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

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

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

Protein metabolism: reduces the number of globulins in plasma, increases the synthesis of albumin 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 (activationgluconeogenesis); promotes the development of hyperglycemia.

Water-electrolyte exchange: delays Na⁺ and water in the body, stimulates the excretion of K⁺ (mineralocorticoid activity), reduces the absorption of Ca²⁺ from the gastrointestinal tract, reduces the mineralization of bone tissue.

Anti-inflammatory effect is associated with inhibition 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 capillary permeability, stabilization of cell membranes (especially lysosomal ones) and organelle membranes. It acts on all stages of the inflammatory process: it inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin depresses phospholipase A2, inhibits the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, promoting 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.

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 and interleukin-2, gamma-interferon) from lymphocytes and macrophages and a decrease in the formation of antibodies.

Antiallergic effect develops as a result of reduced synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils histamine and other biologically active substances, decrease in the number of circulating basophils, T- and B-lymphocytes, mast cells; suppression of the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to mediators of allergy, inhibition of antibody formation, changes in the immune response of the body.

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.

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

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

Pharmacokinetics:

When administered orally prednisolone well absorbed from the gastrointestinal tract. The maximum concentration in the blood (C_mOh) is achieved after 1-1.5 hours after oral administration. Up to 90% The drug binds to plasma proteins: transcortin (cortisol-binding globulin) and albumins.

Prednisolone is 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 urine by glomerular filtration and is reabsorbed by tubules by 80-90%. 20% of the dose is excreted by the kidneys unchanged. The half-life (T_1/2) after oral administration is 2-4 hours, after intravenous administration - 2-3 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 (including senile), 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 (severe form), 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 .;

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

- edema of the brain (incl.on a background of a brain tumor or associated with surgery, radiation therapy or head trauma) after the preliminary parenteral administration of HA C;

- allergic eye diseases: allergic conjunctivitis, allergic marginal ulcers of the cornea;

- inflammatory eye diseases: 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;

- 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;

- lung diseases: acute alveolitis, pulmonary fibrosis, sarcoidosis II-III degree;

- tuberculous meningitis, fulminant or disseminated 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, nausea and vomiting during cytostatic therapy;

- myeloma disease.

Contraindications:

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

In children during the growth period, SCS should be used only in absolute indications and under the strictest supervision of the attending physician.

Carefully:

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

- diseases 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;

- parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, 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 states (including AIDS or HIV infection);

- diseases of the cardiovascular system (including recent myocardial infarction - in patients with acute and subacute myocardial infarction may spread necrosis, slowing the formation of scar tissue and thereby, - tearing of the heart muscle), severe chronic cardiac insufficiency, arterial hypertension, hyperlipidemia);

- endocrine diseases - diabetes (including violation of tolerance to carbohydrates), hyperthyroidism, hypothyroidism, Cushing's disease, obesity (III-IV degree);

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

- hypoalbuminemia and conditions predisposing to its occurrence;

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

- pregnancy.

Pregnancy and lactation:

When pregnancy (especially in the first trimester) is used only for life indications.

Since glucocorticosteroids penetrate 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 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.

With prolonged use of the drug, the daily dose should be reduced gradually. Long-term therapy can not be stopped suddenly!

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: a decrease in 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, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the side of the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of heart failure, changes in the electrocardiogram, 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, propensity to develop secondary bacterial, fungal or viral infections of the eyes, trophic corneal changes, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal concha, scalp possibly the deposition of drug crystals in the vessels of the eye),

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

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

From 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 wound healing, petechiae, ecchymoses, skin thinning, hyper- or hypopigmentation, steroid acne, striae, propensity to develop pyoderma and candidiasis.

Allergic reactions: skin rash, itching, anaphylactic shock, local allergic reactions.

Local reactions with parenteral administration: burning, numbness, pain, tingling at the injection site, infections at the injection site, rarely - necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with intramuscular injection (especially dangerous is the introduction to the deltoid muscle).

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. In this case, the dose of Prednisolone should be reduced.

Treatment: symptomatic.

Interaction:

The simultaneous administration of prednisolone with:

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

· diuretics (especially "thiazide" and inhibitors carbonic anhydrase) and amphotericin B - can lead to increased excretion from the body K⁺ and an increased risk of developing heart failure, as well as osteoporosis;

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

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

· indirect anticoagulants - weakens (less often - 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 the development of bleeding (in combination with NSAIDs in the treatment of arthritis, a dose of glucocorticosteroids may be reduced due to the summation of the therapeutic effect);

· 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 is reduced;

· vitamin D - its effect on the absorption of Ca decreases²⁺ in the intestine; somatotropic hormone - reduces the effectiveness of the latter, and with praziquantel - its concentration;

· M-holinoblokatorami (including antihistamines and tricyclic antidepressants) 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.

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

ACTH strengthens the action of prednisolone.

Hypokalemia caused by prednisolone may increase the severity and duration of muscle blockade in the background muscle relaxants.

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

Cyclosporin, inhibiting the metabolism of prednisolone, and ketoconazole, reducing its clearance, increase the toxicity of prednisolone.

Simultaneous appointment 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 live 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 in the appointment of prednisolone.

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 GCS (not shown for the therapy of these side effects).

Simultaneous appointment antacids reduces the absorption of prednisolone.

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

Long-term therapy with prednisolone raises the content folic acid.

Special instructions:

During treatment with prednisolone (especially prolonged), 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 level.

In order to reduce side effects, antacids can be prescribed, as well as increased intake of K⁺ in 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.

With caution should be used in acute and subacute myocardial infarction - possibly spreading the focus of necrosis, slowing the formation of scar tissue and rupture of the heart muscle.

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 response to an increase in the need for GCS.

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.

After the cancellation of long-term treatment with Prednisolone, the relative adrenocortical cortex remains relatively weak for several months. If during this period there are stressful situations, temporarily appoint GCS (according to indications), if necessary in combination with mineralocorticoids.

In Addison's disease, simultaneous administration of barbiturates due to the risk of acute adrenal insufficiency (addisonic crisis) should be avoided. During treatment Prednisolone should not be vaccinated 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.

In children during prolonged treatment with prednisolone, careful monitoring of the dynamics of growth and development is necessary. 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.

Form release / dosage:

Tablets, 5 mg.

Packaging:

For 10, 20 tablets per blister AL / PVC. For 1, 2, 5, 10 blisters in a cardboard box together with instructions for use.

For 100 tablets in a plastic bag. For 1 package together with instructions for use in a white plastic bottle with a snap-in lid of the same material.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014592 / 01

Date of registration:13.10.2008

The owner of the registration certificate:M. J. Biofarm Pvt. Ltd.M. J. Biofarm Pvt. Ltd. India

Manufacturer: & nbsp

M.J. BIOPHARM, Pvt. Ltd. India

Representation: & nbspM.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group M.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group India

Information update date: & nbsp29.08.2015

Illustrated instructions

Instructions

Prednisolone (Prednisolon )