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

auxiliary components: sodium hydrophosphate (anhydrous) 2.3 mg / ml, sodium dihydrogen phosphate dihydrate 0.34 mg / ml, disodium edetate 0.5 mg / ml, propylene glycol 0.25 mg / ml, water for injection up to 1 ml.

Description:

Transparent colorless or slightly yellowish solution.

Pharmacotherapeutic group:glucocorticosteroid

ATX: & nbsp

H.02.A.B.06 Prednisolone

Pharmacodynamics:

Prednisolone is a synthetic glucocorticosteroid drug, a dehydrated analog of hydrocortisone. Has anti-inflammatory, anti-allergic, anti-shock, antitoxic, immunosuppressive action, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines. It interacts with cytoplasmic receptors of glucocorticosteroids (GCS) (there are GGC receptors 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).

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

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (accumulation of fat occurs mainly in the area of the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase (increased intake of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.

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

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. Effects on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin depresses phospholipase A2, suppresses the liberation of arachidonic acid and inhibits the biosynthesis of endopersides, leukotrienes,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-lymphocyte 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 a decrease in the synthesis and secretion of mediators of allergy, inhibition of release from sensitized mast cells and basophils of histamine and other biologically active substances, a 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 adrenocorticotropic hormone (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 is bound to plasma proteins: transcortin (kortikosteroid- binding globulin) and albumin. Prednisolone metabolized in the liver, partially in the kidneys and other tissues, mainly by conjugation with glucuronic and sulfuric acids. Metabolites are inactive.

Is output through the intestine and kidney (glomerular filtration rate by 80% of the dose is reabsorbed in the renal tubules). 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, cardiogenic shock);

- with ineffectiveness of vasoconstrictors, plasma-substituting drugs and other symptomatic therapy;

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

- cerebral edema (including on the background of a brain tumor or associated with surgical intervention, radiation therapy or head trauma);

- 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.

Lactation period.

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 or latent tuberculosis. The use of the drug in severe infectious diseases is permissible only against the background of specific antimicrobial 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 mellitus (including violation of glucose tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity (III-IV item);

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

- hypoalbuminemia and conditions predisposing to its occurrence;

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

- pregnancy.

Pregnancy and lactation:

The use of the drug in pregnancy is indicated only if the expected therapeutic effect of the mother exceeds the risk of adverse effects of the drug on the fetus.

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. In 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 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. 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 failure (acute poisoning, 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 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 is administered at 75-100 mg per day for 7-10 days.

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

Children from 2 to 12 months - 2-3 mg / kg, from 1 to 14 years - 1-2 mg / kg IM; in / in is injected slowly (within 3 min).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 and severity of side effects depends on the duration of application, size of the dosage used and the possibility of compliance circadian rhythm destination.

When applying Prednisolone may be noted:

From the endocrine system: reduced glucose tolerance, "steroid" diabetes or a manifestation of latent diabetes mellitus, adrenal suppression, Cushing's syndrome (moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae) delayed 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 wall, 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 severity of chronic heart failure, ECG-changes characteristic of hypokalemia, increased blood pressure (AD), 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 central nervous system and psyche: 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 hematopoiesis: leukocytosis, thrombocytosis, a decrease in the number of eosinophils and lymphocytes.

On the part of the respiratory system, the organs of the thorax and the mediastinum: lung abscess in patients with lung cancer; increased risk of tuberculosis; myopathy, affecting the respiratory muscles.

From the urinary system: rapid nighttime urination, urolithiasis.

From the sense organs: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eyes, trophic changes in the cornea, exophthalmos.

From the side of metabolism: increased excretion of Ca²⁺, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Caused by mineralocorticoid activity - fluid retention and Na⁺ (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual 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, "steroid" acne, striae, a tendency to develop pyoderma and candidiasis.

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

Laboratory Tests: skin reactions can be suppressed during allergic tests.

Other: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

General disorders and disorders at the site of administration: sensation of "tides"; burning, numbness, tingling, pain at the injection site; infection of the injection site; necrosis of surrounding tissues, scar formation at the injection site, atrophy of the skin and subcutaneous tissue with intramuscular injection (especially when injected into the deltoid muscle).

Overdose:

It is possible to strengthen the above described side effects. It is necessary to reduce the dose of prednisolone.

Treatment: symptomatic.

Interaction:

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

Simultaneous prescription of prednisolone with:

- inducers of microsomal liver 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 potassium (K +) from the body and an increased risk of developing heart failure;

- 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 intensifies) their effect (dose adjustment is required);

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

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

- paracetamol - 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 is reduced;

- vitamin D - its effect on absorption is reduced Ca²⁺ 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 "fast" acetylators), which leads to a decrease in their plasma concentrations.

Prednisolone increases (with prolonged therapy) the content of folic acid.

Inhibitors of carbonic anhydrase, "loop ” Diuretics and Amphotericin B 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.

Joint application with cyclosporine and ketoconazole causes mutual inhibition of metabolism - the risk of side effects of both drugs (with joint use, cases of seizures were noted).

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

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

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

With simultaneous application with living antiviral vaccines and against the background of 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 caused by 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 rises.

Hypokalemia caused by SCS can increase the severity and duration of muscle blockade in the background muscle relaxants.

Special instructions:

During treatment with prednisolone (especially prolonged), it is necessary to observe the oculist, monitor blood pressure, the state of water-electrolyte balance, as well as patterns of peripheral blood and glucose concentration in the blood plasma.

In order to reduce side effects, it is possible to prescribe antacids, as well as increase the intake of potassium in the body (diet, K + preparations). Food should be rich in beams, 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 connection with an increase in the requirement for prednisolone.

In case of sudden cancellation, especially in case of prior application of high doses, it is possible to develop the "withdrawal" syndrome (anorexia, nausea, block, generalized musculoskeletal pain, general weakness), as well as an exacerbation of the disease for which it was prescribed prednisolone.

During treatment with prednisolone, vaccination should not be given 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.

Children during prolonged treatment with prednisolone should carefully monitor the dynamics of growth and development. 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 concentrations and, if necessary, adjust therapy.

An x-ray control of the osteoarticular system (images of the spine, hands) is shown.

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

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

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

During treatment, patients are advised to exercise caution when driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

Primary packaging: 1 ml of the drug in a vial of dark glass.

Secondary packaging: 3 or 10 ampoules in a plastic stand are placed in a cardboard box together with instructions for medical use.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 15 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N010299 / 01

Date of registration:13.02.2012

The owner of the registration certificate: Simpex Pharma Pvt Ltd. Simpex Pharma Pvt Ltd. India

Manufacturer: & nbsp

SIMPEX PHARMA, Pvt. Ltd. India

Representation: & nbspKORAL-MED, CJSCKORAL-MED, CJSC

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Prednisolone (Prednisolon)