Expiration date: 04/2025
The composition and form of issue:
Capsules, 1 capsule contains:
cyclosporine 25 mg
excipients: ethyl alcohol and 39.9 mg macrogol glyceryl hydroxystearate — 73,7 mg polyglyceryl (3) oleate — 82,7 mg polyglycerol (10) oleate — 50.0 mg D,L-alpha-tocopherol — 0.25 mg
softgel capsule shell: gelatin — 95,1 mg glycerol 85% — 44,3 mg solution of sorbitol and 8.6 mg of iron oxide yellow 0.1 mg titanium dioxide 0.8 mg glycine — 1.1 mg
Capsules, 1 capsule contains:
cyclosporine 50 mg
excipients: hydroxystearate — 147,4 mg polyglyceryl (3) oleate — was 165.3 mg polyglycerol (10) oleate 100 mg D,L-alpha-tocopherol — 0.5 mg
softgel capsule shell: gelatin — 222,2 mg glycerol 85% were 103.8 mg solution of sorbitol — and 20.2 mg of iron oxide yellow 0.8 mg titanium dioxide 0.5 mg glycine 2.5 mg
Capsules, 1 capsule contains:
cyclosporine 100 mg
excipients: ethyl alcohol — 159,6 mg macrogol glyceryl hydroxystearate — 294,7 mg polyglyceryl (3) oleate — 330,7 mg polyglycerol (10) oleate — 199,9 mg D,L-alpha-tocopherol 1 mg
softgel capsule shell: gelatin — 315,2 mg glycerol 85% — and 148.3 mg solution of sorbitol, accounting for 28.7 mg iron oxide brown — 0.7 mg titanium dioxide and 3.6 mg glycine, 3.6 mg
in packing contour cell 10 PCs. in cardboard pack of 5 packs.
The oral solution 100 mg/ml 1 ml
cyclosporine 100 mg
excipients: ethanol 120 mg macrogolglycerol hydroxystearate — 280 mg of polyglycerol (3) oleate — 310 mg of polyglycerol (10) oleate — 190 mg
in a bottle of dark glass 50 ml in box plastic 1 bottle.
Description pharmaceutical form:
Capsules 25 mg: opaque, yellow, 12,5×8 mm, soft, oval, gelatin capsules.
Capsules 50 mg: opaque, brown-yellow, 21×8 mm, oblong soft gelatin capsules.
Capsules 100 mg: opaque, brown, 26×8 mm, oblong soft gelatin capsules.
Each dosage capsules identificireba printed on the double triangle and the text: "25 mg", "50 mg", "100 mg".
The contents of capsules — transparent oily liquid from yellow to yellow-brown. Each dosage capsules labeled IVAX and printed text: "25 mg", "50 mg" and "100 mg", respectively.
The oral solution 100 mg/ml: clear, yellowish to yellow-brown oily liquid.
Feature:
Is a cyclic polypeptide consisting of 11 amino acids.
Pharmacological action:
At the cellular level suppresses the formation and release of lymphokines including IL-2 (growth factor of T lymphocytes). Blocks the lymphocytes in the resting phase G0 or G1 of the cell cycle and suppresses antigistaminnoe the release of lymphokines by activated T-lymphocytes. All the data obtained indicate that cyclosporine acts on lymphocytes specific and reversible.
Does not suppress haematopoiesis and has no effect on the function of phagocytic cells.
Pharmacokinetics:
Once inside C max in the blood is in the range of from 1 to 6 h, with a bioavailability of approximately 30% (20-50%) and increases with increasing dose and duration of treatment. The absorption decreases after liver transplantation, liver diseases or pathology of the gastrointestinal tract (diarrhea, vomiting, intestinal obstruction).
Intensive contacts with proteins and formed elements of the blood (concentration in whole blood is 2 to 9 times higher than in plasma). The relationship with the squirrels — 90% (predominantly lipoproteins). Distributed mainly outside blood bed: in the plasma there is 33-47%, lymphocytes — 4-9%, granulocytes — 5-12%, in erythrocytes — 41-58%. After ingestion Tmax in plasma is 1.5–3.5 h. Intensive metabolised in the liver by cytochrome ?4503?, to a lesser extent in the gastrointestinal tract and kidneys with the formation of the 15 identified metabolites. Bile is excreted by kidneys with urine — 6% of the ingested dose. Excreted in breast milk.
T1/2 in adults — 19 h, in children, 7 h, regardless of dose or route of administration.
Indications:
Reaction "graft versus host" disease (GVHD) — prophylaxis and treatment of autoimmune diseases.
Readings related to transplantation: transplantation of solid organs (prevention of graft rejection after allogeneic transplantation of kidney, liver, heart, combined medication heart — lung, lung or pancreas treatment of graft rejection in patients previously receiving other immunosuppressive agents bone marrow transplantation (prevention of graft rejection after bone marrow transplantation, prevention and treatment of GVHD.
Readings that are not related to transplantation: endogenous uveitis (active, sight-threatening uveitis intermediate and posterior eye non-infectious etiology, if conventional therapy is unsuccessful or leads to severe adverse reactions), Behcet's uveitis with recurrent attacks of inflammation affecting the retina nephrotic syndrome (steroidzawisimaya and steroid-resistant forms in remission) rheumatoid arthritis (severe), psoriasis (severe form when it is required systemic therapy).
Contraindications:
Hypersensitivity to the drug, malignant tumors and precancerous lesions of the skin, chickenpox, Herpes zoster (risk of generalization), severe impairment of liver function, hyperglycaemia, hypertension, malabsorption syndrome, infectious diseases in acute phase.
Application of pregnancy and breast-feeding:
Experience with the use of cyclosporine in pregnant women is limited. Data obtained in patients in the posttransplantation period suggest that treatment with cyclosporine increases the risk of negative impact on the course and outcome of pregnancy. If necessary, the appointment Akurala should stop breastfeeding.
Side effects:
In the first week of using the drug may feel a burning sensation on the skin of the extremities. After transplantation of organs occur most often: hypertrichosis, tremor, impaired renal function and dysfunction of the liver, hypertrophy of the gums, disorders of the gastrointestinal tract (anorexia, nausea, vomiting) a dose-dependent and reversible increase in creatinine, urea, bilirubin, liver enzymes in serum (careful monitoring of parameters and a correction of the dosage of cyclosporine).
When heart transplantation is most often develops hypertension, in kidney transplants this side effect happens less.
When a bone marrow transplant is most often occur: gastrointestinal disorders, tremor, hypertrichosis, possible swelling of the face. In children, marked edema, and seizures.
Adverse reactions are mild and usually eliminated by reducing the dosage of the drug.
Drug interactions:
Inducers or inhibitors of cytochrome P450 can decrease or increase the concentration of cyclosporine in the blood.
Drugs that reduce the concentration of cyclosporine: barbiturates, carbamazepine, phenytoin, nafcillin, sulfadimidine (at/in the introduction) rifampicin, octreotide, probucol, orlistat products containing St. John's wort (Hypericum perforatum) troglitazone.
Drugs that increase the concentration of cyclosporine, some antibiotics — macrolides (primarily erythromycin and clarithromycin) ketoconazole, fluconazole, Itraconazole, diltiazem, nicardipine, verapamil, metoclopramide, oral contraceptives, danazol, methylprednisolone (high dose), allopurinol, amiodarone, cholic acid and its derivatives.
Should be avoided inside erythromycin (increases the concentration of cyclosporine in the blood). If, due to the lack of alternative therapies, erythromycin assigned, it is recommended to carefully control the concentration of cyclosporine in the blood, kidney function and the presence of side effects of cyclosporine.
Caution should be exercised with concomitant administration of drugs with nephrotoxic effects, e.g. aminoglycosides (including gentamicin, tobramycin), amphotericin b, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole), NSAIDs (including diclofenac, naproxen, sulindac), melphalan.
During treatment with cyclosporine vaccination may be less effective avoid the use of live attenuated vaccines.
The concomitant use with nifedipine may lead to more pronounced, than at monotherapy with cyclosporine, gingival hyperplasia.
Can significantly increase the bioavailability of diclofenac (probably due to lower metabolism) with possible development of reversible renal dysfunction.
May decrease the clearance of digoxin, colchicine, lovastatin and prednisone, leading to increased toxic effects, particularly muscle pain, weakness, myositis and, in rare cases, rhabdomyolysis.
Method of application and dose:
Inside. Capsules should be swallowed whole, washed down with water. The daily dose divided into 2 doses. The following dosage ranges of the drug — this is only a recommendation. Should be monitoring of the concentration of cyclosporine in the blood. On the basis of obtained results determine the dose required to achieve the desired level of concentration of cyclosporine in different patients.
Transplantation
When transplanting solid organs the drug is administered for 12 h before surgery at a dose of 10-15 mg/kg/day, divided into 2 doses. Within 1-2 weeks after surgery, the drug is administered daily at the same dose, and then, under the control of the concentration of cyclosporine in the blood, gradually to be reduced to achieve a maintenance dose 2-6 mg/kg/day in 2 admission.
In cases where Ekoral administered in combination with glucocorticoids, as well as the composition of three-component or four-component therapy, the dose may be reduced even at the initial stage of therapy (3-6 mg/kg/day in 2 doses) or adjusted in the course of treatment given the concentration of cyclosporine in the blood and the dynamics of safety indicators (concentrations of urea, creatinine, serum and AD).
When bone marrow transplantation the initial dose should be assigned the day before surgery. Daily dose of 12.5 mg/kg in 2 admission. Supportive therapy for at least 3 months (preferably 6 months), after which the dose of cyclosporine was gradually reduced during the year.
Readings that are not associated with transplantation
Endogenous uveitis: to achieve remission, the initial daily dose of 5 mg/kg in 2 admission to the disappearance of signs of inflammation and improvement of visual acuity. In cases difficult to therapy, the dose can be increased for a short time up to 7 mg/kg/day. With the ineffectiveness of monotherapy Emralon to the comprehensive treatment of add systemic glucocorticoids in a daily dose 0.2–0.4 mg/kg of prednisone (or another glucocorticoid drug in equivalent dosage). Upon reaching clinical effect dose Akurala gradually slowly reduced to the lowest effective dose, which in the period of remission should not exceed 5 mg/kg/day.
Nephrotic syndrome: for the achievement of remission the recommended daily dose of 5 mg/kg for adults and 6 mg/kg for children (2 doses), assuming normal renal function. Impaired renal function the initial dose should not exceed 2.5 mg/kg/day. With the ineffectiveness of monotherapy Earlom, especially in steroid-resistant patients, the drug should be combined with oral glucocorticoids in low doses. In the absence of clinical effect within 3 months Ekoral should be abolished.
Rheumatoid arthritis: for the first 6 weeks of treatment the recommended dose is 3 mg/kg/day in 2 admission. In case of failure and permitting the tolerability, the daily dose may be gradually increased, but not more than 5 mg/kg For maintenance therapy dose picked individually, depending on tolerability. Ekoral can be combined with low doses of corticosteroids and/or NSAIDs, with a weekly course of methotrexate in low doses in patients with unsatisfactory response to monotherapy latest. Akurala initial dose is 2.5 mg/kg/day (2 admission), dose can be increased to a level limited by tolerability.
Psoriasis: treatment is chosen individually, the recommended starting dose for induction of remission 2.5 mg/kg/day in 2 admission. If no improvement within 1 month of treatment the daily dosage can be increased but not more than 5 mg/kg If after 6 weeks treatment with dose of 5 mg/kg/day were unsuccessful or effective dose does not meet the established security settings, the drug should be stopped. The use of an initial dose of 5 mg/kg/day is justified in patients whose condition requires immediate improvement. If a satisfactory effect is achieved, Ekoral can be canceled, and subsequent relapse to treat the re-appointment of the drug in the previous effective dose. Some patients may require prolonged maintenance therapy (dose adjusted individually to the minimum effective level and must not exceed 5 mg/kg/day).
Atopic dermatitis: the recommended initial dose range is 2.5–5 mg/kg/day in 2 admission. If initial dose 2.5 mg/kg/day does not achieve a satisfactory response within 2 weeks, the daily dose can be rapidly increased to a maximum of 5 µg/kg In very severe cases rapid and adequate effect in the treatment of the disease can be achieved by applying a starting dose of 5 mg/kg/day. After achieving satisfactory response, the dose is gradually reduced and, if possible, cancel the drug. If you experience relapse, a second course. Despite the fact that the 8-week course of treatment may be enough for cleansing of skin, it was shown that therapy for up to 1 year is effective and well tolerated, with mandatory monitoring of all necessary parameters.
Overdose:
Data on overdose with the drug to date are absent and there is limited experience with overdose of other cyclosporines.
Symptoms: renal dysfunction, which are likely reversible and disappear after discontinuation of the drug.
Treatment: indications — General supportive measures. The drug can be removed from the body only by means of non-specific measures including gastric lavage as hemodialysis and hemoperfusion using activated charcoal is ineffective.
Precautions:
Due to the possible interaction with the enzyme system cytochrome P450 should not be consumed one hour before dosing grapefruit or grapefruit juice.
Special instructions:
Data about the use of the drug in the elderly is rather limited, however, to date not registered any abnormalities in the condition of patients who took the drug at the recommended dose.
If the patient is on the background of treatment with cyclosporine increase blood pressure, increase in serum creatinine (more than 30% of the original value) requires a dose reduction of 25-50%. If it is impossible to control the side effect or in case of severe renal dysfunction, the drug overturned.
At temperatures below +20 °C the solution has the consistency to resemble a gel, and sedimentation may occur, which disappears when the temperature rises to +20 °C, however, may remain a small amount of cereal or light sedimentation. These phenomena do not affect the efficacy and safety of the drug, and the dosage using the measuring syringe remains accurate.
