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

Prednisolone is a synthetic glucocorticoid drug, a dehydrated analog of hydrocortisone.Has anti-inflammatory, antiallergic, desensitizing, anti-shock, antitoxic and immunosuppressive action.

Interacts with specific cytoplasmic receptors and forms a complex penetrating into the nucleus of the cell, stimulates the synthesis of matrix ribonucleic acid (mRNA); the latter induces the formation of proteins, incl. lipocortin, mediating cellular effects. Lipocortin depresses phospholipase A2, inhibits the release of arachidonic acid and suppresses the synthesis of prostaglandins, leukotrienes, which promote inflammation, allergies, etc.

Suppresses the release of the adrenocorticotropic hormone by the pituitary gland and, secondarily, the synthesis of endogenous glucocorticosteroids. Inhibits the secretion of thyroid-stimulating and follicle-stimulating hormones.

Reduces the number of lymphocytes and eosinophils, increases - erythrocytes (stimulates the production of erythropoietins).

Protein metabolism: reduces the amount of protein in the plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumins in the liver and kidneys; enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat 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, leading to an increase in the intake of glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases; leading to activation of gluconeogenesis.

Water-electrolyte exchange: retards sodium and water in the body, stimulates the excretion of potassium (mineralocorticoid activity), reduces the absorption of calcium from the gastrointestinal tract, "flushes" calcium from the bones, increases its excretion by the kidneys.

Anti-inflammatory effect is associated with inhibition of eosinophils and mast cells release of inflammatory mediators, inducing lipocortin formation and reducing the number of mast cells producing hyaluronic acid; with a decrease in capillary permeability, stabilization of cell membranes and membranes of organelles (especially lysosomal ones).

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

In obstructive airway diseases the action is mainly based on the inhibition of inflammatory processes, the inhibition of development or prevention of edema of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of bronchial epithelium, and the deposition of circulating immune complexes in the mucosa of the bronchi. There is inhibition of erosion and desquamation of the mucous membrane. Prednisolone increases the sensitivity of beta-adrenergic receptors of bronchi of small and medium caliber to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus due to oppression or reduction of its production.

Anti-shock and antitoxic action is associated with an increase in blood pressure (by increasing the concentration of circulating catecholamines and restoring the sensitivity of adrenoreceptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane-protective properties, activation of liver enzymes involved in the metabolism of endo- and xenobiotics.

The immunosuppressive effect is due to inhibition of the proliferation of lymphocytes (especially T-lymphocytes), suppression of B-cell migration and interaction of T and B lymphocytes, inhibition of cytokine release (interleukin-1, interleukin-2, gamma-interferon) from lymphocytes and macrophages and decreased education antibodies.

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

Pharmacokinetics:

Absorption is high, the maximum concentration in the blood with oral intake is reached after 1-1.5 hours. In plasma up to 90% of prednisolone binds to proteins: transcortin (cortisol-binding globulin) and albumins.

Metabolised in the liver, kidneys, small intestine, bronchi.Oxidized forms are glucuronized or sulphated. Metabolites are inactive. Half-life is 2-4 hours. It is excreted with bile and urine by glomerular filtration and is reabsorbed by tubules by 80-90%. 20% is excreted by the kidneys unchanged.

Indications:

Endocrine disorders: primary and secondary adrenal insufficiency (including the condition after removal of the adrenal glands); congenital adrenal hyperplasia; subacute thyroiditis.

Systemic connective tissue diseases: rheumatoid arthritis; systemic lupus erythematosus; dermatomyositis; scleroderma; nodular periarteritis.

Rheumatic fever, acute rheumatic heart disease.

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

Acute and chronic allergic diseases: allergic reactions to medicines and food; drug exanthema; serum sickness; hives; Pollinosis; angioedema; allergic rhinitis.

Bronchial asthma, asthmatic status.

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

Skin diseases: pemphigus; eczema, psoriasis, exfoliative dermatitis; atopic dermatitis; diffuse neurodermatitis; contact dermatitis (with the defeat of a large surface of the skin); Toxidermy; seborrheic dermatitis; toxic epidermal necrolysis (Lyell's syndrome); bullous herpetiform dermatitis; malignant exudative erythema (Stevens-Johnson syndrome).

Allergic and Inflammatory Diseases of the Eyes: allergic ulcers of the cornea; allergic forms of conjunctivitis; sympathetic ophthalmia; severe sluggish anterior and posterior uveitis; optic neuritis.

Diseases of the gastrointestinal tract: ulcerative colitis, Crohn's disease; hepatitis; local enteritis.

Lung cancer (in combination with cytostatic drugs).

Myeloma disease.

Lung diseases: acute alveolitis, pulmonary fibrosis, sarcoidosis II-III stage.

Kidney disease of autoimmune genesis (including acute glomerulonephritis), nephrotic syndrome.

Tuberculous meningitis, pulmonary tuberculosis.

Aspiration pneumonia (in combination with specific chemotherapy).

Berylliosis, Leffler's syndrome (not amenable to other therapy).

Multiple sclerosis.

Edema of the brain (including against the background of a brain tumor or associated with surgical intervention, radiation therapy or head trauma) after previous parenteral administration.

Prevention of graft rejection during organ transplantation.

Hypercalcemia on the background of cancer. Nausea and vomiting during cytostatic therapy.

Contraindications:

The only contraindication for short-term use for life indications is hypersensitivity to prednisolone or the components of the drug.

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

Carefully:

Caution should be given prednisolone with the following conditions and diseases:

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 periods (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.

Immunodeficiency conditions (including AIDS or HIV infection).

Diseases of the gastrointestinal tract: gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly formed intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis.

Diseases of the cardiovascular system, incl. recently suffered myocardial infarction (in patients with acute and subacute myocardial infarction it is possible to spread the focus of necrosis slowing the formation of scar tissue and as a consequence, the rupture of the heart muscle), uncompensated chronic heart failure,hypertension, hyperlipidemia.

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

Severe chronic renal and / or hepatic insufficiency, nephrourolythiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

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

Pregnancy and lactation:

During pregnancy, the use of prednisolone is possible, if the intended, benefit to the mother exceeds the potential risk to the fetus.

In the first trimester of pregnancy prednisolone applies only for vital indications.

With prolonged therapy during pregnancy, the possibility of impaired fetal growth is not ruled out. In the case of use in the III trimester of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn.

As glucocorticosteroids penetrate into breast milk, if breastfeeding is necessary during breastfeeding, breast-feeding should be discontinued.

Dosing and Administration:

The dose and duration of treatment are selected by the doctor individually, depending on the indications and severity of the disease.

Usually the daily dose is taken once or taken twice a day, in the morning, 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 prescribe at an initial dose of 20-30 mg / day, the maintenance dose is 5-10 mg / day. In some diseases (nephrotic syndrome, some rheumatic diseases), higher doses are prescribed. Treatment is stopped slowly, gradually reducing the dose. If there is a history of psychosis, high doses are prescribed under the strict supervision of a doctor.

Doses for children: the initial dose - 1-2 mg / kg / day in 4-6 receptions, supporting - 0,3-0,6 mg / kg / day.

At appointment it is necessary to consider a daily secretory rhythm of glucocorticosteroids: in the morning appoint a large (or all) part of the dose.

Side effects:

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

From the endocrine system: adrenal suppression, glucose intolerance, "steroid" diabetes or manifestation of latent diabetes mellitus, Cushing's (moon face, obesity, pituitary type, hirsutism, hypertension, dysmenorrhea, amenorrhea, myasthenia gravis, striae) syndrome, growth retardation and delay in sexual development in children.

From the gastrointestinal tract: oral candidiasis, nausea, vomiting, pancreatitis, "steroid" stomach ulcers and 12 duodenal ulcer, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the cardiovascular system: increased blood pressure, arrhythmias, bradycardia; development (in predisposed patients) or increased severity of chronic heart failure, ECG changes typical of hypokalemia, 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: hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

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

From the musculoskeletal system: slowing the growth and processes of ossification in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely - 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.

Kidney and urinary tract diseases: rapid nighttime urination, urolithiasis due to increased excretion of calcium and phosphate.

Diseases of the immune system: generalized (skin rash, skin itching, anaphylactic shock) and local allergic reactions.

Other: development or exacerbation of infections (the appearance of this side effect is promoted by jointly used immunosuppressants and vaccination), leukocyturia.

Overdose:

It is possible to increase dose-dependent side effects. It is necessary to reduce the dose of prednisolone. Treatment is symptomatic.

Interaction:

Phenobarbital, phenytoin, rifampicin, ephedrine, aminoglutethimide, aminofenazone (inducers of "hepatic" microsomal enzymes) reduce the therapeutic effect of glucocorticosteroid hormones.

It may be necessary to increase the dose of insulin and oral hypoglycemic drugs because of the weakening of hypoglycemic action.

Perhaps both strengthening and weakening of the anticoagulant effect when taking indirect anticoagulants (dose adjustment is required).

Anticoagulants and thrombolytics - increases the 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 and the development of bleeding increases (in combination with NSAIDs, a reduction in the dose of glucocorticosteroids due to the summation of the therapeutic effect) is possible in the treatment of arthritis.

Acetylsalicylic acid - prednisolone accelerates its excretion and reduces the concentration in the blood. After the abolition of glucocorticosteroid drugs, an increase in the concentration of salicylates and the development of intoxication are possible; in view of the ulcerogenic effect of salicylates, the risk of developing gastrointestinal bleeding and ulceration increases.

Indomethacin - increased risk of side effects of prednisolone (displacement of indomethacin prednisolone from bonds with albumins).

The risk of hypokalemia increases with the use of amphotericin B, diuretics, theophylline, cardiac glycosides.

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

When taking estrogens and oral estrogen-containing contraceptives, the clearance of glucocorticosteroids decreases, the half-life is prolonged, the therapeutic and toxic effects of prednisolone are intensified.

The hematoxicity of methotrexate is increasing.

Reduces the stimulating effect of somatropin on growth.

Vitamin D - its effect on calcium absorption in the intestine is reduced.

Praziquantel - its concentration decreases;

M-holinoblokatory (including antihistamines and tricyclic antidepressants) and nitrates - promotes increased intraocular pressure;

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

Adrenocorticotropic hormone enhances the effect of prednisolone.

Ergocalciferol and parathyroid hormone interfere with the development of osteopathy caused by prednisolone.

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

Glucocorticosteroids reduce the antihypertensive effect of antihypertensive drugs.

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

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

With simultaneous use with live antiviral vaccines and against other types of immunization increases the risk of virus activation and the development of infections.

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

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

Simultaneous administration of antacids reduces the absorption of prednisolone.

With simultaneous use with antithyroid drugs is reduced, and with thyroid hormones - increases the clearance of prednisolone.

Special instructions:

Before starting treatment, the patient should be examined for possible contraindications. Clinical examination should include examination of the cardiovascular system, lung X-ray examination, examination of the stomach and duodenum; system of urination, organ of vision.

Before and during the steroid therapy it is necessary to monitor the general blood test, the concentration of glucose in the blood and urine, and electrolytes in the plasma.

During the treatment with glucocorticosteroids, especially in high doses, it is not recommended to vaccinate because of a decrease in its effectiveness.

Medium and high doses of glucocorticosteroids can cause an increase in blood pressure.

With tuberculosis, the drug can only be prescribed together with anti-tuberculosis drugs.

With intercurrent infections, septic conditions, simultaneous antibiotic therapy is necessary.

With long-term treatment with glucocorticosteroids, it is necessary to prescribe potassium in order to avoid hypokalemia.

In Addison's disease, the drug should not be taken concomitantly with barbiturates because of the risk of developing acute adrenal insufficiency (addisonian crisis).

Glucocorticosteroid hormones can cause a slowdown in children and adolescents. The administration of the drug every other day usually avoids or minimizes the likelihood of such a side effect.

In the elderly, the incidence of adverse reactions increases.

In case of sudden cancellation, especially in case of high doses, there is a syndrome of "cancellation" of glucocorticosteroids: a decrease in appetite, nausea, blocking, generalized musculoskeletal pain, asthenia.

The likelihood of adrenal insufficiency as a result of taking the drug and the complications associated with it can be reduced by conducting a gradual withdrawal of the drug. After discontinuing the drug, adrenal insufficiency can last for months, so any stressful situation in this period should resume hormonal therapy.

With hypothyroidism and liver cirrhosis, the action of glucocorticosteroid hormones can be enhanced.

It is necessary to warn the patients in advance that they and their loved ones should avoid contact with patients with chicken pox, measles, herpes. In cases where systemic treatment with glucocorticosteroids or treatment with glucocorticosteroid drugs was carried out in the next 3 months, and the patient was not vaccinated, specific immunoglobulins should be prescribed.

Treatment with glucocorticosteroid drugs requires medical control in diabetes mellitus (including family history), osteoporosis (during the postmenopause risk higher), arterial hypertension, chronic psychotic reactions (glucocorticosteroid hormones can cause mental disorders and increase emotional instability), tuberculosis in the history, glaucoma, steroid myopathy, stomach ulcer and duodenal ulcer, epilepsy, simple herpes eyes (the danger of corneal perforation).

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

Patients with diabetes should monitor blood glucose and, if necessary, adjust therapy.

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

The drug may affect a person's ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, since the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

Tablets, 5 mg.

Packaging:

For 10 tablets in a planar cell package.

10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

Keep in a place protected from light and inaccessible to children, at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-001000

Date of registration:24.05.2011

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Representation: & nbspMOSHIMFARM PREPARATES them. NA Semashko OJSC MOSHIMFARM PREPARATES them.NA Semashko OJSC Russia

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Prednisolone (Prednisolon )