Ecoral capsules 50mg n50

Dosage Form

soft capsules

Composition

cyclosporine 50 mg

Excipients: ethanol, macrogolglycerol hydroxystearate, polyglyceryl-3-oleate, polyglyceryl-10-oleate, D, L -? - tocopherol.

Shell composition: gelatin, glycerol 85%, sorbitol solution, ferric oxide yellow, titanium dioxide, Glycine

Mechanism of action

Immunosuppressive drug. Ecoral (cyclosporin A) is a cyclic polypeptide consisting of 11 amino acids.

At the cellular level, cyclosporine inhibits the formation and release of lymphokines, including interleukin-2 (T-cell growth factor). Cyclosporin blocks lymphocytes at rest in the G0 or G1 phase of the cell cycle and inhibits the antigen-dependent release of lymphokines by activated T-lymphocytes. All the data obtained indicate that cyclosporin acts on lymphocytes specifically and reversibly.

Cyclosporine does not inhibit hematopoiesis and does not affect the function of phagocytic cells.

Pharmacokinetics

Suction

After taking cyclosporine inside its Cmax in the blood plasma is observed in the range from 1 to 6 hours, with its bioavailability averaging 30% (from 20 to 50%) and increasing with increasing dose and duration of treatment. Absorption decreases after liver transplantation, in liver diseases or gastrointestinal tract pathology (diarrhea, vomiting, ileus).

Distribution

Intensively binds to proteins and blood cells (the concentration in whole blood is 2-9 times higher than in plasma); however, binding to plasma proteins is 90% (mainly with lipoproteins). Distribution mainly outside the bloodstream; 33–47% is present in plasma, 4–9% in lymphocytes, 5–12% in granulocytes, and 41–58% in erythrocytes. It is excreted in breast milk.

Metabolism

It is metabolized in the liver by cytochrome P450 3A, to a lesser extent by the gastrointestinal system, by the kidneys, with the formation of 15 identified metabolites.

Removal

Excreted in the bile; kidneys - 6% of the administered oral dose. T1 / 2 - 19 hours in adults and 7 hours in children, regardless of the dose or route of administration.

Side effects

Cyclosporine adverse reactions are mild and usually disappear when the dose is lowered.

After starting the drug inside the first week, patients may experience a burning sensation of the skin of the extremities.

In solid organ transplantation, the most common are: enhanced hair growth, tremor, impaired kidney and liver function, gum hypertrophy, and disorders of the digestive system (anorexia, nausea, vomiting, dose-dependent and reversible increases in bilirubin and serum liver enzymes); There is also a dose-dependent and reversible increase in creatinine and urea.

During heart transplantation, hypertension is the most common (renal transplantation is less common).

For bone marrow transplantation: gastrointestinal disorders, tremor, hypertrichosis, possible swelling of the face. Children have swelling and cramps.

Sales features

prescription

Special conditions

Experience with the use of the drug in the elderly is limited, but so far no deviations in the condition of the patients taking the drug in the recommended dose have been noted.

With an increase in blood pressure on the background of the use of the drug or an increase in the level of creatinine by more than 30% from the initial dose, it is necessary to reduce the dose of Ecoral by 25-50%. If it is impossible to monitor the patient's condition or in case of more severe renal dysfunction, the drug is canceled.

Indications

Cyclosporine is used in the transplantation of allogeneic solid organs and bone marrow for the prevention and treatment of graft versus host disease (GVHD), as well as for autoimmune diseases.

Transplantation

-transplantation of solid organs: prevention of transplant rejection after allogeneic transplantation of a kidney, liver, heart, heart-lung, lung or pancreas combined preparation. Treatment of transplant rejection in patients previously treated with other immunosuppressants;

- bone marrow transplantation: prevention of transplant rejection after bone marrow transplantation; prevention and treatment of GVHD.

Non-transplanted indications

Endogenous uveitis (active, eye-threatening uveitis of the middle and posterior part of the eye of non-infectious etiology,if conventional therapy does not produce a result or leads to severe adverse reactions), Behcet's uveitis (with recurrent bouts of inflammation affecting the retina);

Contraindications

malignant neoplasms and precancerous skin diseases;

-chickenpox;

- shingles (risk of generalization of the process);

Severe liver failure;

- hyperkalemia;

- uncontrolled arterial hypertension;

malabsorption syndrome;

-infectious diseases in the acute phase;

Increased sensitivity to the components of the drug.

Drug interaction

The following are the drugs for which interaction with cyclosporine is confirmed and clinically significant.

Various drugs can increase or decrease the concentration of cyclosporine in the blood plasma due to the suppression or induction of enzymes involved in the metabolism of cyclosporine, in particular, cytochrome P450 isoenzymes.

When combined with Ecoram barbiturates, Carbamazepine, phenytoin, nafcillin, sulfadimidin (with a / in the introduction), rifampicin, Octreotide, probucol, orlistat; drugs containing St. John's wort (Hypericum perforatum), troglitazone reduce the concentration of cyclosporine in the blood plasma.

When used together, some macrolide antibiotics (mainly Erythromycin and clarithromycin), Ketoconazole, Fluconazole, itraconazole, diltiazem, nicardipine, Verapamil, Metoclopramide, oral contraceptives, danazol, methylprednisolone (high doses), allopuristrin, high concentrations, allopurin, allopurin, allopurin.

Instructions for use

Dosage Ecoral

The daily dose of Echoral should be divided into 2 doses.The following dose ranges for taking oral Ecorul should be considered only as recommendations. The generally accepted monitoring of the concentration of cyclosporine in the blood should be carried out. Based on the results, determine the dose required to achieve the desired level of concentration of cyclosporine in different patients. Ecorul capsules should be taken with water and swallowed whole. Because of the possible interaction with the P450-dependent enzyme system, grapefruit or grapefruit juice should not be consumed 1 hour before taking the dose of the drug. Transplantation During transplantation of solid organs, Ecorel treatment should be started 12 hours before the operation at a dose of 10-15 mg / kg, divided into 2 doses. Within 1-2 weeks after surgery, the drug is prescribed under the control of the concentration of cyclosporine in the blood, until a maintenance dose of 2-6 mg / kg / is reached (in 2 doses). In cases where the Ecoral is prescribed in combination with GCS, as well as as part of three-component or four-component therapy, the dose of the drug can be reduced even at the initial stage of therapy (3-6 mg / kg / 2 doses) or adjusted in the course of treatment taking into account concentration of cyclosporine in the blood and the dynamics of safety indicators (concentration of urea, serum creatinine and blood pressure). For bone marrow transplantation, the initial dose should be prescribed one day before the operation. The daily dose of Ecoral should be 12.5 mg / kg divided into 2 doses.Maintenance therapy is carried out for at least 3 months (preferably 6 months), after which the dose of cyclosporine is constantly reduced to zero for 1 year. Indications not related to transplantation With endogenous uveitis, to achieve remission, the drug is prescribed in an initial daily dose of 5 mg / kg orally in 2 divided doses until signs of active inflammation disappear and visual acuity improves. In cases difficult to treat, the dose may be increased to 7 mg / kg / for a short period. If it is not possible to control the situation with the use of Echoral monotherapy, then to achieve initial remission or to relieve an attack of inflammation, systemic corticosteroids can be added to the complex therapy in a daily dose of 0.2-0.6 mg / kg of prednisolone (or another GCS drug in an equivalent dose). During maintenance therapy, the dose should be slowly reduced until the smallest effective dose is reached, which should not exceed 5 mg / kg during the remission of the disease. For nephrotic syndrome, the recommended daily dose is 5 mg / kg for adults and 6 mg / kg for children. (in 2 doses), provided normal kidney function. In patients with impaired renal function, the initial dose should not exceed 2.5 mg / kg / If, when using Echoral alone, a satisfactory effect cannot be achieved, especially in steroid-resistant patients, it is recommended to combine it with oral GCS in low doses.