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

Excipients: sodium hydrogen phosphate (disodium phosphate anhydrous, sodium dihydrogen phosphate) 2.3 mg, sodium dihydrogen phosphate dihydrate 0.34 mg, propylene glycol 150.0 mg, disodium edetate dihydrate (disodium ethylenediamine-N, N , N ', N'-tetraacetic acid 2-aqueous [Trilon B]) - 0.5 mg, water for injection - up to 1 ml.

Description:Transparent, colorless or slightly yellowish liquid.

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, antiallergic, immunosuppressive, anti-shock effect, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

Interacts with the cytoplasmic receptors of glucocorticosteroids (GCS) to form a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells).

Anti-inflammatory action 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 capillary permeability, stabilization of cell membranes and membranes of organelles (especially lysosomal ones). Acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin depressesphospholipase A2, inhibits the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, promoting inflammation processes, allergies, etc.); synthesis of "pro-inflammatory cytokines" (interleukin-1, tumor necrosis factor alpha, etc.); increases the resistance of cell membranes to the action of various damaging factors.

Immunosuppressive action 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 and interleukin-2, gamma-interferon) from lymphocytes and macrophages and a decrease in 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 swelling of bronchial 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 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.

Influence on protein metabolism: reduces the number of globulins in the blood 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.

Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (mobilization from the subcutaneous tissue of the extremities and accumulation of fat mainly in the region of the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Influence on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract (GIT); increases the activity of glucose-6-phosphotase (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.

Influence on water-electrolyte exchange: Delay sodium and water in the body, stimulate the excretion of potassium (mineralocorticoid activity) reduces the absorption of calcium from the intestine, causing "washout" of calcium from bones and increase its renal excretion, reduces bone mineralization.

Pharmacokinetics:

Absorption

Absorption when injected into the muscles of the thigh is faster than when injected into the gluteal muscles. When administered intravenously, the maximum plasma concentration is reached after 0.5 hours. With intramuscular administration the maximum concentration is reached after 0.5-1 hours.

Distribution

Up to 90% of prednisolone binds to plasma proteins: transcortin (corticosteroid-binding globulin) and albumins.

Metabolism

Prednisolone is metabolized predominantly in the liver, partially in the kidneys and other tissues, mainly by conjugation with glucuronic and sulfuric acids. Metabolites are inactive.

Excretion

The half-life of prednisolone from the blood plasma is about 3 hours.

It is excreted through the intestine and kidneys by glomerular filtration and is 80-90% reabsorbed by the renal tubules. 20% of the dose is excreted by the kidneys unchanged.

Indications:

The drug is used for emergency therapy in conditions requiring a rapid increase in the concentration of GCS in the body:

- Shock (burn, traumatic, operational, toxic, anaphylactic, hemotransfusion) - with ineffectiveness of vasoconstrictors, plasma-substituting drugs and other symptomatic therapy.

- Allergic reactions (acute and severe forms), anaphylactoid reactions, serum sickness.

- Bronchial asthma (severe form), asthmatic status.

- Cerebral edema (only after confirming the symptoms of increased intracranial pressure by the results of magnetic resonance or computed tomography),caused by a brain tumor and / or associated with surgery or radiotherapy.

- Systemic diseases of connective tissue: rheumatoid arthritis, systemic lupus erythematosus.

- Acute hepatitis, hepatic coma.

- Primary and secondary adrenal insufficiency (in combination with mineralocorticosteroids if necessary, especially in children).

- Acute adrenal insufficiency (if necessary in combination with mineralocorticosteroids).

- Thyrotoxic crisis.

- Others: the need to reduce inflammatory phenomena and prevent cicatricial narrowing (when poisoning with cauterizing fluids).

Contraindications:

For short-term use according to vital indications, the only contraindication is hypersensitivity to prednisolone or components preparation.

Systemic fungal infections.

Epidural and intrathecal administration of the drug.

Cerebral edema due to head injury.

Simultaneous use of live or diluted vaccines with immunosuppressive doses of the drug Prednisolone.

Eye infection caused by the herpes simplex virus (due to the risk of corneal perforation).

The use of the drug is not recommended in patients with acute or subacute myocardial infarction, since a necrosis foci may spread, a delay in the formation of scar tissue and, as a consequence, a rupture of the heart muscle.

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

Breastfeeding period.

Carefully:

- In 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.

- With 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, stenpyloidosis; active or latent tuberculosis. Application in severe infectious diseases is permissible only against the background of specific antimicrobial therapy.

- During the pre-and post-vaccination period (8 weeks before and 2 weeks after vaccination), with lymphadenitis after BCG vaccination. With immunodeficiency states (incl.AIDS or HIV infection).

- In diseases of the cardiovascular system: recent myocardial infarction, chronic heart failure in the stage of decompensation, hypertension, hyperlipidemia.

- With endocrine diseases: diabetes mellitus (including violation of glucose tolerance), hyperthyroidism, hypothyroidism, obesity (III-IV st).

- In chronic renal and / or hepatic insufficiency, severe nephrourolythiasis. With hypoalbuminemia and conditions predisposing to its occurrence (cirrhosis, nephrotic syndrome).

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

- In patients with thromboembolic complications now or having a predisposition to the development of these complications.

- In severe affective disorders.

- With convulsive syndrome.

- During pregnancy.

In elderly patients, the drug should be used with caution in connection with the increased risk of osteoporosis and hypertension.

In children during growth prednisolone It should be used only under absolute indications and under very careful supervision of the attending physician.

Pregnancy and lactation:

Prednisolone penetrates the placenta. During pregnancy (especially in the first trimester) or in women planning pregnancy, the use of the drug is indicated only if the expected therapeutic effect of the drug exceeds the risk of negative effects on the mother or fetus. SCS should be administered during pregnancy only on absolute indications. With prolonged therapy during pregnancy, malformations (cleft palate) and fetal hypotrophy are possible. Information on the effect of GCS on the course and outcome of labor is absent. Careful observation of children born to mothers who received sufficiently high doses of the drug during pregnancy is necessary.

Since GCS penetrates into breast milk, if necessary, the use of the drug Prednisolone from breastfeeding the child should be discarded.

Dosing and Administration:

Intravenous (drip or jet), intramuscularly.

Intravenously, the drug is usually injected first with a stream, then drip.

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.

In acute adrenal insufficiency the drug is administered in the initial single dose from 90-120 mg to 180 mg, the daily dose is 300-390 mg.

In severe allergic reactions the drug is administered in a daily dose of 90-120 mg to 180 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 60-90 mg to 660 mg for a course of treatment from 3 to 16 days; in severe cases, the dose may be increased to 1380 mg per course of treatment and more with a gradual dose reduction.

With asthmatic status the drug is administered at a dose of 510-1200 mg per day, followed by a decrease to 300 mg per day and transition to maintenance doses.

With thyrotoxic crisis the recommended initial dose of the drug is 90-120 mg; daily dose - up to 300 mg. If necessary, the daily dose can be increased to 900 mg. The duration of administration depends on the therapeutic effect, usually up to 6 days. In shock, resistant to standard therapy, the drug at the beginning of therapy is usually injected in a jet, after which they switch to a drop 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. The initial single dose is 60-150 mg, in severe cases - up to 390 mg. Repeated drug is administered after 3-4 hours. The daily dose can be 300 to 1200 mg, followed by a lower dose.

In acute hepatic-renal insufficiency (for acute poisoning, in the postoperative and postpartum periods, etc.), the drug is administered at 30-90 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 the drug is administered in addition to the systemic administration of the drug in a dose of 60-120 mg per day for no more than 7 to 0 days.

With acute hepatitis the drug is administered at 60-120 mg per day for 7-10 days.

When poisoning with cauterizing liquids with burns of the digestive tract and upper respiratory tract the drug is prescribed in a dose of 60-390 mg per day for 3 to 18 days.

Single dose for children: children from 2 to 12 months are administered at the rate of 2-3 mg / kg body weight; 1-14 years - 1-2 mg / kg intravenously, jet or deep intramuscularly.The solution should be administered intravenously slowly (about 3 minutes). If necessary, repeat the introduction of the drug after 20-30 minutes.

If intravenous injection is not possible, the drug is 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 depend on the duration of application, the amount of dose used and the possibility of observing the circadian rhythm of prescribing the drug.

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 of 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, increase or decrease in appetite, digestive disorders, flatulence, hiccups. In rare cases - increased activity of "liver" transaminases and alkaline phosphatase.

From the side of the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of heart failure, changes in the electrocardiogram, characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

From the nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the sense organs: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral eye infections, trophic corneal changes, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal concha, 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 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: skin rash, itching, anaphylactic shock, local allergic reactions.

Local Reactions: burning, numbness, pain, tingling at the injection site, infection 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:Symptoms: it is possible to enhance the dose-dependent side effects described above.

Treatment: symptomatic therapy. It is necessary to reduce the dose of the drug.

Interaction:

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

When mixing a solution of prednisolone with heparin a precipitate is formed.

Prednisone with prolonged therapy can increase the content folic acid.

The simultaneous use of prednisolone with:

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

- diuretics (special "thiazide" and inhibitors of carbonic anhydrase) and amphotericin B can lead to increased excretion from the body of potassium and an increased risk of developing heart failure;

- sodium-containing preparations can lead 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 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-ulcerative lesions of the gastrointestinal tract and development of bleeding increases (in combination with NSAIDs in the treatment of arthritis, there may be a reduction in the dose of GCS 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 elimination and reduces the concentration in the blood (with the abolition of prednisolone, the concentration 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 - decreases its effect on calcium absorption in the intestine;

- somatotropic hormone - reduces its effectiveness, and with praziquantel - its concentration in the blood;

- m-holinoblokatorami (including antihistamines and tricyclic antidepressants) and nitrates - promotes increased intraocular pressure;

- tricyclic antidepressants - may increase the severity of depression caused by taking GCS (not shown for the therapy of these side effects);

- 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 application 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.

With simultaneous application from living antiviral vaccines and against the background other types of immunization 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.

Simultaneous application 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.

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

Immunosuppressive drugs increase the risk of infection and lymphoma or other lymphoproliferative disorders caused by the Epstein-Barr virus.

Simultaneous use of prednisolone with sultopride increases the risk of arrhythmia.

Simultaneous use of prednisolone with antihypertensive drugs can cause a decrease in the hypotensive effect due to the delay of sodium and water.

Simultaneous use of prednisolone with fluoroquinolones increases the risk of tendonitis, in rare cases can lead to rupture of tendons.

Special instructions:

In view of the risk of arrhythmia, the use of the drug in high doses should be carried out in a hospital equipped with the necessary equipment (electrocardiograph, defibrillator).

If prolonged spontaneous remission develops, treatment should be discontinued.

During the treatment with the drug, the patient should undergo a regular examination (weight control, chest radiography and abdominal cavity, and if possible, endoscopic examination of the gastrointestinal tract (if there is a history of gastric ulcerative lesions)).

During treatment with the drug Prednisolone (especially long) it is necessary to observe the oculist, control blood pressure, the state of water-electrolyte balance, as well as patterns of peripheral blood and blood glucose concentration.

In order to reduce the side effects for the period of treatment with high doses of the drug The intake of potassium and calcium in the body (intake of food rich in potassium and calcium, or intake of potassium, calcium and vitamin D) should be increased. 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.

Against the background of high doses of prednisolone, there is a risk of acute pancreatitis.

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), a correction of the dose of the drug should be made in response to an increase in the need for GCS. Temporary increase in the dose of the drug in stressful situations is necessary both before and after stress.

Long-term use of high doses of the drug requires a gradual dose reduction in order to prevent acute adrenocortical insufficiency. With a sharp withdrawal of the drug there is a risk of developing acute adrenal insufficiency up to a lethal outcome.

With the sudden cancellation, particularly in the case of the prior use of high doses may develop the syndrome '' cancel '(anorexia, nausea, lethargy, generalized musculoskeletal pain, fatigue), as well as worsening of the disease, about which he was appointed Prednisolone.

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

When prescribing the drug for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously carry out specific antimicrobial therapy.

At children during long treatment by a preparation careful monitoring over 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 mineralocorticosteroids.

In patients with diabetes mellitus, the concentration of blood glucose should be monitored and, if necessary, corrected by 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 significance.

The use of prednisolone in patients with Isenko-Cushing's disease should be avoided in view of the possible intensification of clinical manifestations.

Prednisolone may increase susceptibility to infectious diseases, a more severe course (possibly fatal if chicken pox, measles and other infections in unimmunized patients) or mask their symptoms.

Taking the drug may mask the symptoms of "irritation of the peritoneum" in patients with perforation of the wall of the stomach or intestine.

In connection with the registration of cases of thrombosis, including venous thromboembolism, against the background of GKS therapy, it is necessary to observe precautions in patients with thromboembolic complications currently or having a predisposition to the development of these complications.

May worsen myasthenia flow.

SCS can negatively affect fertility.

Against the background of the use of GCS, a change in the mobility and the number of spermatozoa is possible. Prednisolone increases the content of metabolites of 11- and 17-oxyketocorticosteroids.

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

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

Form release / dosage:

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

Packaging:

1 ml of the drug in the ampoules of light-protective glass.

10 ampoules are placed in a box of cardboard.

3, 5, 10 ampoules are placed in a contour cell pack of film nolivinyl chloride and aluminum foil printed lacquered, or without foil.

1 a 3-ampoule contoured cell pack is placed in a pack of cardboard.

1, 2, 5, 10 contour cells with 5 or 10 ampoules are placed in a pack of cardboard.

In each pack, the box is attached instructions for use, the ampullar scarifier.

Ampoule scapper does not invest in case of using ampoules with a kink ring or with an incision and a point.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003832

Date of registration:14.09.2016

Expiration Date:14.09.2021

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp29.09.2016

Illustrated instructions

Instructions

Prednisolone (Prednisolon)