Prednisolone, tablets 5 mg 100 pcs

Pharmacotherapeutic group: glucocorticosteroid.

The ATX code: N02AB06

Pharmacological properties

Pharmacodynamics

Prednisolone is a synthetic glucocorticoid drug, a dehydrated analog of hydrocortisone. It has anti-inflammatory, anti-allergic, immunosuppressive effects, increases the sensitivity of beta-adrenoreceptors to endogenous catecholamines.

It interacts with specific cytoplasmic receptors (receptors for glucocorticosteroids are in all tissues, especially in liver) with the formation of complex, inducing the formation of proteins (including enzymes regulating vital processes in cells).

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

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

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

Water-electrolyte metabolism: retains sodium and water in the body, stimulates potassium excretion (mineralocorticoid activity), reduces the absorption of calcium from the gastrointestinal tract, reduces bone mineralization.

The anti-inflammatory effect is associated with inhibition of release of inflammatory mediators by eosinophils and mast cells, induction of formation of lipocortins and reduction of the number of mast cells producing hyaluronic acid, reduction of capillary permeability, stabilization of cell membranes (especially lysosomal) and organelle membranes. Acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins at the level of arachidonic acid (lipocortin inhibits phospholipase A₂, inhibits arachidonic acid liberation and inhibits the biosynthesis of endoperoxides, leukotrienes that contribute to inflammation processes, allergies and others.), the synthesis of “pro-inflammatory cytokines” (interleukin 1, tumor necrosis factor alpha, etc.) and increases the resistance of the cell membrane to the action of various damaging factors.

The immunosuppressive effect is conditioned by involution of lymphoid tissue, suppression of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and T- and B-lymphocyte interaction, inhibition of cytokine release (interleukin-1, 2 and gamma interferon) from lymphocytes and macrophages and reduction of antibody formation.

. Antiallergic effect results from decrease of synthesis and secretion of allergy mediators, inhibition of release of histamine and other bioactive substances from sensitized mast cells and basophils, decrease of number of circulating basophils, suppression of lymphoid and connective tissue development, decrease of T- and B-lymphocytes quantity, decrease of sensitivity of effector cells to allergy mediators, suppression of antibody formation, change of immune response of the body.

In obstructive respiratory tract diseases the action is mainly caused by inhibition of inflammatory processes, prevention or reduction of mucous membrane edema, decrease of eosinophilic infiltration of submucous layer of bronchial epithelium and deposition of circulating immune complexes in bronchial mucosa, and also inhibition of erosion and mucosa desquamation. It increases sensitivity of beta-adrenoreceptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces mucus viscosity by reducing its production.

Suppresses the synthesis and secretion of adrenocorticotropic hormone and secondary to the synthesis of endogenous glucocorticosteroids.

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

Pharmacokinetics

Prednisolone is well absorbed from the gastrointestinal tract when taken orally. Maximum concentration in blood is reached 1-1.5 h after oral administration. Up to 90% of the drug is bound to plasma proteins: transcortin (cortisol-binding globulin) and albumin. Prednisolone is metabolized in liver, partially in kidneys and other tissues, mainly by conjugation with glucuronic and sulfuric acids. Metabolites are inactive.

Extracted with bile and urine by glomerular filtration and 80-90% reabsorbed by tubules. 20% of the dose is excreted unchanged by the kidneys. The plasma elimination half-life after oral administration is 2-4 hours.

Indications

• Systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis);
• acute and chronic inflammatory joint diseases: gout and psoriatic arthritis, osteoarthritis (incl.Posttraumatic), polyarthritis (including periarthritis, ankylosing spondylitis, juvenile arthritis, Still’s syndrome in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis;
• acute rheumatism, rheumatic carditis, minor chorea;
• bronchial asthma, asthmatic status;
• acute and chronic allergic diseases including.
• acute and chronic allergic diseases including allergic reactions to drugs and food products, serum sickness, urticaria, allergic rhinitis, Quincke’s edema, drug exanthema, pollinosis, etc.
• diseases of the skin: vesicles, psoriasis, eczema, atopic dermatitis (widespread neurodermitis), contact dermatitis (with involvement of a large skin surface), toxiderma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell syndrome), bullous herpetiform dermatitis, Stevens-Johnson syndrome;
• brain edema (incl.ч. against the background of a brain tumor or associated with surgery, radiation therapy, or head trauma) after prior parenteral use;
• allergic eye disease (allergic forms of conjunctivitis);
• inflammatory eye disease: sympathetic ophthalmia, severe flaccid anterior and posterior uveitis, optic neuritis;
• primary or secondary adrenal insufficiency (including.
• previous or secondary adrenal insufficiency (including condition after adrenal removal);
• congenital adrenal hyperplasia;
• renal diseases of autoimmune genesis (including acute glomerulonephritis);
• nephrotic syndrome;
• subacute thyroiditis;
• diseases of blood and hematopoietic system: agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, lymph and myeloid leukemia, lymphogranulematosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia;
• interstitial lung diseases: Acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis;
• Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy);
• lung cancer (in combination with cytostatics);
• multiple sclerosis;
• gastrointestinal diseases: ulcerative colitis, Crohn’s disease, local enteritis;
• hepatitis, hypoglycemic conditions;
• prevention of transplant rejection reaction in organ transplants;
• hypercalcemia against the background of cancer, nausea and vomiting during cytostatic therapy;
• myeloma disease.

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Active ingredient

Prednisolone

Composition

Active ingredient:

prednisolone – 0.001 g – 0.005 g

Excipients:

sucrose – 0.0300 g – 0.1500 g

potato starch – 0.0185 g – 0.0925 g

stearic acid – 0.0005 g – 0.0025 g

How to take, the dosage

The dose of the drug and the duration of treatment is determined by the physician individually, depending on the indication and the severity of the disease.

The full daily dose of the drug is recommended to be taken once or twice daily dose every other day, taking into account the circadian rhythm of endogenous glucocorticosteroid secretion between 6 and 8 a.m. The high daily dose can be divided into 2-4 doses, with a higher dose to be taken in the morning. The tablets should be taken during or immediately after a meal, washed down with a small amount of liquid.

In acute conditions and as substitution therapy, adults are prescribed an initial dose of 20-30 mg/day, with a maintenance dose of 5-10 mg/day. If necessary, the initial dose may be 15-100 mg/day, the maintenance dose is 5-15 mg/day.

In children, the initial dose is 1-2 mg/kg of body weight per day in 4-6 doses, the maintenance dose is 300-600 mcg/kg/day.

When therapeutic effect is obtained, the dose is gradually reduced – 5 mg, then 2.5 mg at 3-5 day intervals, canceling the later doses first.

If the drug is taken over a long period of time, the daily dose should be reduced gradually. Long-term therapy should not be stopped suddenly! Withdrawal of the maintenance dose is slower the longer glucocorticosteroid therapy has been used.

In case of stressful influences (infection, allergic reaction, trauma, surgery, mental overload) the dose of prednisolone should be temporarily increased (by 1.5-3 times, and in severe cases by 5-10 times) to avoid exacerbation of the underlying disease.

Interaction

In concomitant administration of prednisolone with:

– inducers of “hepatic” microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) – its concentration is reduced;

– Diuretics (especially “thiazide” and carboangiidrase inhibitors) and amphotericin B – potassium excretion increases and the risk of heart failure increases;

Sodium-containing drugs – leading to edema and high blood pressure;

– With cardiac glycosides – their tolerance decreases and the risk of ventricular extrasystole increases (because of hypokalemia);

Myorelaxants – hypokalemia caused by prednisolone can increase the severity and duration of muscle block;

– indirect anticoagulants – weakens (rarely increases) their effects (dose adjustment is required);

– anticoagulants and thrombolytics – increased risk of bleeding from gastrointestinal ulcers;

– ethanol and nonsteroidal anti-inflammatory drugs (NSAIDs) – increased risk of gastrointestinal erosive ulcers and bleeding (in combination with NSAIDs in the treatment of arthritis, the dose of glucocorticosteroids may decrease due to the summation of therapeutic effect);

Paracetamol – there is an increased risk of hepatotoxicity (induction of liver enzymes and formation of the toxic metabolite of paracetamol);

– Acetylsalicylic acid – accelerates its elimination and reduces its concentration in the blood (on cancellation of prednisolone, the level of salicylates in the blood increases and the risk of side effects increases);

– Insulin and oral hypoglycemic drugs and hypotensive medications – their effectiveness decreases;

Vitamin D – its effect on intestinal calcium absorption decreases;

Somatotropic hormone – the effectiveness of the latter decreases;

– Praziquantel – decreases the concentration of the latter;

M-cholinoblockers (including antihistamines and tricyclic antidepressants) and nitrates – increases intraocular pressure;

– Isoniazid and mexelitin – increases their metabolism (especially in “slow” acetylators), which leads to a decrease in their plasma concentrations;

– carboanhydrase inhibitors and “loop” diuretics – increases the risk of osteoporosis;

– indomethacin – displaces prednisolone from binding to albumin, increasing the risk of its side effects;

– adrenocorticotropic hormone – increases the effects of prednisolone;

– Ergocalciferol and parathormone – prevent the development of osteopathy caused by prednisolone;

– cyclosporine and ketoconazole – by slowing the metabolism of prednisolone, may in some cases increase its toxicity;

– Androgens and steroid anabolic drugs – development of peripheral edema and hirsutism, appearance of acne;

Estrogens and oral estrogen-containing contraceptives – decrease clearance of prednisolone, which may be accompanied by increased severity of its effects;

Mitotan and other inhibitors of adrenal cortex function may require increasing the dose of prednisolone;

Live antiviral vaccines and other types of immunizations increase the risk of virus activation and infection;

– antipsychotics (neuroleptics) and azathioprine – increased risk of cataracts;

– antacids – reduced absorption of prednisolone;

– antithyroid drugs – decreased, and with thyroid hormones – increased clearance of prednisolone;

– immunosuppressants – increased risk of infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus.

Prednisolone increases folic acid during long-term therapy.

Special Instructions

During treatment with the drug (especially long-term) it is necessary to monitor the ophthalmologist, control blood pressure, water-electrolyte balance, as well as peripheral blood picture and blood glucose levels.

In order to reduce side effects, antacids may be prescribed, as well as to increase the intake of potassium in the body (diet, potassium preparations). Food should be rich in proteins and vitamins, with a restriction of fat, carbohydrates and table salt.

The action of the drug is increased in patients with hypothyroidism and cirrhosis. The drug may aggravate existing emotional instability or psychotic disorders. If there is an indication of psychosis in the anamnesis, the drug in high doses is prescribed under strict medical supervision.

In stressful situations during maintenance treatment (e.g., surgery, trauma, or infectious diseases), an adjustment of the drug dose should be made due to the increased need for glucocorticosteroids.

Patients should be closely monitored for one year after completion of long-term therapy with the drug due to the possible development of relative adrenal cortical insufficiency in stressful situations.

In abrupt withdrawal, especially if high doses were previously used, withdrawal syndrome (anorexia, nausea, lethargy, generalized musculoskeletal pain, generalized weakness) and exacerbation of the disease for which the drug was prescribed may occur.

Vaccination should not be performed during treatment with the drug due to a decrease in its effectiveness (immune response).

When the drug is prescribed for intercurrent infections, septic conditions and tuberculosis, antibiotics with bactericidal action should be treated at the same time.

In children during long-term treatment with the drug it is necessary to monitor closely the dynamics of growth and development. Children who have been in contact with patients with measles or chickenpox during treatment are prescribed specific immunoglobulins prophylactically.

Because of the weak mineralocorticoid effect for replacement therapy in adrenal insufficiency the drug is used in combination with mineralocorticoids.

In diabetic patients, blood glucose levels should be monitored and therapy should be adjusted if necessary.

The radiological control of the bone and joint system (pictures of the spine, hand) is indicated.

In patients with latent infectious kidney and urinary tract diseases, the drug may cause leukocyturia, which may be of diagnostic value.

The drug increases metabolites of 11- and 17- oxytocorticosteroids.

Potential to affect reaction rate when driving or operating other mechanisms

No information available.

Synopsis

Tablets are white, flat-cylindrical, beveled, marked “R” on one side or without it.

Contraindications

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

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

With caution

Gastrointestinal diseases: Gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, nonspecific ulcerative colitis with threat of perforation or abscess, diverticulitis.

Parasitic and infectious diseases of viral, fungal or bacterial nature (current or recent, including recent contact with a patient): herpes simplex, herpes zoster (viremic phase), varicella, measles; amebiasis, strongyloidiasis; systemic mycosis; active and latent tuberculosis. Application in severe infectious diseases is allowed only against the background of specific therapy.

Pre- and postvaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination.

Diseases of the cardiovascular system, including recent myocardial infarction (patients with acute and subacute myocardial infarction may have a spread of necrosis, delay formation of scar tissue and, therefore, rupture of the heart muscle), severe chronic heart failure, arterial hypertension, hyperlipidemia.

Endocrine diseases: diabetes (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Icenko-Cushing’s disease, obesity (III-IV degree).

Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis.

Hypoalbuminemia and conditions predisposing to its occurrence.

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

Side effects

The frequency and severity of side effects depend on the duration of use, the amount of dose used, and the ability to follow the drug’s circadian rhythm.

The following side effects may occur when using the drug.

From the endocrine system: decreased glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, depression of adrenal function, Icenko-Cushing’s syndrome (moon-shaped face, pituitary obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, stretch marks), delayed sexual development in children.

In the digestive system:nausea, vomiting, pancreatitis, steroid gastric and duodenal ulcer, erosive esophagitis, gastrointestinal bleeding and perforation of the gastrointestinal wall, increased or decreased appetite, digestive disorders, flatulence, hiccups. In rare cases – increased activity of “liver” transaminases and alkaline phosphatase.

Cardiovascular system disorders:arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction – expansion of the focus of necrosis, delayed formation of scar tissue, which may lead to rupture of the heart muscle.

Nervous system disorders:Delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, cerebellar pseudotumor, headache, seizures.

From the senses: posterior subcapsular cataract, increased intraocular pressure with possible optic nerve damage, susceptibility to develop secondary bacterial, fungal or viral eye infections, trophic changes of the cornea, exophthalmus.

On the metabolic side:increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Mineralocorticoid-induced: fluid and sodium retention in the body (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

Musculoskeletal side:Stunting of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rare, pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, steroid myopathy, reduction of muscle mass (atrophy).

Skin and mucous membranes: Delayed wound healing, petechiae, ecchymosis, skin thinning, hyper- or hypopigmentation, acne, stretch marks, tendency to develop pyoderma and candidiasis.

Allergic reactions:skin rash, itching, anaphylactic shock.

Others:the development or exacerbation of infections (the appearance of this side effect is promoted by co-administration of immunosuppressants and vaccination), leukocyturia, “withdrawal” syndrome.

Overdose

Symptoms: the side effects described above may worsen. It is necessary to reduce the dose of the drug. Treatment: symptomatic.

Pregnancy use

During pregnancy (especially in the first trimester) it is used only for vital indications. Prolonged therapy during pregnancy may impair fetal growth. When used in the third trimester of pregnancy, there is a risk of adrenal cortex atrophy in the fetus, which may require substitution therapy in the newborn. Since glucocorticosteroids pass into the breast milk, it is recommended to stop breastfeeding if it is necessary to use the drug during breastfeeding.

Similarities

Prednisol, Prednisolone