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

Prednisolone is a synthetic glucocorticoid drug, a dehydrated analog of hydrocortisone. Has anti-inflammatory, antiallergic, immunosuppressive, 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.)

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 oppresses phospholipase A2,suppresses 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 the 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 Na+ and water in the body, stimulates the excretion of K + (mineralocorticoid activity), reduces the absorption of Ca²⁺ from the gastrointestinal tract, causes "washing away" of calcium from the bones and increasing 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.

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

Pharmacokinetics:

Up to 90% of 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. Half-life from the plasma after intravenous administration is 2-3 hours.

Indications:

Prednisolone is used for emergency therapy in conditions requiring a rapid increase in the concentration of glucocorticosteroids in the body:

- shock conditions (burn, traumatic, operational, toxic) - with ineffectiveness of vasoconstrictors, plasma-substituting drugs and other symptomatic therapy;

- allergic reaction (acute severe), transfusion shock, anaphylactic shock, anaphylactoid reactions;

- brain edema (including on the background of a brain tumor or associated with surgery, radiation therapy, or head injury);

- bronchial asthma (severe form), asthmatic status;

- systemic connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis);

- acute adrenal insufficiency;

- thyrotoxic crisis;

- acute hepatitis, hepatic coma;

- Reduction of inflammatory phenomena and prevention of cicatricial narrowing (with poisoning by cauterizing fluids).

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:

With caution, the drug should be administered in the following conditions 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 (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);

· diseases of the cardiovascular system, incl. recent myocardial infarction (in patients with acute and subacute myocardial infarction, the spread of the necrosis foci, slowing the formation of scar tissue and, as a result, the rupture of the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia;

· endocrine diseases - diabetes (including violation of tolerance to carbohydrates), hyperthyroidism, hypothyroidism, 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.

Pregnancy and lactation:

At pregnancy (especially in 1 trimester) apply only on 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. Prednisolone injected intravenously (by drip or jet) or by intramuscular injection. Intravenously, the drug is usually injected first with a stream, then drip.

In acute adrenal insufficiency single dose of the drug is 100 - 200 mg, daily 300-400 mg.

In severe allergic reactions Prednisolone is administered in a daily dose of 100-200 mg for 3-16 days.

With bronchial asthma the drug is administered depending on the severity of the disease and the effectiveness of complex treatment from 75 to 675 mg for a course of treatment from 3 to 16 days; in severe cases, the dose may be increased to 1,400 mg per treatment course and more with a gradual dose reduction.

With asthmatic status Prednisolone injected at a dose of 500-1200 mg per day, followed by a decrease to 300 mg per day and the transition to maintenance doses.

With thyrotoxic crisis Introduce 100 mg of the drug in a daily dose of 200-300 mg; if necessary, the daily dose can be increased to 1000 mg. The duration of administration depends on the therapeutic effect, usually up to 6 days.

In shock, resistant to standard therapy, Prednisolone At the beginning of therapy, injections are usually given, after which they pass to a drip introduction. If the arterial pressure does not increase within 10-20 minutes, repeat the fluid administration of the drug. Single dose is 50-150 mg (in severe cases - up to 400 mg). Repeated drug is administered after 3-4 hours. After excretion from the shock state, drip administration continues until blood pressure stabilizes. The daily dose can be 300-1200 mg (with a subsequent dose reduction).

In acute hepatic-renal insufficiency (for acute poisoning, in the postoperative and postpartum periods, etc.) Prednisolone administered at 25-75 mg per day; in the presence of indications, the daily dose can be increased to 300-1500 mg per day or more.

With rheumatoid arthritis and systemic lupus erythematosus Prednisolone is administered in addition to the systemic administration of the drug at a dose of 75-125 mg per day for not more than 7-10 days.

With acute hepatitis Prednisolone Enter 75-100 mg per day for 7-10 days.When etching with cauterizing liquids with burns of the digestive tract and upper respiratory tract Prednisolone prescribe a dose of 75-400 mg per day for 3-18 days.

If intravenous injection is not possible, Prednisolone administered intramuscularly in the same doses. After relief of acute condition is prescribed inside Prednisolone in tablets, followed by a gradual decrease in the dose. 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: 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, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccough. 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 manifestation of 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, cerebellar pseudotumor, headache, convulsions.

From the sense organs: sudden loss of vision (with parenteral administration in the head, neck,turbinate, the scalp may be deposited drug crystals in the blood vessels of the eye), posterior subcapsular cataracts, increased intraocular pressure with possible damage to the optic nerve, the propensity to develop secondary bacterial, fungal or viral infections of the eyes, corneal trophic 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 retention and sodium (peripheral edema), hypernatremia, signs of hypokalemia (arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

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

From the skin and mucous membranes: Delayed wound healing, petechiae, ecchymoses, skin thinning, hyper- or hypopigmentation, acne, striae, propensity to develop pyoderma and candidiasis.

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

Local: 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 the / m introduction (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.

With IV introduction: arrhythmias, "tides" of blood to the face, seizures.

Overdose:

It is possible to strengthen the above described side effects.

It is necessary to reduce the dose of Prednisolone.

Treatment symptomatic.

Interaction:

Possible pharmaceutical incompatibility of Prednisolone with other intravenously administered drugs - it is recommended to administer it separately from other drugs (iv bolus,dropper as a second solution). When mixing the solution of prednisolone with heparin a precipitate forms.

Simultaneous prescription of Prednisolone from:

· inducers of "hepatic" microsomal enzymes (phenobarbital, phenytoin, theophylline, rifampicin, 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 the body;

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

· amphotericin B increased risk of heart failure;

· cardiac glycosides their tolerability worsens and the likelihood of developing ventricular extrasystole increases (due to induced hypokalemia);

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

· anticoagulants and fibrinolytics increased risk of bleeding from ulcers in the gastrointestinal tract.

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

· paracetamol increased risk of hepatotoxicity (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 - reduces its effect on absorption Ca²⁺ in the intestine;

· somatotropic hormone It 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.

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.

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 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 withlower 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.

Antipsychotics (antipsychotics) and azathioprine increase the risk of developing cataract in the appointment of prednisolone.

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

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 pictures of peripheral blood and blood glucose level.

In order to reduce side effects, it is necessary to 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), it is necessary to adjust the dose of the drug in response to the increased need e glucocorticosteroids. In case of sudden cancellation, especially in case of prior application of high doses, the development of the "withdrawal" syndrome (anorexia, nausea, inhibition, generalized musculo-skeletal pain, general weakness) is possible. a also an exacerbation of the disease, about which was appointed Prednisolone.

During treatment Prednisolone should not be vaccinated due to a decrease in its effectiveness (immune response).

Assigning Prednisolone with intercurrent infections, septic states tuberculosis, it is necessary to simultaneously carry out 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.

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

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

Form release / dosage:

Solution for injection, 15 mg / ml.

Packaging:

In ampoules of 2 ml.

Packaging: for 3 or 5 ampoules in a contiguous cell package.

1 a 3 or 5 ampoule contour pack with the instruction for use is placed in a cardboard box.

2 or 20 contour cell packs of 5 ampoules, along with the instructions for use are placed in a cardboard box.

Storage conditions:

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

Shelf life:

3 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:P N002692 / 01

Date of registration:17.06.2008

The owner of the registration certificate:RUSSIAN CARDIOLOGICAL NPK FGU ROSMEDTEKHNOLOGIY - EXPERIMENTAL PRODUCTION OF MEDICAL AND BIOLOGICAL PREPARATIONS RUSSIAN CARDIOLOGICAL NPK FGU ROSMEDTEKHNOLOGIY - EXPERIMENTAL PRODUCTION OF MEDICAL AND BIOLOGICAL PREPARATIONS Russia

Manufacturer: & nbsp

RUSSIAN CARDIOLOGICAL NPK FGU ROSMEDTEKHNOLOGIY - EXPERIMENTAL PRODUCTION OF MEDICAL AND BIOLOGICAL PREPARATIONS Russia

Information update date: & nbsp29.08.2015

Illustrated instructions

Instructions

Prednisolone (Prednisolon )