ATGAM

Active material: Immunoglobulin antitimotsitarnyi
When ATH: L04AA03
CCF: Antitimotsitarnyi immunoglobulin
ICD-10 codes (testimony): D61, Z94
When CSF: 14.02.01
Manufacturer: PHARMACIA & UPJOHN COMPANY (United States)

Pharmaceutical form, composition and packaging

Concentrate for solution for infusion a transparent or slightly opalescent liquid, colorless or pinkish, or brownish; the storage can be formed small granular or flocculent precipitate, does not affect the activity.

Excipients: glycine, water d / and.

5 ml – colorless glass vials (1) – packs cardboard.
5 ml – colorless glass vials (5) – packs cardboard.

Pharmacological action

Immunosuppressive drugs. Atgam^® It is a selective immunosuppressant, reducing the number of circulating thymus-dependent lymphocyte, forming rosettes with sheep red blood cells. It is believed, it antilymphocytic action reflects the change in the function of T-lymphocytes, responsible for cell-mediated immunity, and involved in the humoral immune response. In addition to the activity antilymphocytic Atgam^® It contains a small concentration of antibodies against other blood corpuscles. In monkeys, rhesus and cynomolgus Atgam^® It reduces the number of lymphocytes in the thymus-dependent areas of spleen and lymph nodes. When administering the drug in conjunction with other immunosuppressive agents, such as corticosteroids and antimetabolites, education of the patient antibodies to gamma globulin horse not much.

Pharmacokinetics

In appointing Atgama^® in combination with other immunosuppressive agents equine IgG half-life in plasma was 5.7 ± 3 days.

Testimony

- For the prevention of graft rejection in the kidney transplant (the appointment along with conventional therapy increases the incidence of favorable outcomes during the period of exclusion);

- To delay the first episode of graft rejection in the kidney transplant (as a complement to other methods of immunosuppressive therapy);

- Treatment of aplastic anemia in the absence of indications for bone marrow transplant (when given in addition to standard maintenance therapy Atgam^® can cause complete or partial remission, improved survival in cases of proven or suspected immune etiology).

To date, the efficacy and safety of the drug in other cases, except kidney transplant and aplastic anemia, not yet rated.

Dosage regimen

Atgam^® It is designed for on / in the.

Not suitable for use in drug vials with impaired integrity, lack of labeling, when changing the physical properties of (discoloration, the presence of foreign particles), if expired, improper storage.

Instructions for breeding

For in / infusion daily dose Atgama^® added to the solution to dilute aseptically. The concentration should not exceed 4 mg / ml. Stir the solution, gently shaking or rotating the bottle. Preparation (the diluted or undiluted) not to be shaken, as foaming may occur, and / or denaturation of the protein.

The resulting solution preserves the physical and chemical stability to 24 hours, using the following solvents: Sodium Chloride Injection; injection, comprising 5% dextrose 0.225% sodium chloride; injection, comprising 5% dextrose 0.45% sodium chloride.

Adding Atgama^® to a solution of dextrose for injection is not recommended, because low salt concentrations can cause precipitation. Infusion solutions with a strong acidic environment can also lead over time to physical instability. If the solution Atgama^® can not be used immediately after dilution, it should be stored in the refrigerator, wherein the total storage time the solution should not exceed 24 no (including infusion time). Before the introduction of the dilution should be warmed to room temperature.

Skin tests

In order to identify patients at high risk of developing 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 (sample nakalыvaniem): on the inner side of the forearm, otstupiv of 5 cm from the wrist, It carried out an injection into the skin to a depth of 1-1.5 mm after a drop of undiluted preparation. For this, the injection needle to / for injections, with the depth, or lancet to obtain capillary blood, as well as special prick-lancet.

If after 20 minutes after impaling the skin does not form a papule or blister, We should continue testing by / c injection: the skin surface of the forearm flexion, or on the back handle 70% alcohol, whereupon tuberculin syringe or an insulin administered 0.02 ml Atgama^®, diluted 0.9% solution of sodium chloride for injections at a concentration 1:1000 (in terms of volume) control simultaneous injection 0.9% solution of sodium chloride for injections to the same extent in the region 5 cm. Evaluation of the results is made through 20 m.

Education at the injection site Atgama^® Blister diameter, higher than in the 3 mm and a diameter at the place of the blister control injections 0.9% sodium chloride solution, as well as a positive cutaneous test show hypersensitivity to the drug and the likelihood of systemic allergic reactions at / in the introduction of the drug.

The sensitivity and specificity of this test is not clinically proven. Allergic reactions, such as anaphylactic shock, occurs in patients with negative skin tests. In case of positive response to the local Atgam^® should consider alternative treatment.

The potential benefits of the drug and possible risks should be carefully weighed. If there is a positive skin test decided to conduct therapy Atgamom^®, treatment should be carried out under, providing intensive care allergic immediate type. Systemic reactions, such as generalized rash, tachycardia, dyspnoea, hypotension and anaphylaxis exclude further application Atgama^®.

The introduction of the drug

The drug may contain granular or flaky inclusion. In order to prevent their falling into the bloodstream administration always (regardless of their presence) It should be carried out by the infusion system through a filter with a pore diameter of 0.2 to 1.0 micron. The most convenient place of administration is arterio-venous anastomosis or shunt, or central Vienna high velocity flow. Introduction into the vein at a high rate of blood flow minimizes the possibility of phlebitis and thrombosis. The duration of dosing Atgama^® should be at least 4 no. During the infusion the patient's bedside, always have the necessary resuscitation equipment. It should constantly monitor the patient for possible allergic reactions during infusion.

Kidney transplant recipients

Delayed graft rejection: the recommended dose – from 10 to 15 mg / kg / day daily for 14 days, then every other day for 14 days. Total 21 dose for 28 days. The first dose administered no earlier than 24 hours before or no later 24 hours after transplantation.

Treatment of transplant rejection: the first dose when the signs first episode of rejection. Subsequently, the drug may be administered every other day until the total number of doses, equal 21.

Usually Atgam^® used in combination with corticosteroids and azitioprinom, It is most often used to suppress the immune response. Repeated use of the drug Atgam^® It should be especially careful and carefully examine the patient on the symptoms of allergic reactions.

In a few studies, children used dose from 5 to 25 mg / kg / day.

Aplasticheskaya anemia

The recommended dose is 10-20 mg / kg / day daily for 8-14 days. Additionally, the drug may be administered every other day for 14 days until the total number of doses, equal 21. Since the introduction of Atgama^® may develop thrombocytopenia, patients, receiving medication for aplastic anemia, It may require platelet transfusions.

In controlled trials in patients with aplastic anemia, receiving Atgam^®, through 3 month registered a statistically significant higher incidence of improvement over standard maintenance treatment. Improvement was characterized by a steady increase in the peripheral blood and decrease the need for blood transfusions.

Side effect

Basic experience in the use Atgama^® accumulated in patients after kidney transplantation, receiving standard immunosuppressive treatment (azathioprine, GCS). Frequently: fever, chills, leukopenia, thrombocytopenia, rash, hives, diffuse redness of the skin, itch.

The frequency of adverse events was higher in the treatment of aplastic anemia. Often: fever, chills, rash, arthralgia, thrombocytopenia. In patients with aplastic anemia and other hematological diseases, receiving Atgam^®, There was a slight increase in liver function tests (ACT, GOLD, Alkaline phosphatase) and kidney (sыvorotochnыy creatinine). Several studies have been reported and clinical laboratory (incl. leukopenia with relative lymphocytosis, decrease ESR, albuminuria) signs of serum sickness.

In patients with kidney transplantation or aplastic anemia, receiving Atgam^®, registered the following adverse reactions: headache, nausea, vomiting, diarrhea, dyspnoea, gipotenziya, night sweat, stomatitis, chest pain, back, Infusion site, thrombosis arteriovenous shunt, peripheral thrombophlebitis.

Rarely: angioedema, excitation, dizziness, lethargy or weakness, malaise, epigastric pain or hiccups, laringospazm, paresthesia, lymphadenopathy, infection, encephalitis, реактивация Herpes simplex, dehiscence, giperglikemiâ, arterial hypertension, pulmonary edema, bilateral pleural effusion, tachycardia, convulsions, anaphylactic reaction, iliac vein occlusion, renal artery thrombosis, proteinuria, toxic epidermal necrolysis.

Post-marketing studies

During 5 years after receiving the drug on the market rate of reported adverse events was: fever – 51%; chills -16%; thrombocytopenia – 30%; leukopenia -14%; rash – 27%; generalized infection -13%.

IN 5-10% cases were noted: deviations in terms of kidney function; symptoms, similar to serum sickness; dyspnea / apnea; arthralgia; chest pain, by, back; diarrhea; nausea and / or vomiting.

Adverse Reactions, notes with frequency < 5%

Cardio-vascular system: arterial hypertension, hypotension, tachycardia, pulmonary edema, decompensated heart failure, deep vein thrombosis, tromboflebit, vasculitis, renal artery thrombosis, nose bleed.

From the central and peripheral nervous system: headache, weakness, convulsions, paraesthesia, confusion, disorientation, impaired coordination of movements, tremor, dizziness, muscle stiffness, Sweating.

From the digestive system: gastrointestinal bleeding / perforation, epigastric pain, stomach and abdominal, abnormalities in liver function tests.

Metabolism: giperglikemiâ.

From the urinary system: acute renal failure, up / break kidney.

The respiratory system: cough, laringospazm, laryngeal edema, sore throat, stomatitis.

From the hematopoietic system: neutropenia, granulocytopenia, aplasia, pancytopenia, gemoliz / gemoliticheskaya anemia, anemia, eozinofilija, lymphadenopathy.

Other: anaphylaxis, swelling / redness at the site of infusion, infection at the injection site, myalgia / pain in Nogah, viral hepatitis, реактивация Herpes simplex.

Contraindications

- Hypersensitivity to the drug;

- Hypersensitivity to other drugs in horse serum.

Pregnancy and lactation

Atgam^® shall not apply in pregnant, nor in lactating women. Effect on the development of the fetus is not established. It is not known whether it is allocated Atgam^® breast milk .

Use of the drug during pregnancy is possible only in case, when the intended benefits to the mother outweighs the potential risk to the fetus. In nursing mothers Atgam^® should be used with great caution.

Cautions

The drug is intended for use only in a hospital!

Apply Atgam^® should doctors, with experience of immunosuppressive therapy in kidney transplant or in patients with aplastic anemia. Patients, receiving Atgam^®, must be treated in offices, equipped with appropriate laboratory and medical equipment and staffed by qualified personnel.

Treatment Atgamom^® discontinue, develops if one of the following symptoms:

1. Anaphylaxis.

2. Severe and persistent thrombocytopenia (platelets – below 70 000/l) in patients with kidney transplant.

3. Severe and persistent leukopenia (leukocytes – below 1000 / mm) in patients with kidney transplant.

Same, as in the use of drugs, derived from human blood, there is a possibility of transmission of infectious agents.

Since Atgam^®, as an immunosuppressive drug, It is typically used in combination with corticosteroids, and antimetabolites, Patients should be carefully examined with respect to leukopenia, thrombocytopenia, or concurrent infection. Some studies have noted an increase in the incidence of CMV infection in patients, receiving Atgam^®. This risk can be reduced by lowering the dose of other immunosuppressive drugs, appointed with Atgamom^®. In the event of the accession of infection should be immediately appropriate treatment. Taking into account the clinical circumstances, the doctor should decide, whether it is necessary in this case to continue treatment Atgamom^®.

With the development of side effects is recommended following treatment

1. Anaphylaxis (not frequent, but serious complication, It can develop at any time of treatment) – should immediately stop the infusion of the drug, enter / m 0.3 – 1.0 ml epinephrine (adrenaline; 1:1000), use of GCS, auxiliary ventilation, conduct other resuscitation. Do not renew the treatment Atgamom^®.

2. Gemoliz (usually determined by a laboratory, symptomatic manifestations of hemolysis are rare) – recommended red blood cell transfusions, if appropriate in / injected mannitol, furosemid, sodium bicarbonate and other infusion solutions. Expression and ongoing hemolysis require discontinuation Atgamom^®.

3. Thrombocytopenia – in patients with transplanted kidney transient, platelet count usually returns to baseline without discontinuation of treatment Atgamom^®. Patients with aplastic anemia may need transfusions of platelets.

4. Respiratory Distress Syndrome (It may be a manifestation of anaphylactoid reactions) – should stop drug infusion. If distress continues, enter epinephrine (adrenaline), Corticosteroids or a combination of these drugs.

5. Chest pain, by, back (It may be a manifestation of anaphylaxis or hemolysis) – treatment is carried out, as described above for the hemolysis and anaphylaxis.

6. Hypotension / collapse (may indicate anaphylaxis) – discontinue infusion Atgama^® and if necessary to stabilize the blood pressure of hypertensive drugs.

7. Chills and fever (common phenomenon) – recommended preventive and / or therapeutic use of antihistamines, antipyretics, or corticosteroids.

8. Phlebitis (It can be caused by infusion Atgama^® a peripheral vein) – infusion solution should be injected into veins with a high flow rate, eg, Hoyer's canal.

9. Itching and redness of the skin – prescribe antihistamines.

10. Symptoms, similar to serum sickness, – patients with aplastic anemia appointed interior or / SCS. Usually these symptoms are transient and resolved long-term complications are not observed. Prophylactic corticosteroids may reduce the incidence of these reactions.

Use in Pediatrics

Atgam^® safely used in pediatric kidney transplantation in patients with aplastic anemia at doses, comparable with those for adults.

Overdose

The expected maximum tolerated dose Atgam^® It is an individual. To date, the largest single daily dose, used in patients with transplanted kidney, made 7 g introduction concentration 10 mg / ml in sodium chloride solution for injection, while the symptoms of acute intoxication were not observed. The largest number of doses (from 10 to 20 mg / kg / day), which may be administered to the patient, not yet defined. Some patients after kidney transplantation was introduced to 50 doses within 4 months, others received 28-day course of 21 dose, for the treatment of acute rejection was required three or more courses of treatment. The number of cases of toxic manifestations under one of the schemes used did not increase.

Drug Interactions

Since patients, Gets Atgam^®, at the same time prescribe corticosteroids or other immunosuppressive drugs, while reducing their dose may exhibit some previously hidden reactions to Atgam^®. In this case the patient, receiving Atgam^®, should be closely monitored.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored and transported at a temperature of from 2 ° to 8 ° C in the dark, reach of children; Do not freeze. Shelf life – 3 year. Do not use beyond the expiration date.