Release form, composition and packing
Concentrate for solution for infusion in the form of a transparent or slightly opalescent liquid, colorless or with a pinkish or brownish tint in storage can be formed small granular or flocculent precipitate, not affecting the activity.
1 ml 1 amp. antithymocyte immunoglobulin (horse) 50 mg 250 mg.
Other ingredients: glycine, water q / and. Clinico-pharmacological group: antithymocyte immunoglobulin.
Pharmacological action
Immunosuppressive drug. Atgam is a selective immunosuppressive agent that reduces the number of circulating thymusdependent lymphocytes forming rosettes with sheep red blood cells.
It is believed that this antilymphocytic action reflects the change of T-lymphocytes responsible for cellular immunity and are involved in humoral immune response. In addition to antilymphocytic activity Atgam contains a low concentration of antibodies against other blood cells.
In monkeys, rhesus and cynomolgus Atgam reduces the number of lymphocytes in thymusdependent zones of the spleen and lymph nodes.
In the appointment of the drug along with other immunosuppressive agents, such as antimetabolites and corticosteroids, the formation of patient antibodies to gamma-globulin horse is not much. Pharmacokinetics: When assigning Atgama in combination with other immunosuppressive drug half-life of IgG in equine plasma was 5.7 ± 3 days.
Statement
for the prevention of graft rejection reactions in kidney transplants (for appointment along with conventional therapy increases the frequency of favorable outcomes during the period of exclusion);
to delay the first episode of the reaction of graft rejection in kidney transplant (as an adjunct to other methods of immunosuppressive therapy);
treatment of aplastic anemia in the absence of indications for bone marrow transplantation (assignment in addition to standard maintenance therapy Atgam can cause complete or partial hematological remission, improved survival in cases of proven or suspected etiology of immune diseases).
To date, the efficacy and safety in other cases, except for kidney transplants and aplastic anemia, has not been evaluated.
Dosing regimen
Atgam is intended only for iv administration. Not suitable for use in drug vials with violating the integrity, the absence of labeling, a change in physical properties (color change, the presence of foreign particles), and expired, improperly stored.
Notes on the breeding
For IV infusion daily dose Atgama added to a solution for dilution under aseptic conditions. Concentration should not exceed 4 mg / ml. Stirred solution and gently shaking or swirling the bottle. The drug (diluted or undiluted) should not be shaken because it can happen foaming and / or denaturation of the protein.
The resulting solution preserves the physical and chemical stability up to 24 hours when using the following solvents: sodium chloride injection, solution for injection containing 5% dextrose and 0.225% sodium chloride, injectable solution containing 5% dextrose and 0.45% sodium chloride. Adding Atgama to a solution of dextrose injection is not recommended, as low salt concentration can cause the formation of sludge.
Solutions for infusion with a strong acid reaction medium can also lead over time to physical instability. If the solution Atgama not be used immediately after mixing, it is recommended to store in the refrigerator, with a total storage time of the solution should not exceed 24 hours (including infusion time).
Before the introduction of diluted product should be heated to room temperature.
Skin tests
To identify patients at high risk for an anaphylactic reaction before treatment is necessary to conduct skin tests. As part of the conservative traditional approach is primarily recommended to carry out cutaneous test (test with nakalyvaniem): on the inside of the forearm, departing at 5 cm from the wrist, carried out an injection into the skin to a depth of 1-1.5 mm by a drop of undiluted drug.
To do this, use a needle for IV infusions to having a depth gauge, or a lancet to obtain capillary blood, as well as special prick-lancets. If after 20 minutes after nakalyvaniya skin is no formation of pimples or blister, it should continue testing through the w / c injection: the skin surface of the forearm or flexion at the back was treated with 70% alcohol, after which the tuberculin or insulin syringes injected 0.02 ml Atgama diluted 0.9% solution sodium chloride for injection in a concentration of 1:1000 (by volume) with simultaneous control injection of 0.9% sodium chloride solution for injection in the same volume at a distance of 5 cm Evaluation done in 20 minutes.
Education at the injection site Atgama blister diameter greater than 3 mm or more in diameter blister spot control injections with 0.9% sodium chloride solution, and a positive skin test showed high sensitivity to the drug and the likelihood of developing systemic allergic reaction with / in the introduction of the drug . The sensitivity and specificity of this test is not clinically proven.
Allergic reactions such as anaphylactic shock, occurred in patients with negative skin test. In the case of a positive local reaction to Atgam should consider alternative treatments.
Potential benefits of the drug and the potential risk must be carefully weighed.
If you have a positive skin test, decided to hold Atgamom therapy, treatment should be carried out in conditions providing for the holding of intensive therapy of allergic immediate type. Systemic reactions such as generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis preclude further application Atgama.
Infusion
The drug may contain granuloobraznye or flocculating inclusion. To prevent getting into the bloodstream introduction always (regardless of their availability) should be carried out by an infusion system through a filter with a pore diameter of 0.2 to 1.0 microns. The most convenient place for the introduction of an arterio-venous anastomosis or shunt, or central Vienna at a high rate of blood flow. Introduction to the vein at a high rate of blood flow to minimize the possibility of phlebitis and thrombosis.
Duration of dosing Atgama must be at least 4 h. During the infusion of the drug near the patient's bed should always have the necessary resuscitation equipment. Should constantly observe the patient for possible allergic reactions during infusion.
Kidney transplant recipients Delayed graft rejection: the recommended dose - 10 to 15 mg / kg / day daily for 14 days, then every other day for 14 days. Only 21 doses for 28 days. The first dose administered no earlier than 24 hours before or no later than 24 hours after transplantation.
Treatment of transplant rejection: first dose at the signs of the first attack of rejection.
In what the drug can be administered every other day until the total dose of 21. Atgam usually used in conjunction with azitioprinom and corticosteroids, which are most often used to suppress the immune response. If reassignment of the drug Atgam should be especially careful and thoroughly examined the patient for symptoms of allergic reactions. In the few studies in children used a dose of 5 to 25 mg / kg / day.
Aplastic anemia
The recommended dose is 10-20 mg / kg / day daily for 8-14 days. Additionally, the drug can be administered every other day for 14 days to reach the total dose of 21.
Since the introduction of Atgama may develop thrombocytopenia, patients receiving the drug on the aplastic anemia may require transfusion of platelets. In controlled studies in patients with aplastic anemia treated with Atgam, 3 months registered a statistically significant higher rates of improvement compared with standard supportive care.
Improvement was characterized by a steady increase in the peripheral blood and decrease the need for blood transfusions.
Side effect
The basic experience of using Atgama accumulated in patients after kidney transplant, receiving standard immunosuppressive therapy (azathioprine, corticosteroids). The most frequently reported: fever, chills, leukopenia, thrombocytopenia, rash, urticaria, diffuse redness, itching. The frequency of adverse events was higher in the treatment of aplastic anemia.
Frequently reported fever, chills, rash, arthralgia, thrombocytopenia. Patients with aplastic anemia and other hematologic diseases treated with Atgam, it was noted a slight increase in liver function tests (ACT, ALT, ALP) and renal (serum creatinine). Some studies have reported clinical and laboratory (including leukopenia with relative lymphocytosis, lower ESR, albuminuria) signs of serum sickness.
In patients with transplanted kidney or aplastic anemia who received Atgam, reported the following side effects: headache, nausea, vomiting, diarrhea, dyspnea, hypotension, night sweats, stomatitis, chest pain, back pain, the infusion site, thrombosing arteriovenous shunt, peripheral thrombophlebitis.
Rarely observed: angioedema, anxiety, dizziness, lethargy or weakness, malaise, epigastric pain or hiccup, laryngeal spasm, paresthesia, lymphadenopathy, infection, encephalitis, reactivation of Herpes simplex, dehiscence, hyperglycemia, hypertension, pulmonary edema, bilateral pleural pleurisy, tachycardia, seizures, anaphylactic reaction, occlusion of iliac veins, renal artery thrombosis, proteinuria, toxic epidermal necrolysis.
Postmarketing studies
Within 5 years after receiving the drug on the market, the frequency of reported adverse reactions were as follows: fever - 51% -16% chills, thrombocytopenia - 30% -14% leukopenia, rash - 27% -13% generalized infection. In 5-10% of cases were noted: variations in rates of renal function, symptoms similar to serum sickness, dyspnea / apnea, arthralgia, pain in the chest, side, back pain, diarrhea, nausea and / or vomiting.
Concentrate for solution for infusion in the form of a transparent or slightly opalescent liquid, colorless or with a pinkish or brownish tint in storage can be formed small granular or flocculent precipitate, not affecting the activity.
1 ml 1 amp. antithymocyte immunoglobulin (horse) 50 mg 250 mg.
Other ingredients: glycine, water q / and. Clinico-pharmacological group: antithymocyte immunoglobulin.
Pharmacological action
Immunosuppressive drug. Atgam is a selective immunosuppressive agent that reduces the number of circulating thymusdependent lymphocytes forming rosettes with sheep red blood cells.
It is believed that this antilymphocytic action reflects the change of T-lymphocytes responsible for cellular immunity and are involved in humoral immune response. In addition to antilymphocytic activity Atgam contains a low concentration of antibodies against other blood cells.
In monkeys, rhesus and cynomolgus Atgam reduces the number of lymphocytes in thymusdependent zones of the spleen and lymph nodes.
In the appointment of the drug along with other immunosuppressive agents, such as antimetabolites and corticosteroids, the formation of patient antibodies to gamma-globulin horse is not much. Pharmacokinetics: When assigning Atgama in combination with other immunosuppressive drug half-life of IgG in equine plasma was 5.7 ± 3 days.
Statement
for the prevention of graft rejection reactions in kidney transplants (for appointment along with conventional therapy increases the frequency of favorable outcomes during the period of exclusion);
to delay the first episode of the reaction of graft rejection in kidney transplant (as an adjunct to other methods of immunosuppressive therapy);
treatment of aplastic anemia in the absence of indications for bone marrow transplantation (assignment in addition to standard maintenance therapy Atgam can cause complete or partial hematological remission, improved survival in cases of proven or suspected etiology of immune diseases).
To date, the efficacy and safety in other cases, except for kidney transplants and aplastic anemia, has not been evaluated.
Dosing regimen
Atgam is intended only for iv administration. Not suitable for use in drug vials with violating the integrity, the absence of labeling, a change in physical properties (color change, the presence of foreign particles), and expired, improperly stored.
Notes on the breeding
For IV infusion daily dose Atgama added to a solution for dilution under aseptic conditions. Concentration should not exceed 4 mg / ml. Stirred solution and gently shaking or swirling the bottle. The drug (diluted or undiluted) should not be shaken because it can happen foaming and / or denaturation of the protein.
The resulting solution preserves the physical and chemical stability up to 24 hours when using the following solvents: sodium chloride injection, solution for injection containing 5% dextrose and 0.225% sodium chloride, injectable solution containing 5% dextrose and 0.45% sodium chloride. Adding Atgama to a solution of dextrose injection is not recommended, as low salt concentration can cause the formation of sludge.
Solutions for infusion with a strong acid reaction medium can also lead over time to physical instability. If the solution Atgama not be used immediately after mixing, it is recommended to store in the refrigerator, with a total storage time of the solution should not exceed 24 hours (including infusion time).
Before the introduction of diluted product should be heated to room temperature.
Skin tests
To identify patients at high risk for an anaphylactic reaction before treatment is necessary to conduct skin tests. As part of the conservative traditional approach is primarily recommended to carry out cutaneous test (test with nakalyvaniem): on the inside of the forearm, departing at 5 cm from the wrist, carried out an injection into the skin to a depth of 1-1.5 mm by a drop of undiluted drug.
To do this, use a needle for IV infusions to having a depth gauge, or a lancet to obtain capillary blood, as well as special prick-lancets. If after 20 minutes after nakalyvaniya skin is no formation of pimples or blister, it should continue testing through the w / c injection: the skin surface of the forearm or flexion at the back was treated with 70% alcohol, after which the tuberculin or insulin syringes injected 0.02 ml Atgama diluted 0.9% solution sodium chloride for injection in a concentration of 1:1000 (by volume) with simultaneous control injection of 0.9% sodium chloride solution for injection in the same volume at a distance of 5 cm Evaluation done in 20 minutes.
Education at the injection site Atgama blister diameter greater than 3 mm or more in diameter blister spot control injections with 0.9% sodium chloride solution, and a positive skin test showed high sensitivity to the drug and the likelihood of developing systemic allergic reaction with / in the introduction of the drug . The sensitivity and specificity of this test is not clinically proven.
Allergic reactions such as anaphylactic shock, occurred in patients with negative skin test. In the case of a positive local reaction to Atgam should consider alternative treatments.
Potential benefits of the drug and the potential risk must be carefully weighed.
If you have a positive skin test, decided to hold Atgamom therapy, treatment should be carried out in conditions providing for the holding of intensive therapy of allergic immediate type. Systemic reactions such as generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis preclude further application Atgama.
Infusion
The drug may contain granuloobraznye or flocculating inclusion. To prevent getting into the bloodstream introduction always (regardless of their availability) should be carried out by an infusion system through a filter with a pore diameter of 0.2 to 1.0 microns. The most convenient place for the introduction of an arterio-venous anastomosis or shunt, or central Vienna at a high rate of blood flow. Introduction to the vein at a high rate of blood flow to minimize the possibility of phlebitis and thrombosis.
Duration of dosing Atgama must be at least 4 h. During the infusion of the drug near the patient's bed should always have the necessary resuscitation equipment. Should constantly observe the patient for possible allergic reactions during infusion.
Kidney transplant recipients Delayed graft rejection: the recommended dose - 10 to 15 mg / kg / day daily for 14 days, then every other day for 14 days. Only 21 doses for 28 days. The first dose administered no earlier than 24 hours before or no later than 24 hours after transplantation.
Treatment of transplant rejection: first dose at the signs of the first attack of rejection.
In what the drug can be administered every other day until the total dose of 21. Atgam usually used in conjunction with azitioprinom and corticosteroids, which are most often used to suppress the immune response. If reassignment of the drug Atgam should be especially careful and thoroughly examined the patient for symptoms of allergic reactions. In the few studies in children used a dose of 5 to 25 mg / kg / day.
Aplastic anemia
The recommended dose is 10-20 mg / kg / day daily for 8-14 days. Additionally, the drug can be administered every other day for 14 days to reach the total dose of 21.
Since the introduction of Atgama may develop thrombocytopenia, patients receiving the drug on the aplastic anemia may require transfusion of platelets. In controlled studies in patients with aplastic anemia treated with Atgam, 3 months registered a statistically significant higher rates of improvement compared with standard supportive care.
Improvement was characterized by a steady increase in the peripheral blood and decrease the need for blood transfusions.
Side effect
The basic experience of using Atgama accumulated in patients after kidney transplant, receiving standard immunosuppressive therapy (azathioprine, corticosteroids). The most frequently reported: fever, chills, leukopenia, thrombocytopenia, rash, urticaria, diffuse redness, itching. The frequency of adverse events was higher in the treatment of aplastic anemia.
Frequently reported fever, chills, rash, arthralgia, thrombocytopenia. Patients with aplastic anemia and other hematologic diseases treated with Atgam, it was noted a slight increase in liver function tests (ACT, ALT, ALP) and renal (serum creatinine). Some studies have reported clinical and laboratory (including leukopenia with relative lymphocytosis, lower ESR, albuminuria) signs of serum sickness.
In patients with transplanted kidney or aplastic anemia who received Atgam, reported the following side effects: headache, nausea, vomiting, diarrhea, dyspnea, hypotension, night sweats, stomatitis, chest pain, back pain, the infusion site, thrombosing arteriovenous shunt, peripheral thrombophlebitis.
Rarely observed: angioedema, anxiety, dizziness, lethargy or weakness, malaise, epigastric pain or hiccup, laryngeal spasm, paresthesia, lymphadenopathy, infection, encephalitis, reactivation of Herpes simplex, dehiscence, hyperglycemia, hypertension, pulmonary edema, bilateral pleural pleurisy, tachycardia, seizures, anaphylactic reaction, occlusion of iliac veins, renal artery thrombosis, proteinuria, toxic epidermal necrolysis.
Postmarketing studies
Within 5 years after receiving the drug on the market, the frequency of reported adverse reactions were as follows: fever - 51% -16% chills, thrombocytopenia - 30% -14% leukopenia, rash - 27% -13% generalized infection. In 5-10% of cases were noted: variations in rates of renal function, symptoms similar to serum sickness, dyspnea / apnea, arthralgia, pain in the chest, side, back pain, diarrhea, nausea and / or vomiting.
No comments:
Post a Comment