Included in the formulation
АТХ:L.04.A.A Selective immunosuppressants
L.04.A.A.10 Sirolimus
Pharmacodynamics:Sirolimus (rapamycin) is a macrolide derived from Streptomyces hygroscopicus. It blocks calcium-mediated and calcium-independent intracellular signaling when IL-2 receptors of T cells are activated, thereby inhibiting their activation. Sirolimus binds to a specific cytosolic protein - immunophilin FK-binding protein (FKBP-12). This complex interacts with the enzyme kinase mTOR (Target of Rapamycin), which is of fundamental importance for the development of the cell cycle. Inhibition of mTOR results in the blocking of several specific pathways through which the signal is transmitted upon activation of the IL-2 receptor. Ultimately, activation of lymphocytes is inhibited, which leads to immunosuppression.
Pharmacokinetics:After ingestion, up to 14% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved after 1-2 hours. For the most part it accumulates in the formed elements of the blood.
Metabolism in the liver.
The half-life is 46-78. Elimination with feces (up to 91%) and kidneys.
Indications:It is used to prevent graft rejection in combination with cyclosporine and glucocorticosteroids.
XXI.Z80-Z99.Z94 Presence of transplanted organs and tissues
Contraindications:Individual intolerance.
Carefully:Impaired liver and kidney function.
Pregnancy and lactation:Recommendations for FDA - Category C. Contraindicated in pregnancy and lactation.
Dosing and Administration:Inside in combination with glucocorticosteroids and cyclosporine for 2-3 months.
Saturated dose: 6 mg once for 2 days after transplantation, maintaining a dose of 2 mg / day.
The highest daily dose: 6 mg.
The highest single dose: 6 mg.
Side effects:Respiratory system: pneumonitis, pulmonary fibrosis.
The hemopoietic system: thrombocytopenia, anemia, hypokalemia, hyperglycemia, hypertriglyceridemia.
Cardiovascular system: lymphocele, peripheral edema.
Digestive system: abdominal pain, diarrhea.
Musculoskeletal system: arthralgia.
Dermatological reactions: acne, delayed healing of wounds, increased risk of tumor development.
Reproductive system: transient impairment of functional activity of sperm.
Allergic reactions.
Overdose:Atrial fibrillation, liver necrosis.
Treatment is symptomatic. Hemodialysis is ineffective.
Interaction:Rifampicin reduces the concentration of sirolimus in the blood.
With simultaneous use, the concentration of the drug in the blood increases inhibitors of CYP3A4: clotrimazole, intraconazole, fluconazole, verapamil, nicardipine, erythromycin, metoclopramide, cimetidine, ritonavir, indinavir.
Inductors CYP3A4: phenobarbital, rifabutin, carbamazepine, rifampicin, phenytoin, preparations of St. John's wort perforated - with simultaneous intake reduce the concentration of sirolimus in the blood.
When used simultaneously with fibrates and with HMG-CoA reductase inhibitors, it is recommended that symptoms of rhabdomyolysis be detected in a timely manner.
Special instructions:In order to avoid fluctuations in the concentration of the drug in the blood, it is recommended to take sirolimus at the same time - 4 hours after the administration of cyclosporine.
Immunosuppression contributes to increased susceptibility to infections, therefore, when applying sirolimus, antimicrobial prophylaxis is recommended for 1 year after transplantation.