Description
Release form
Capsules
Packing
50 pcs.
Pharmacological action
Ecoral has an immunosuppressive effect.
At the cellular level, inhibits the formation and release of lymphokines, including IL-2 (T-lymphocyte growth factor). Blocks lymphocytes at rest in the G0 or G1 phase of the cell cycle and inhibits antigen-dependent release of lymphokines by activated T-lymphocytes. All the data obtained indicate that cyclosporine acts on lymphocytes specifically and reversibly.
Does not inhibit hematopoiesis and does not affect the function of phagocytic cells.
Pharmacokinetics of
After oral administration, Cmax in the blood is observed in the range from 1 to 6 hours, with bioavailability averaging 30% (20 50%) and increases with increasing dose and duration of treatment. Absorption decreases after a liver transplant, with liver diseases or gastrointestinal pathology (diarrhea, vomiting, intestinal obstruction).
Intensively binds to proteins and blood cells (concentration in whole blood is 2 9 times higher than in plasma). Communication with proteins – 90% (mainly with lipoproteins). It is distributed mainly outside the bloodstream: 33 47% is present in plasma, 4 9% in lymphocytes, 5 12% in granulocytes, and 41 58% in erythrocytes. After oral administration, Tmax in plasma is 1.5 3.5 hours. It is intensively metabolized in the liver by cytochrome P4503A, to a lesser extent in the digestive tract and kidneys with the formation of 15 identified metabolites. It is excreted with bile by the kidneys with urine – 6% of the dose administered orally. Excreted in breast milk.
T1 / 2 in adults – 19 hours, in children – 7 hours, regardless of dose or route of administration.
Indications
Graft versus Host GVHD (GVHD) – Prevention and treatment of autoimmune diseases.
Indications related to transplantation: solid organ transplantation (prevention of transplant rejection after allogeneic transplantation of a kidney, liver, heart, combined drug heart – lung, lung, or pancreas, treatment of transplant rejection in patients, previously treated with other immunosuppressants bone marrow transplantation (prophylaxis of transplant rejection after bone marrow transplantation, prevention and treatment of GVHD.
Indications not related to transplantation: endogenous uveitis (active, threatening vision, uveitis of the middle and posterior part of the eye of a non-infectious etiology if conventional therapy is unsuccessful or leads to severe adverse reactions), Behcet’s uveitis with recurrent bouts of inflammation affecting the retina nephrotic syndrome (steroid-dependent and steroid drezistentnaya form in remission), rheumatoid arthritis (severe), psoriasis (severe when required systemic therapy)
Contraindications
Hypersensitivity to the components of Ekoral, malignant neoplasms and precancerous skin diseases, chickenpox, Herpes zoster (risk of generalization of the process), severe insufficiency of liver function, hyperkalemia, hypertension, malabsorption syndrome, infectious diseases in the acute phase.
Use during pregnancy and lactation
Experience with cyclosporine in pregnant women is limited. Data, obtained in patients in the post-transplant period, show that treatment with cyclosporine increases the risk of adverse effects on the course and outcome of pregnancy. If necessary, the appointment of Ecoral should stop breastfeeding.
Special instructions
Data on the experience of using the drug in the elderly are quite limited, however, to date, no deviations in the condition of patients taking the drug in the recommended dose have been recorded.
If a patient has an increase in blood pressure during treatment with cyclosporine, an increase in creatinine (more than 30% of the initial value), a dose reduction of 25-50% is necessary. If it is not possible to control a side effect or in case of severe renal impairment, the drug is canceled.
Composition
1 capsule contains 25 mg cyclosporine, excipients: ethyl alcohol macrogol glyceryl hydroxystearate polyglyceryl (3) oleate polyglyceryl (10) oleate D, L-alpha-tocopherol
Dosage and Administration
Inside. Ecoral capsules should be swallowed whole, washed down with water. The daily dose is divided into 2 doses. The following dose ranges for Ekoral are just recommendations. Blood cyclosporin concentrations should be monitored. Based on the results obtained, the dose necessary to achieve the desired level of cyclosporin concentration in various patients is determined.
Adults with a bone marrow transplant on the day preceding the transplant, Ecoral is administered intravenously at a dose of 3-5 mg per kg of body weight per day, then continue at the same dose for 2 weeks, and then switch to maintenance therapy in capsules. For organ transplants, 4-12 hours before surgery, a single dose of 3-5 mg per kg of body weight is prescribed, then 1-2 weeks after surgery, Ecoral is prescribed daily in the same dose, then the dose is gradually reduced until a maintenance dose of 0.7-2 mg per kg of body weight per day is reached.
Side effects
In the first week of application of Ekoral, a burning sensation on the skin of the limbs is possible. After organ transplantation, the most common occurrences are: hypertrichosis, tremor, impaired renal function and liver dysfunction, gum hypertrophy, gastrointestinal disorders (anorexia, nausea, vomiting), dose-dependent and reversible increase in creatinine, urea, bilirubin, liver enzymes in the blood serum (careful monitoring parameters and dosage adjustment of cyclosporine).
During a heart transplant, hypertension most often develops, with a kidney transplant, this side effect is less common.
When a bone marrow transplant occurs, it most often occurs: gastrointestinal tract disorders, tremors, hypertrichosis, and swelling of the face is possible. Children have swelling and cramps.
Adverse reactions are mild and usually resolve with a reduced dosage of Ekoral.
Drug Interactions
Inducers or inhibitors of cytochrome P450 can lower or increase the concentration of cyclosporin in the blood.
Drugs that reduce the concentration of cyclosporine: barbiturates, carbamazepine, phenytoin, nafcillin, sulfadimidine (with iv) rifampicin, octreotide, probucol, orlistat preparations containing hypericum perforatum (hypericum perforatum) troglitone.
Drugs that increase the concentration of cyclosporine: some antibiotics – macrolides (mainly erythromycin and clarithromycin) ketoconazole, fluconazole, itraconazole, diltiazem, nicardipine, verapamil, metoclopramide, oral contraceptives, danazole, methylprednisolone (high doses) allopurinol, its amiodorone.
Oral administration of erythromycin should be avoided (increases the concentration of cyclosporine in the blood). If, due to the lack of alternative therapy, erythromycin is prescribed, it is recommended to carefully monitor the concentration of cyclosporin in the blood, kidney function and the presence of side effects of cyclosporin.
Caution should be exercised while prescribing drugs with a nephrotoxic effect, for example: 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, live attenuated vaccines should be avoided.
Combined use with nifedipine can lead to more pronounced gingival hyperplasia than with cyclosporine monotherapy.
May significantly increase the bioavailability of diclofenac (probably due to decreased metabolism) with the possible development of a reversible impaired renal function.
May reduce the clearance of digoxin, colchicine, lovastatin and prednisolone, leading to increased toxic effects, in particular muscle pain, weakness, myositis, and, in rare cases, rhabdomyolysis.
overdose
There are no data on overdose with the drug so far and there is limited experience with overdosage of other cyclosporins.
Symptoms: Renal dysfunction, which is likely to be reversible and disappear after drug withdrawal.
Treatment: According to indications – general supportive measures. The drug can only be excreted by non-specific measures, including gastric lavage, as hemodialysis and hemoperfusion using activated carbon are ineffective.
Storage Conditions
In a dark place at a temperature not exceeding 25 ° C.
active substance
Cyclosporin
Dosage form
capsule
Teva Pharmaceutical Enterprises Co., Ltd., Israel
