Atgam - instructions for use, analogs, reviews and release forms (injections in ampoules for injections 5 ml) of a drug for the treatment and prevention of kidney transplant rejection, aplastic anemia, in adults, children and in pregnancy

In this article, you can read the instructions for using the drug Atgam. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Atgam in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Atgam in the presence of existing structural analogues.Use to treat and prevent rejection of kidney transplant, aplastic anemia in adults, children, as well as during pregnancy and lactation.

Atgam - immunosuppressive drug. It is a selective immunosuppressant, which reduces the number of circulating thymus-dependent lymphocytes that form rosettes with erythrocytes of a ram. It is believed that this antilymphocytic action reflects a change in the function of T-lymphocytes responsible for cellular immunity and participating in the humoral immune response. In addition to anti-lymphocyte activity, Atgam contains a small concentration of antibodies against other blood elements. In the monkeys rhesus and cynomolgus, it reduces the number of lymphocytes in the thymus-dependent zones of the spleen and lymph nodes. When the drug is prescribed together with other immunosuppressive agents, such as antimetabolites and glucocorticosteroids (GCS), the formation of antibodies to the gamma globulin of the horse in a patient is insignificant.

Composition

Immunoglobulin antitimotsitarny (horse) + auxiliary substances.

Pharmacokinetics

With the appointment of Atgam in combination with other immunosuppressive agents, the half-life of equine immunoglobulin G (IgG) in plasma is 5.7 plus or minus 3 days.

Indications

• to prevent rejection of transplant rejection during kidney transplantation (when appointed concomitantly with conventional therapy increases the frequency of favorable outcomes during the rejection period);
• to delay the first episode of the transplant rejection reaction in kidney transplantation (as an addition to other methods of immunosuppressive therapy);
• treatment of aplastic anemia in the absence of indications for bone marrow transplantation (when prescribed in addition to standard maintenance therapy, Atgam can cause complete or partial hematologic remission, improvement of survival in cases of proven or suspected immune etiology of the disease).

To date, the effectiveness and safety of the drug in other cases, except kidney transplantation and aplastic anemia, has not been evaluated.

Forms of release

Concentrate for the preparation of a solution for infusions in ampoules 5 ml (injections in ampoules for injections).

Instructions for use and dosing regimen

Atgam is intended only for intravenous administration.

The drug is not suitable for use in ampoules with broken integrity, lack of marking, when physical properties change (color change,presence of foreign particles), expired shelf life, improper storage.

Breeding instructions

For intravenous infusion, the daily dose of Atgam is added to the dilution solution in accordance with aseptic rules. The concentration should not exceed 4 mg per ml. Stir the solution by gently rocking or rotating the bottle. The drug (diluted or undiluted) should not be shaken, as the foaming and / or denaturation of the protein may occur.

The resulting solution retains its physical and chemical stability for up to 24 hours using the following solvents: sodium chloride solution for injection; injection solution containing 5% Dextrose and 0.225% sodium chloride; solution for injection containing 5% dextrose and 0.45% sodium chloride.

Addition of Atgam to a solution of dextrose for injection is not recommended, since a low salt concentration can cause the formation of a precipitate. Solutions for infusion with a pronounced acidic reaction of the medium can also lead after some time to physical instability. If the Atgham solution can not be used immediately after dilution, it is recommended to store it in the refrigerator, while the total storage time of the solution should not exceed 24 hours, including the infusion time.Before administration, dilute the drug should be heated to room temperature.

Skin tests

To identify patients at high risk of developing an anaphylactic reaction, skin tests are necessary before starting therapy. Within traditional conservative approach is primarily recommended to perform epicutaneous testing (sample prick) on the inner side of the forearm, departing at 5 cm from the wrist joint, an injection is carried into the skin to a depth of 1-1.5 mm after a drop of undiluted formulation. For this purpose, injection needles for intradermal injections having a depth gauge or lancet for obtaining capillary blood, as well as special prick-lancets.

If there is no formation of papules or blister 20 minutes after impaling the skin should be continued by intradermal injection testing: skin flexor surface of the forearm or back was treated with 70% alcohol, then tuberculin syringe or an insulin administered 0.02 ml Atgama diluted 0.9 % sodium chloride solution for injection at a concentration of 1:. 1000 (by volume) with simultaneous control injection of 0.9% sodium chloride solution for injection in the same amount at a distance of 5 cm Evaluation of the results produced after 20 min t.

The formation of a blister at the injection site of Atgam with a diameter exceeding by 3 mm or more the diameter of the blister at the site of the control injection with 0.9% sodium chloride solution, as well as the positive cutaneous test indicate an increased sensitivity to the drug and the probability of developing a systemic allergic reaction with intravenous administration of the drug .

The sensitivity and specificity of this test are not clinically proven. Allergic reactions, such as anaphylactic shock, also occurred in patients with negative skin tests. In the case of a positive local reaction to Atgam, alternative treatment should be considered.

The potential benefits of using the drug and the potential risks should be carefully weighed. If, in the presence of a positive skin test, a decision is made to perform Atgam therapy, treatment should be carried out under conditions that ensure the intensive treatment of allergic reactions of immediate type. Systemic reactions, such as generalized rash, tachycardia, dyspnoea, arterial hypotension or anaphylaxis, exclude further use of Atgam.

Administration of the drug

The preparation may contain granular or flaky inclusions. To prevent them from entering the bloodstream, the injection should always be carried out (regardless of their presence) through the infusion system through a filter with a pore diameter of 0.2 to 1.0 microns. The most convenient place of administration is an arteriovenous anastomosis or shunt, or a central vein with a high blood flow velocity. The introduction of a vein with a high blood flow velocity minimizes the possibility of developing phlebitis and thrombosis. The duration of administration of Atgam dose should not be less than 4 hours. During the infusion of the drug near the patient's bed, you should always have the necessary reanimation equipment. You should constantly monitor the patient for possible allergic reactions during the infusion.

Recipients of renal transplants

Delay of graft rejection: the recommended dose of the drug is from 10 to 15 mg per 1 kg of body weight per day every day for 14 days, then every other day for 14 days. Total 21 doses for 28 days. The first dose is administered no earlier than 24 hours before or no later than 24 hours after transplantation.

Treatment of transplant rejection: the introduction of the first dose with the appearance of signs of a first attack of rejection.In the future, the drug can be administered every other day until the total number of doses is equal to 21.

Usually Atgam is used in combination with azathioprine and GCS, which are most often used to suppress the immune response. With repeated prescriptions of the drug, Atgam should be particularly careful and carefully examine the patient with regard to the symptoms of allergic reactions.

In a small number of studies, a dose of 5 to 25 mg per kg of body weight per day was used in children.

Aplastic anemia

The recommended dose is 10-20 mg per 1 kg of body weight per day daily for 8-14 days. In addition, the drug can be administered every other day for up to 14 days, until the total number of doses is equal to 21. Since atam administration may lead to thrombocytopenia, patients receiving the drug for aplastic anemia may require platelet transfusion.

In controlled studies in patients with aplastic anemia who received Atgam, a statistically significant higher improvement rate was recorded at 3 months compared with standard maintenance treatment.The improvement was characterized by a stable increase in peripheral blood levels and a decrease in the need for blood transfusions.

Side effect

• fever, chills;
• leukopenia, thrombocytopenia, neutropenia, granulocytopenia, aplasia, pancytopenia, hemolysis / hemolytic anemia, anemia, eosinophilia;
• rash, urticaria, angioedema;
• diffuse redness of the skin, itching;
• arthralgia (joint pain);
• a slight increase in liver function tests (ALT - ALT, AST - AST, alkaline phosphatase - AP) and kidney (serum creatinine); Clinical and laboratory (including leukopenia with relative lymphocytosis, decreased erythrocyte sedimentation rate - ESR, albuminuria - protein albumin in the urine) symptoms of serum sickness;
• headache;
• nausea, vomiting;
• diarrhea;
• dyspnoea (dyspnea);
• hypotension (low blood pressure);
• night sweats;
• angina;
• stomatitis (inflammation of the oral mucosa);
• pain in the chest, back;
• pain in the injection site;
• thrombosis of the arteriovenous shunt;
• peripheral thrombophlebitis (inflammation of the walls of the veins with the formation of thrombi);
• agitation, lethargy or weakness;
• confusion of consciousness;
• disorientation, movement coordination disorders;
• dizziness;
• malaise;
• pain in the epigastrium (under the sternum) or hiccough;
• gastrointestinal bleeding;
• laryngospasm (spasm of the larynx muscles);
• cough;
• laryngeal edema;
• paresthesia (a sensitivity disorder characterized by sensations of numbness, tingling sensations, crawling crawling);
• lymphadenopathy (enlarged lymph nodes);
• encephalitis (inflammation of the brain);
• reactivation Herpes simplex;
• divergence of the edges of the wound;
• Hyperglycemia (elevated blood sugar levels);
• arterial hypertension (increase in blood pressure);
• pulmonary edema;
• bilateral exudative pleurisy (inflammation of the pleura);
• tachycardia (increased heart rate);
• convulsions;
• anaphylactic reaction;
• obstruction of the iliac veins;
• thrombosis of the renal arteries;
• proteinuria (protein in the urine);
• toxic epidermal necrolysis;
• Decompensated heart failure;
• deep vein thrombosis;
• vasculitis (immunopathological inflammation of blood vessels);
• nose bleed;
• acute renal insufficiency;
• enlargement / rupture of the kidney.

Contraindications

• hypersensitivity to the components of the drug;
• increased sensitivity to other preparations of horse serum.

Application in pregnancy and lactation

Atgam was not used in pregnant women or in lactating women. The effect of the drug on fetal development is not established. It is not known whether it is excreted in breast milk.

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus. In nursing mothers, Atgam should be used with great care.

Use in children

Atgam was safely used in pediatrics for kidney transplantation and in patients with aplastic anemia in doses ranging from 5 to 25 mg per 1 kg of body weight per day.

special instructions

The drug is intended for use only in a hospital!

Atgam should be used by physicians with experience in conducting immunosuppressive therapy for kidney transplantation or in patients with aplastic anemia. Patients receiving Atgam should be treated at departments equipped with appropriate laboratory and medical equipment and staffed by qualified personnel.

Treatment with Atgam should be discontinued if one of the following symptoms develops:

• anaphylaxis;
• severe and persistent thrombocytopenia (platelets - below 70,000 / mm3) in patients with kidney transplant;
• severe and persistent leukopenia (leukocytes - below 1000 / μl) in patients with a transplanted kidney.

During treatment, as with the use of drugs obtained from human blood, there is the possibility of transmission of infectious agents.

Because Atgam, as an immunosuppressive drug, is usually used in combination with GCS and antimetabolites, patients should be carefully examined for leukopenia, thrombocytopenia, or concomitant infection. In some studies, there was an increase in the incidence of cytomegalovirus infection in patients treated with Atgam. This risk can be reduced by lowering the doses of other immunosuppressive drugs prescribed with Atgam. In case of infection, immediate treatment should be given. Taking into account the clinical circumstances, the doctor should decide whether or not to continue treatment with Atgam in this case.

With the development of side effects, the following treatment is recommended:

• anaphylaxis (not a frequent but serious complication, can develop at any time of treatment with the drug) - Immediately stop the infusion of the drug, inject 0.3-1.0 ml of epinephrine (adrenaline, 1: 1000) intramuscularly, apply SCS, auxiliary ventilation, carry out other resuscitation measures. Do not resume treatment with Atgam;
• hemolysis (usually determined only in laboratory, clinically expressed manifestations of hemolysis are rare) - it is recommended to transfuse erythrocyte mass, if necessary, intravenously inject mannitol, furosemide, sodium bicarbonate and other infusion solutions. Expressed and unceasing hemolysis requires the abolition of Atgam treatment;
• thrombocytopenia - in patients with transplanted kidney transient, the number of platelets usually returns to the original without stopping treatment with Atgam. Patients with aplastic anemia may need a transfusion of platelet mass;
• respiratory distress syndrome (may be a manifestation of anaphylactoid reaction) - should stop the infusion of the drug. If distress continues, enter epinephrine (adrenaline), GCS, or a combination of these drugs;
• pain in the chest, side, back (may be a manifestation of anaphylaxis or hemolysis) - treatment is carried out as indicated above for hemolysis and anaphylaxis;
• arterial hypotension / collapse (may indicate anaphylaxis) - should stop the infusion of Atgam and, if necessary, stabilize blood pressure with hypertensive medications;
• chills and fever (the most common phenomena) - it is recommended preventive and / or therapeutic use of antihistamines, antipyretics or GCS;
• phlebitis (can be caused by infusion of Atgam into peripheral veins) - infusion solution should be injected into veins with a high blood flow velocity, for example, arteriovenous anastomosis;
• itching and hyperemia of the skin - prescribe antihistamines;
• Symptoms similar to serum sickness - patients with aplastic anemia are prescribed intravenously or intravenously with SCS. Usually these transient symptoms are resolved and long-term complications are not observed. The prophylactic use of GCS can reduce the frequency of these reactions.

Drug Interactions

Since patients receiving Atgam are concomitantly assigned to SCS or other immunosuppressants, a decrease in their dose may reveal some previously hidden reactions to Atgam.In this case, patients who receive Atgam need careful monitoring.

Analogues of the drug Atgam

Structural analogs for the active substance:

• ATG-Fresenius C;
• Antiliphosphine;
• Antilimfolin-Ks;
• Grafalon;
• Timoglobulin.

Analogues for the pharmacological group (immunosuppressants):

• Abaggio;
• Advagraf;
• Azathioprine;
• Actemra;
• Antiliphosphine;
• Arava;
• Arresto;
• Artamine;
• Benlist;
• Bianodine;
• Hydroxychloroquine;
• Gilenia;
• The festival;
• Grafalon;
• Delagil;
• Zenapax;
• Ilaris;
• Immard;
• The Imnovid;
• Imuran;
• Consuprene;
• Xolar;
• Kuprenil;
• Leflish;
• Leflunomide;
• Lefomide;
• MabThera;
• Misept;
• Mayforth;
• The methodical;
• Mycophenolate;
• Necklair;
• Nulogix;
• Orgosporin;
• Orensia;
• Othello;
• Pantograph;
• Plaquenil;
• Prograph;
• Rapamun;
• Raptiva;
• Redesp;
• Restasis;
• Rituximab;
• CellCent;
• Sertikan;
• Simponi;
• Simulect;
• Soliris;
• Suprema;
• Tacrolimus;
• Tacrose;
• Tauredon;
• Teriflunomide;
• Timoglobulin;
• Timodepressin;
• Femoriks;
• Flammages;
• Humirah;
• Cycloral-FS;
• Cyclosporin;
• Ecological;
• Elafra;
• Enbrel;
• Antivio;
• Yaqurinus.

Response of a therapist

In my practice there was only one patient with aplastic anemia,who during the treatment in the hematological hospital repeatedly received courses of intravenous infusions of Atgam in combination with other medicinal preparations. According to the patient, he repeatedly poured a platelet mass, which indicates the development of a side effect in the form of thrombocytopenia. In addition, the patient talked about other adverse reactions during treatment, such as: abdominal pain and joint pain, nausea, night sweats, general malaise. The patient noted that he was discharged from the hospital at the end of therapy with satisfactory parameters of peripheral blood.

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