Index of drugs

Immunosuppression in transplantology: prevention and treatment of transplant rejection. Prevention of the occurrence of acute and chronic graft-versus-host disease after hematopoietic stem cell transplantation in adults. Treatment of ACUTE, sterile-resistant graft-versus-host disease (GvHD). Treatment of aplastic anemia.

1 vial contains 25 mg of rabbit immunoglobulin against human thymocytes.

Rabbit immunoglobulin against human T lymphocytes is a selective immunosuppressive agent. Probably the basic mechanism of immunosuppressive action is depletion of lymphocytes. It recognizes most of the cells with CD2, CD3, CD4, CD8, CD11a, CD18, CD25, HLA-DR and HLA class I antigens involved in the T cell activation cascade during transplant rejection. T cells are eliminated from the bloodstream by complement-dependent lysis and opsonization dependent on the Fc fragment by means of the monocyte and phagocyte system. In addition to T-cell depletion, the immunoglobulin activates other lymphocyte functions associated with immunosuppressive activity. After the first infusion of the drug at 1.25 mg / kg (in kidney recipients), the concentration of rabbit IgG in the blood is 10-40 μg / ml. T_0,5 is 2-3 days. After 2 months of treatment, the rabbit IgG is detectable in 80% of patients. In 40% of patients, immunization against rabbit IgG is observed. In most cases, immunization develops within the first 15 days of the start of treatment.

Hypersensitivity to rabbit protein or other components of the drug. Acute and chronic infections.

Infusion-related reactions, such as a severe cytokine release syndrome or anaphylactic reaction, have been sporadically reported following the administration of the drug. If an anaphylactic reaction occurs, the infusion should be stopped immediately and appropriate treatment instituted. The decision to reintroduce immunoglobulin against human thymocytes in patients who have experienced anaphylactic reaction in the past after drug administration should be carefully considered. Compliance with the recommended dosage and duration of infusion may reduce the frequency and severity of infusion-related reactions and minimize many acute infusion reactions; premedication is also recommended. During treatment, the patient should be observed for signs of infection; it is recommended to use appropriate prophylaxis of infections. Despite the use of methods for inactivating infectious agents, the transfer of known and unknown pathogens can not be completely ruled out. This also applies to unknown or newly discovered viruses and other pathogens. During treatment, the risk of cancer, including lymphoma or post-transplantation lymphoproliferative disease, should be considered. During and after treatment, the number of white blood cells and platelets should be monitored. If thrombocytopenia and / or leukopenia are not a symptom of the underlying disease or are not related to the disease for which the medicine is being administered, a dose reduction or discontinuation of treatment is suggested: where the platelet count is 50-75 x 10⁹/ l or the number of white blood cells is 2-3 x 10⁹/ l - a dose reduction is recommended; in case of severe thrombocytopenia (<50 x 10⁹/ l) or leukopenia (<2 x 10⁹/ l) - the drug should be discontinued.

Do not use during pregnancy and breastfeeding unless it is strictly necessary.

Infusion reactions may occur as early as the first or second infusions, during a single course of treatment that are manifested by: fever, chills, shortness of breath, nausea or vomiting, diarrhea, hypotension or hypertension, general breakdown, rash, headache. Very rare cases of severe anaphylactic reactions have been reported, which in patients who were not using epinephrine were fatal. Cases associated with infusion resulting from cytokine release syndrome (CRS) have been reported; Severe CRSs have been reported rarely including hypotension, acute respiratory distress syndrome, pulmonary edema, myocardial infarction, tachycardia, and death.Also observed were reactions suggestive of serum sickness, such as: fever, rash, muscle and joint pain (occurred between the 5th and 15th day after the start of treatment); injection site reactions such as: pain, swelling and erythema, superficial thrombophlebitis, deep venous thrombosis; neutropenia, thrombocytopenia (associated with the presence of antibodies inducing cross-reactions, particularly intensified during the first two days of treatment and after its completion); cases of infections (bacterial, fungal, viral and protozoan), recurrence of infections (especially CMV) and sepsis - in rare cases, these infections ended in death. In rare cases, a cancerous process has been observed, including post-transplant lymphoproliferative disease and other lymphomas, and solid tumors have always been associated with the combined use of various immunosuppressive agents.

To be used under close medical supervision in a hospital setting, the patient should be monitored during the infusion. The dosage depends on the indication, the schedule of administration and the concomitant use of other immunosuppressants. The dosage of this drug differs from the dosage of other medicines containing immunoglobulin against thymocytes, because they differ in their type and concentration of protein. Make sure that the prescribed dose is appropriate. Treatment can be discontinued without the need to gradually reduce the dose.Immunosuppression in transplantology. Prevention of transplant rejection: 1-1.5 mg / kg / day for 2-9 days after kidney, pancreatic or liver transplantation, and for 2-5 days after heart transplantation. Treatment of acute transplant rejection: 1.5 mg / kg / day for up to 14 days.Prevention of acute and chronic graft-versus-host disease: a transplantation of 2.5 mg / kg / day from -4 to day -2 or day -1 is recommended when transplanting cells (bone marrow or parent haematopoietic blood cells from peripheral blood) from an incompatible or unrelated covariate in adult patients. .Aplastic anemia: 2.5-3.5 mg / kg / day for 5 days (use of the drug in the treatment of aplastic anemia was not established based on controlled clinical trials).Treatment of acute steroid-resistant graft-versus-host disease: individually, usually 2-5 mg / kg / day for 5 days.
Before administration of the drug should be used premedication (daily doses of antipyretics, intravenous corticosteroids and / or antihistamines). It is given after reconstitution with water for injections and dilution in isotonic (0.9%) saline or 5% glucose. It is given in a slow infusion into a large vein, the total infusion time should not be shorter than 4 h. It is also possible to administer to a peripheral vein; in this case, the simultaneous administration of Heparin and Hydrocortisone in an infusion solution of 0.9% sodium chloride reduces the risk of superficial thrombophlebitis and deep venous thrombosis. Combining the drug as well as heparin and hydrocortisone in a Glucose solution led to the precipitation - do not mix these drugs in one solution. When administering the drug, use a built-in 0.2 μm filter with low protein binding capacity.