Equoral, 50mg capsules, 50pcs

Composition

1 capsule contains: Active ingredients: cyclosporine 50 mg, excipients: ethyl alcohol; macrogol glyceryl hydroxystearate; polyglyceryl (3) oleate; polyglyceryl (10) oleate; D, L-alpha-tocopherol.

Pharmacological action

Equoral has an immunosuppressive effect.

At the cellular level, it suppresses the formation and release of lymphokines, including IL-2 (T-cell growth factor). Blocks resting lymphocytes in the G0 or G1 phase of the cell cycle and suppresses the antigen-dependent release of lymphokines by activated T-lymphocytes. All the data obtained indicate that cyclosporine has a specific and reversible effect on lymphocytes.

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

Pharmacokinetics

After oral use, Cmax in the blood is noted in the range from 1 to 6 hours, and bioavailability is on average 30% (20-50%) and increases with increasing dose and duration of treatment. Absorption decreases after liver transplantation, in cases of liver diseases or gastrointestinal disorders (diarrhea, vomiting, intestinal obstruction).

Intensely binds to proteins and shaped blood elements (the concentration in whole blood is 2-9 times higher than in plasma). Protein binding is 90% (mainly 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 red blood cells. After oral use, Tmax in plasma is 1.5-3.5 hours. It is intensively metabolized in the liver by cytochrome P 4503 A, to a lesser extent in the gastrointestinal tract and kidneys with the formation of 15 identified metabolites. It is excreted in the bile, kidneys and urine — 6% of the oral dose. It is excreted in breast milk.

T 1/2 in adults — 19 hours, in children-7 hours, regardless of the dose or route of use.

Indications

Graft — versus-host response (GVHD) – prevention and treatment; autoimmune diseases.

Indications related to transplantation: solid organ transplantation (prevention of graft rejection after allogeneic transplantation of kidney, liver, heart, heart — lung combination drug, lung or pancreas; treatment of graft rejection in patients previously treated with other immunosuppressants; bone marrow transplantation (prevention of graft rejection after bone marrow transplantation, prevention and treatment of GVHD.

Indications not related to transplantation: endogenous uveitis (active, vision-threatening uveitis of the middle and posterior eye of 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 (steroid-dependent and steroid-resistant forms in remission); rheumatoid arthritis (severe forms), psoriasis (severe forms when systemic therapy is required therapy).

Use during pregnancy and lactation

Experience with cyclosporine in pregnant women is limited.

Data obtained from patients in the post-transplant period show that cyclosporine treatment increases the risk of negative effects on the course and outcome of pregnancy.

If it is necessary to prescribe Equoral, stop breastfeeding.

Contraindications

Hypersensitivity to the components of the drug, malignant neoplasms and precancerous skin diseases, chickenpox, Herpes zoster (risk of generalization of the process), severe liver failure, hyperkalemia, hypertension, malabsorption syndrome, infectious diseases in the acute phase.

Side effects

In the first week of using Equoral, a burning sensation may occur on the skin of the extremities.

After organ transplantation, the most common symptoms are: hypertrichosis, tremor, impaired renal function and liver dysfunction, gum hypertrophy, gastrointestinal disorders (anorexia, nausea, vomiting); dose-dependent and reversible increase in serum creatinine, urea, bilirubin, and liver enzymes (careful monitoring of parameters and correction of cyclosporine dosage is necessary).

With a heart transplant, hypertension is most often developed, with a kidney transplant, this side effect occurs less often.

When bone marrow transplants occur most often: gastrointestinal disorders, tremor, hypertrichosis, possible swelling of the face. In children, edema and convulsions are noted.

Side effects are moderate and usually eliminated with a decrease in the dosage of Equoral.

Interaction

Cytochrome P450 inducers or inhibitors can reduce or increase the concentration of cyclosporine in the blood.

Drugs that reduce the concentration of cyclosporine: barbiturates, carbamazepine, phenytoin, nafcillin, sulfadimidine (with intravenous use); rifampicin, octreotide, probucol, orlistat; drugs containing St. John’s wort (Hypericum perforatum); troglitazone.

Drugs that increase the concentration of cyclosporine: some macrolide antibiotics (mainly erythromycin and clarithromycin); ketoconazole, fluconazole, itraconazole, diltiazem, nicardipine, verapamil, metoclopramide, oral contraceptives, danazol, methylprednisolone (high doses); allopurinol, amiodarone, cholic acid and its derivatives.

Oral use 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 cyclosporine in the blood, kidney function and the presence of side effects of cyclosporine.

Caution should be exercised when concomitantly prescribing drugs with nephrotoxic effects, for example: aminoglycosides (including gentamicin, tobramycin), amphotericin B, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole), NSAIDs (including diclofenac, naproxen, sulindac), melphalan.

During cyclosporine treatment, vaccination may be less effective; live attenuated vaccines should be avoided.

Combined use with nifedipine may lead to more pronounced gum hyperplasia than with cyclosporine monotherapy.

May significantly increase the bioavailability of diclofenac (probably due to decreased metabolism) with the possible development of reversible renal impairment.

It can reduce the clearance of digoxin, colchicine, lovastatin and prednisone, leading to increased toxic effects, in particular muscle pain, weakness, myositis and, in rare cases, rhabdomyolysis.

How to take, course of use and dosage

Inside. Equoral capsules should be swallowed whole, washed down with water. The daily dose is divided into 2 doses. The Equoral dose ranges listed below are just recommendations. The concentration of cyclosporine in the blood should be monitored. Based on the results obtained, the dose required to achieve the desired level of cyclosporine concentration in various patients is determined.

Adults with bone marrow transplantation on the day preceding the transplant, the drug Equoral is administered intravenously at a dose of 3-5 mg per kg of body weight per day, then continued at the same dose for 2 weeks, and then switched to maintenance therapy in capsules.

When transplanting organs,4-12 hours before the operation, they are prescribed once at a dose of 3-5 mg per kg of body weight, then within 1-2 weeks after the operation, the drug Equoral is prescribed daily at 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.

Overdose

Data on overdose with the drug are currently unavailable and there is limited experience with overdose with other cyclosporines.

Symptoms:  impaired renal function, which is probably reversible and disappears after discontinuation of the drug.

Treatment:  based on indications — general support activities. The drug can be eliminated from the body only by non-specific measures, including gastric lavage, since hemodialysis and hemoperfusion using activated carbon are ineffective.

Special instructions

Data on the experience of using the drug in the elderly are quite limited, but to date, no deviations have been registered in the condition of patients who took the drug at the recommended dose.

If a patient is treated with cyclosporine with an increase in blood pressure, an increase in creatinine levels (by more than 30% from the initial value), it is necessary to reduce the dose by 25-50%.

If it is impossible to control the side effect or in case of severe renal impairment, the drug is discontinued.

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Cyclosporine

Conditions of release from pharmacies

By prescription

Dosage form

Capsules