, 50, 60 tablets in a polymer can.

For 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

One bank or 2, 3, 5, 6 contour mesh packages with instructions for use are placed in a cardboard box.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-000773

Date of registration:29.09.2011

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Representation: & nbspBIOSINTEZ JSC BIOSINTEZ JSC Russia

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Prednisolone (Prednisolon)