Project Description

Prednisolon

(tablets 0,005 g) Tabuletae Prednisoloni 0,005

international nonproprietary name

Prednisolon.

Ref

BP-0112

Pharmacotherapeutic group

Corticosteroids for systemic administration. Glucocorticoids.

Composition of the preparation

1 tablets contains prednisolon 5 mg.

Pharmacological action

Pharmacodynamics

The preparation is a synthetic analogue of the hormones released by the adrenal cortex. It has an anti-inflammation, antiallergic, immunosuppressive and antishock action. It increases the production of lipocortins inhibiting phospholipase A2, and reduces the synthesis of arachidonic acid metabolism products — cyclic endoperoxides, prostaglandins, thromboxane. It stabilizes lysosome membranes, inhibits hyaluronidase synthesis, decreases the production of lymphoquins and inhibits macrophage migration. Antiallergic affect is conditioned by the reduction in number of basocytes, direct inhibition of secretion and synthesis of immediate allergy mediators. It induces lymphopenia and lymphoid tissue involution that leads to immunosuppression. It has an antishock action, Intensifies the action of catecholamine and restores receptor sensitivity to catecholamines. It reduces the amount of protein in plasma, intensifies protein catabolism in muscle tissue, increases its synthesis in the liver. It provides the development of higher fatty acids and triglycerines, as well as the redistribution of fat. It increases the resorption of carbohydrates from the gastrointestinal tract, the activity of glucose-6-phosphase and оphosphoenolpyruvatchinase that lead to the mobilization of glucose into blood flow and the intensification of glucogenesis. It holds sodium and water and contributes to calcium excretion due to mineralcorticoid action. It decreases the absorption of calcium in the intestine, increases its washing out of bones and kidney excretion. It suppresses fibroblast activity and creation of collagen.

Pharmacokinetics

On oral administration it is well absorbed from the gastrointestinal tract. Max.concentration in plasma is reached 60-90 minutes after the administration. 90% prednisolon in plasma is bound (with transcortin and albumin). It penetrates through placenta barrier and small quantities of the preparation are found in breast milk. It is subject to biotransformation mainly in the liver by oxidation; oxygenized forms are glucuronized or sulphanized. Biotransformation takes place even in the kidney, small intestine, bronchi. The half-period is 2-4 hours. It is excreted by the kidney, 20% unaltered.

Indications 

Acute rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, systemic angiitis, systemic acleroderma, Bekhterev’s disease, chorea minor, acute adrenal cortex failure, adrenogenital syndrome; non specific ulcerative colitis, Crohn’s disease, hepatitis, hepatic coma; glomerulonephritis, lipoid nephrosis; agranulocytosis, different forms of leucosis, lymphogranulomatosis, thrombocytopenic pupura, hemolytic anemia, prophylaxis of graft rejection reaction; bronchial asthma; acute and chronic allergic diseases, pemphigus, eczema, itching, exfoliative dermatitis, psoriasis, pruritus, eczema, seborrheic dermatitis, erythroderma, psoriasis, alopecia; allergic, chronic and atypical conjunctivitis and blepharitis; retina inflammation on undamaged mucous; acute and chronic inflammation of the front section of vascular membrane, sclera and episclera; sympathetic ophthalmia.

special indication

Not established

special warning

Not established

Dosage and method of administration

Tablets of prednisolon are for oral administration. The dose is determined individually.On prescription of the preparation the daily secretory rhythm of glucosteroids should be taken into account: the bigger amount of (or the whole) dose is administered in the morning.Treatment should be ceased step-by-step reducing the dose.

On oral administration as an replacement therapy the initial dose for adults shall be 20-30 mg/day (4-6 tablets), the maintaining dose 5-10 mg/day (1-2 tablets). If necessary, the initial dose should be 15-100 mg/day (3-20 tablets), maintaining – 5-15 mg/day (1-3 tablets). The daily dose should be reduced gradually. For children the initial dose is 1-2 mg/kg/day for 4-6 intakes, the maintaining dose is 0,3-0,6 mg/kg/day.

The highest daily dose in adults is 0,1 g.

Treatment with prednisolon should be carried out on occurrence of clear symptoms and under doctor’s control.

After termination of treatment withdrawal syndrome, kidney failure and exacerbation of the disease, in relation to which prednisolon was prescribed, are possible.

Pregnancy and lactation: in case of pregnancy (esp.in I trimester) the preparation is administered only if it is necessary to support the patient’s life. If necessary to use in the lactation period, it is recommended to consider thoroughly the expected benefit of the treatment for the mother and risk for the child.

The preparation does not affect the ability to drive and work with the machines.

overdosage

Not established

safety measures

Treatment (esp.prolonged one) should be carried out under the oculist’s control, monitoring of blood pressure and water and electrolytic balance should be made, as well as the assay of peripheral blood and glucose in blood. To decrease side effects the dose of calcium should be increased (diet, calcium preparations).

The preparation should be taken with care in patients with indication of psychosis in the anamnesis, with non specific infections accompanied by chemotherapy and antibiotic treatment.

On diabetes the administration of the preparation is possible only on the absolute assay or for prophylaxis of expected resistance to insulin. In case of latent form of tuberculosis prednisolon may be used in combination with antituberculosis medications. In case of Addison’s disease the preparation cannot be used with barbiturates simultaneously.

Side effects

The frequency of development and evidence of side effects depend on the duration of administration and the amount of the dose.

Endocrine system:Cushing’s syndrome, increase in body weight, hyperglycemia up to steroid diabetes development, emaciation (up to atrophy) of the adrenal cortex function, sexual development delay in children.

Digestive system:nausea, vomiting, higher gastric acidity, ulcerogenic action, limosis or loss of appetite, meteorism, singulation.

Metabolism:higher calcium excretion, sodium retention in the organism with edema, negative nitrogen balance.

Cardiovascular system:arterial hypertension, arrhythmia, bradycardia.

Coagulating blood system:increased coagulability.

Musculoskeletal system: “steroid” myopathy, muscle mass reduction, osteoporosis, avascular necrosis, growth impairment, ossification processes.

Skin integument and mucous membrane:slow wound healing, petechia, ecchymoma, thinning, hyper- and hypopigmentation, acne, stretch marks, disposition to pyoderma and candidosis development.

Visual organ:steroid cataract, latent glaucoma induction.

Nervous system:mental disorders.

Allergic reactions:common (rush, itching, anaphylactic shock), local allergy reactions.

Others:decrease of resistance to infections, withdrawal syndrome.

Contraindications

Hypersensitivity, stomach and duodenum peptic ulcer in an acute form, decompensated diabetes, severe arterial hypertension, osteoporosis, Cusing’s syndrome, vaccination period, tuberculosis active form, glaucoma, systemic mycosis, acute viral infection, productive symptomatology on psychic diseases, viral and bacterial eye diseases, primary glaucoma, cornea disease with epithelium damage, bacterial, fungoid and viral skin damages, tuberculosis, syphilis, skin swelling.

Interactions with other medicinal preparations

Prednisolon intensifies toxicity of cardiac glycoside (due to developing hypokalemia the risk of arrhythmia is high). It intensifies the excretion of acetylsalicylic acid, reduces its concentration in blood (in case of prednisolon withdrawal the salicylates concentration in blood increases and side effects develop). When live-virus vaccines are administered and on the basis of other types of immunization, the preparation increases the risk of virus activation and development of infections. It intensifies the metabolism of isoniazide and mexiletine that leads to the reduction of their concentration in plasma. It also increases the risk of hepatoxic reaction of paracetamol (due to induction of “liver’ enzymes and formation of toxic paracetamol metabolite). It increases (on prolonged therapy) the content of folic acid. Hypokaliemia caused by the administration of prednisolon may increase the intensity and duration of muscular blockade on the basis of administration of miorelaxants. High doses of the preparation reduce the action of somatropin. It reduces the action of hypoglycemic preparations, increases anticoagulant action of coumarine derivatives. It weaken the action of vitamin D onto the calcium absorption in the intestine lumina. It reduces the concentration of praziquantel in blood.

Antacids reduce the absorption of prednisolon. Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase its toxicity. Thiazide diuretics, carbohydraze inhibitors and other glucosteroids and amphotericin амфотерицин В increase the risk of hypokaliemia development, Na+-containing preparations increase the risk of edema and high blood pressure. Non steroid anti-inflammation preparations and ethanol increase the risk of mucosal ulceration of gastrointestinal mucous membrane and blood flow. In combination of prednisolon with non steroid anti-inflammation preparations the summation of anti-inflammation effect is observed. Indometacin that displaces prednisolon from the bond with albumin, increases the risk of side effects development. Amphotericin В and carbohydrase inhibitors increase the risk of osteoporosis development. Therapeutic action of prednisolon is reduced by phenytoin, barbiturates, ephedrine, theophyllin, rifampicin and other inductors of “liver” microsomal enzymes (increasing of the metabolism speed). Mitothan and other inhibitors of adrenal cortex may condition the advisability of a higher prednisolon dose. Clearance of prednisolon increases on the basis of administration of thyroid hormones. Immunosuppressants increase the risk of infection development. Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of prednisolon, prolong the half-period and intensify therapeutic and toxic effects. Cases of pilosis and acne on administration of prednisolon are caused by simultaneous administration of other steroid hormone preparations – androgen, extragen, anabolics, oral contraceptives. Tricyclic antidepressants increase the depression intensity induced by administration of prednisolon. The risk of cataract development is higher when prednosolon is used with neuroleptics, carbutamides and azathioprine. Simultaneous administration with М-choline-blockers (comprising antihistamine preparations, tricyclic antidepressants), nitrates induces higher intraocular pressure.

The form of release

5 mg tablets. 10 tablets in a blister. 5 blisters in a package.