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(increase in the 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, 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 the effect is mainly due to inhibition of inflammatory processes,prevention or reduction of the degree of edema of the mucous membranes, a 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 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:

When administered orally prednisolone well absorbed from the gastrointestinal tract. The maximum concentration in the blood (C_max) is achieved after 1-1.5 hours after oral administration. 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. The half-life (T_1/2) after oral administration is 2-4 hours, after intravenous administration - 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, cardiogenic) - 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 the 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 conditions (including AIDS or HIV infection);

- diseases of the cardiovascular system (including recently transferred myocardial infarction - in patients with acute and subacute myocardial infarction it is possible to spread the focus of necrosis, slow the formation of scar tissue and, as a result, break the heart muscle), severe chronic heart failure, hypertension, hyperlipidemia);

- endocrine diseases - diabetes (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-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.

Prednisolone is administered intravenously (by drip or jet) or by intramuscular injection. Intravenously, the drug is usually injected first with a stream, then drip.

Adults: with acute adrenal insufficiency, a single dose of the drug is 100-200 mg, daily 300-400 mg.

In severe allergic reactions Prednisolone injected 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 the complex treatment from 75 mg 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 is administered at a dose of 500-1200 mg per day, followed by a decrease to 300 mg per day and 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. After excretion from the shock state, drip administration continues until blood pressure stabilizes. Single dose is 50-150 mg (in severe cases - up to 400 mg). Repeated drug is administered after 3-4 hours. 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 / day; in the presence of indications, the daily dose can be increased to 300-1500 mg / day and above.

With rheumatoid arthritis and systemic lupus erythematosus Prednisolone administered in addition to the system receiving the drug in doses of 75-125 mg per day is not more than 7-10 days.

With acute hepatitis Prednisolone administered at 75-100 mg / day for 7-10 days.

When poisoning with cauterizing liquids with burns of the digestive tract and upper respiratory tract Prednisolone prescribe a dose of 75-400 mg / day for 3 to 18 days.

Children from 2 to 12 months, 2-3 mg / kg of the drug are administered, from 1 to 14 years - 1-2 mg / kg of the drug intramuscularly; intravenously injected slowly (within 3 minutes). If necessary, this dose can be repeated after 20 - 30 minutes.

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: a decrease in glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus,oppression of the adrenal gland function, Itzenko-Cushing syndrome (lunar face, obesity of the pituitary type, hirsutism, increase of arterial pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delay in sexual development in children.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding and perforation of the gastrointestinal wall, increased or decreased appetite, digestive disorders, flatulence, hiccough. In rare cases - 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.

Caused by 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 is symptomatic.

Interaction:

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

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 of 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:

Solution for intravenous and intramuscular injection, 30 mg / ml.

Packaging:

1 ml per ampoule of colorless or dark glass.

For 1, 3, 5, 10 ampoules in a plastic pallet or in a blister AL / PVC, together with the instruction for use, is placed in a pack of cardboard or 3, 5, 10 ampoules, together with the instruction for use, are placed in a pack of cardboard with a cardboard separator.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014592 / 02

Date of registration:06.10.2008

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 )