Ekoral capsules 25mg, No. 50

• the need to suppress immunity after transplantation of kidneys, bone marrow, solid organs;

• rheumatoid arthritis with a high degree of activity with resistance to basic therapy;

• severe forms of psoriasis and atopic dermatitis with the ineffectiveness of standard therapy;

• nephrotic syndrome caused by the pathology of the vascular glomerulus (nephropathy of minimal changes, focal and segmental glomerulosclerosis, membranous glomerulonephritis).

Transplantation

For adults, as a rule, cyclosporine is prescribed together with other immunosuppressive drugs. The initial dose is 10-14 mg / kg / day in 2 doses with an interval of 12 hours for 1-2 weeks after surgery. Then, the concentration of cyclosporine in the blood plasma is monitored and the dose is gradually reduced to 2-6 mg / kg / day, also in 2 divided doses. The therapeutic range of plasma cyclosporine concentrations for subsequent administration is 100 to 400 ng / ml. With kidney transplantation, when using cyclosporine in doses less than 3-4 mg / kg and with a concentration of cyclosporine in the blood plasma of about 100 ng / ml, there is a risk of developing rejection reactions. For some patients, a month after transplantation, while taking GCS, a dose of less than 5 mg / kg is recommended.

In bone marrow transplantation, short-term use of cyclosporine in combination with methotrexate is usually recommended. The dose of cyclosporin is selected individually (1-2 days before the operation, intravenous administration of cyclosporine at a dose of 2.5-5 mg / kg / day is recommended). After the operation, as soon as it becomes possible to take the drug inside, they switch to a dose of 12.5 mg / kg / day (in 2 doses) for 3-6 months. Further, the dose is gradually reduced until the complete end of the course of treatment. When treating an acute graft versus host reaction, the initial dose of cyclosporine is 12.5-15 mg / kg / day in 2 divided doses. After 50 days, the dose is started to be reduced each time by 5% for a week and the therapy is discontinued after about 20 weeks. If, after discontinuation of cyclosporine, an acute reaction develops again, therapy should be repeated.If transient gastrointestinal complaints are observed when taking cyclosporine for organ transplantation, bone marrow transplantation and in acute graft-versus-host reactions, 1/3 of the recommended daily dose can be administered once intravenously (in the appropriate dosage form). The duration of the use of cyclosporine in organ transplantation (with the exception of acute graft-versus-host therapy) is determined individually.) is set individually.) is set individually.

Other diseases

In severe endogenous uveitis, the initial dose of cyclosporine is 5-10 mg / kg / day in 2 divided doses until inflammation decreases and visual acuity improves. In acute cases, you can additionally prescribe prednisolone at a dose of 200-600 mcg / kg / day or another similar corticosteroids. During maintenance therapy, the dose should be reduced gradually until the minimum effective dose is reached. The therapeutic level of the concentration of cyclosporine in the blood is between 100 and 150 ng / ml. The duration of use is from 3 to 16 months.

In severe forms of psoriasis, the drug is recommended to be prescribed at a dose of 2.5 mg / kg / day in 2 divided doses. If after 1 month of therapy there is no improvement in the condition of the skin, you can gradually increase the dose by 1 mg / kg, up to a maximum of 5 mg / kg / day in 2 divided doses. When repeated treatment, cycloporin should be used in the minimum effective dose. If, when using cyclosporine at a dose of 5 mg / kg / day after 6 weeks, there is no significant improvement, then the drug should be discontinued. The duration of use is usually 12 weeks. In case of nephrotic syndrome, subject to normal renal function, adults are recommended to prescribe the drug in a daily dose of no more than 5 mg / kg, for children - no more than 6 mg / kg, in 2 divided doses.

For patients with impaired renal function, the initial dose of cyclosporine should not exceed 2.5 mg / kg. When the serum creatinine level in adults is more than 200 ?mol / l and in children - more than 140 ?mol / l, the use of cyclosporine is contraindicated.

In severely impaired liver function, the initial dose of cyclosporine should be reduced by 25-50%. For patients with GCS-resistant nephrotic syndrome in the case of insufficient effectiveness of one cyclosporine, its combination with low doses of GCS is recommended. If, after 3 months of treatment with cyclosporine, the symptoms of nephrotic syndrome persist, then the drug should be canceled.

In severe rheumatoid arthritis in the first 6 weeks of therapy, the recommended daily dose of cyclosporine is 2.5 mg / kg in 2 divided doses. If the drug is poorly tolerated, the dose can be reduced. Further, the dose is set individually, depending on the clinical manifestations of the disease and tolerance; the drug should be used in the minimum effective dose. Do not exceed a daily dose of 4 mg / kg.

In urgent cases, it is possible to increase the dose of cyclosporine up to 5 mg / kg / day.

Cyclosporin can be prescribed in combination with low doses of corticosteroids and / or NSAIDs. In the absence of a therapeutic effect after 3 months of treatment, the drug should be canceled. In severe forms of atopic dermatitis, to relieve acute symptoms of the disease, the drug is used in a daily dose of 2.5 mg / kg in 2 divided doses. If no significant improvement is observed after 2 weeks of treatment, the dose of cyclosporine should be increased to a maximum of 5 mg / kg / day. In the single most severe cases, cyclosporine is required at an initial dose of 5 mg / kg. With improvement, the daily dose should be gradually reduced. If after 6 weeks of treatment there is no significant improvement or the effective doses do not correspond to those recommended above, the drug should be discontinued. As a rule, therapy for 6-8 weeks is sufficient for the disappearance of the clinical symptoms of the disease.

Soft capsules

1 caps. cyclosporine

• uncontrolled arterial hypertension;

• malignant neoplasms and precancerous skin diseases;

• lactation period (breastfeeding);

• children's age up to 1 year;

• childhood (for the treatment of psoriasis and rheumatoid arthritis);

• hypersensitivity to the components of the drug (including polyoxyethylated castor oil).

• With caution, hyperkalemia; hyperuricemia; liver disease; Behcet's disease with neurological manifestations; traumatic brain injury or brain disease, epilepsy; viral diseases, incl. chickenpox (existing or recently transferred, including recent contact with the patient), shingles (due to the risk of generalization of the process); arterial hypertension; alcoholism; elderly patients; pediatric patients.

pharmachologic effect

An immunosuppressant is a cyclic polypeptide of 11 amino acids. Has a selective effect on T-lymphocytes. Inhibits the activation of calcineurin lymphocytes in the G0 or G1 phase of the cell cycle. This prevents the activation of T-lymphocytes and, at the cellular level, antigen-dependent release of lymphokines, including interleukin-2 (T-lymphocyte growth factor). Cyclosporine acts specifically and reversibly on lymphocytes. Unlike cytostatics, it does not suppress hematopoiesis and does not affect the function of phagocytes. Cyclosporin increases the lifespan of allogeneic transplants of skin, heart, kidney, pancreas, bone marrow, small intestine, lungs. Cyclosporin also inhibits the development of cellular reactions in relation to the allograft, skin reactions of delayed-type hypersensitivity,experimental allergic encephalomyelitis, Freund's adjuvant arthritis, graft versus host disease (GVHD), and T lymphocyte dependent antibody production. Cyclosporine has been shown to be effective in human bone marrow and solid organ transplants for the prevention and treatment of rejection and GVHD, as well as in the treatment of various conditions that are inherently autoimmune or could be considered as such.which are autoimmune in nature or can be considered as such.which are autoimmune in nature or can be considered as such.

Side effect

On the part of the digestive system: a feeling of heaviness in the epigastric region, loss of appetite, nausea (especially at the beginning of treatment), vomiting, diarrhea, pancreatitis, gum edema, liver dysfunction are possible. From the nervous system: headache, tremor, paresthesia, hyperesthesia, epileptic syndrome, lethargy, disorientation, agitation, sleep disturbance, impaired consciousness, visual disturbances; rarely - edema of the optic discs. From the side of the cardiovascular system: increased blood pressure. From the urinary system: renal dysfunction, nephropathy, interstitial fibrosis, hematuria. From the side of metabolism: hyperlipidemia, hyperuricemia, hyperkalemia, hypomagnesemia; rarely, hyperglycemia. From the endocrine system: hypertrichosis, reversible dysmenorrhea and amenorrhea. From the musculoskeletal system:rarely - muscle spasms, muscle weakness, myopathy. From the side of the hematopoietic system: slight anemia; rarely, thrombocytopenia. Allergic reactions: skin rash, respiratory distress syndrome; rush of blood to the skin of the face and upper body, bronchospasm, decreased blood pressure, tachycardia; in severe cases, shock. The occurrence of allergic reactions may be associated with the presence of polyoxyethylated castor oil in some dosage forms. Others: fatigue, edema syndrome, weight gain, burning sensation in the hands and feet. Lymphoproliferative diseases after transplantation: lymphoma, malignant skin diseases.rush of blood to the skin of the face and upper body, bronchospasm, decreased blood pressure, tachycardia; in severe cases, shock. The occurrence of allergic reactions may be associated with the presence of polyoxyethylated castor oil in some dosage forms. Others: fatigue, edema syndrome, weight gain, burning sensation in the hands and feet. Lymphoproliferative diseases after transplantation: lymphoma, malignant skin diseases.rush of blood to the skin of the face and upper body, bronchospasm, decreased blood pressure, tachycardia; in severe cases, shock. The occurrence of allergic reactions may be associated with the presence of polyoxyethylated castor oil in some dosage forms. Others: fatigue, edema syndrome, weight gain, burning sensation in the hands and feet. Lymphoproliferative diseases after transplantation: lymphoma, malignant skin diseases.malignant skin diseases.malignant skin diseases.

Application during pregnancy and lactation

Experience with cyclosporine in pregnancy is limited. The data obtained from patients after transplantation show that, compared with traditional methods of treatment, cyclosporine does not increase the risk of adversely affecting the course and outcome of pregnancy. Cyclosporin is excreted in breast milk. If necessary, use during lactation should stop breastfeeding. Experimental studies have shown that cyclosporine has no teratogenic effect.

Application for violations of liver function

In patients with impaired liver function, the topical use of cyclosporine in ophthalmology has not been studied.

Application for impaired renal function

Contraindicated in renal impairment (with the exception of patients with nephrotic syndrome). In patients with impaired renal function, the topical use of cyclosporine in ophthalmology has not been studied.

Application in children

It is contraindicated for use in children under the age of 1 year.

Drug interactions

Potassium supplements or potassium-sparing diuretics - increase the risk of developing hyperkalemia. ACE inhibitors, antiviral drugs, antibiotics of the aminoglycoside group, cephalosporins, amphotericin B, trimethoprim, co-trimoxazole, colchicine, ciprofloxacin, melphalan - increased nephrotoxicity of cyclosporin. NSAIDs - the risk of side effects from the kidneys. In patients receiving cyclosporine, there is a significant increase in the bioavailability of diclofenac, with the possible development of reversible renal dysfunction. The increase in the bioavailability of diclofenac is apparently associated with the inhibition of its metabolism during the 'first pass' through the liver. A decrease in the clearance of digoxin, colchicine, lovastatin, pravastatin, simvastatin, prednisolone is possible, which can lead to increased toxic effects:glycosidic intoxication with the use of digoxin and manifestations of toxicity of colchicine, lovastatin, pravastatin and simvastatin in relation to muscles, in particular the appearance of muscle pain, weakness, myositis and, in rare cases, rhabdomyolysis. Drugs that increase the concentration of cyclosporin in plasma - erythromycin, clarithromycin, josamycin, doxycycline, chloramphenicol, roxithromycin, midecamycin, ketoconazole, fluconazole (apparently in high doses), itraconazole, diltiazem, verapamidar, amylopamidar, ; oral contraceptives; danazol; methylprednisolone (high doses); allopurinol; amiodarone; cholic acid and its derivatives. Drugs that cause a decrease in the concentration of cyclosporine in plasma - barbiturates, carbamazepine, phenytoin; metamizole, nafcillin, sulfadimidine when administered intravenously; rifampicin,griseofulvin, terbinafine, octreotide, probucol, orlistat, troglitazone, preparations containing St. John's wort (Hypericum perforatum). Prednisolone, methylprednisolone - it has been noted that cyclosporine reduces the clearance of prednisolone, and treatment with high doses of prednisolone can increase the concentration of cyclosporine in the blood. Methylprednisolone increases the concentration of cyclosporine in the blood. Glibenclamide - it is possible to increase the concentration of cyclosporine in the blood plasma in an equilibrium state. Diuretics - the risk of developing renal dysfunction increases. Doxorubicin - an increase in the concentration of doxorubicin in the blood plasma and an increase in its toxicity. Methotrexate - an increase in the concentration of cyclosporine in the blood plasma, an increase in the incidence of nephrotoxic effects and arterial hypertension.Melphalan (with intravenous administration in high doses) - the development of severe renal failure is possible. Teniposide - a decrease in the clearance of teniposide, an increase in its T1 / 2, an increase in toxicity. Warfarin - a decrease in the effectiveness of cyclosporin and warfarin. Enalapril - development of acute renal failure is possible. Nifedipine - increased gingival hyperplasia. Cisapride - an increase in its Cmax of cyclosporine in blood plasma and the rate of absorption. Quinidine and its derivatives, theophylline and its derivatives - it is possible to enhance the effects of quinidine and its derivatives, theophylline and its derivatives. Imipinema in combination with cilastatin - an increase in the concentration of cyclosporine is possible, which can lead to the appearance of symptoms of neurotoxicity (tremors, increased excitability). Other immunosuppressants - increase the risk of developing infections and lymphoproliferative diseases.