ATGAM INJECTION 50 mg/ml

INJECTION

**POSOLOGY AND METHOD OF ADMINISTRATION** Adult patients _Renal allograft recipients_ Adult renal allograft patients have received ATGAM sterile solution at the dosage of 10 to 30 mg/kg of body weight daily. The few children studied received 5 to 25mg/kg daily. ATGAM has been used to delay the onset of the first rejection episode and at the time of the first rejection episode. Most patients who received ATGAM for the treatment of acute rejection had not received it starting at the time of transplantation. Usually, ATGAM is used concomitantly with azathioprine and corticosteroids, which are commonly used to suppress the immune response. Exercise caution during repeat courses of ATGAM; carefully observe patients for signs of allergic reactions. _Delaying the onset of allograft rejection:_ Give a fixed dose of 15 mg/kg daily for 14 days, then every other day for 14 days for a total of 21 doses in 28 days. Administer the first dose within 24 hours before or after the transplant. _Treatment of rejection:_ The first dose of ATGAM can be delayed until the diagnosis of the first rejection episode. The recommended dose is 10 to 15 mg/kg daily for 14 days. Additional alternate day therapy up to a total of 21 doses can be given. _Aplastic anemia_ The recommended dosage regimen is 10 to 20 mg/kg daily for 8 to 14 days. Additional alternate day therapy up to a total of 21 doses can be administered. Because thrombocytopenia can be associated with the administration of ATGAM, patients receiving it for the treatment of aplastic anemia may need prophylactic platelet transfusions to maintain platelets at clinically acceptable levels. Elderly population (≥65 years of age) In general, the dose for an elderly patient should be selected with caution, usually starting at the low end of the dosage range (see SPECIAL WARNINGS AND PRECAUTIONS FOR USE – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Skin testing Before the first infusion of ATGAM, it is strongly recommended that patients be tested with an intradermal injection of 0.02 mL of a 1:1,000 dilution (5 mcg horse IgG) of ATGAM in sodium chloride injection, USP and a contralateral sodium chloride injection control. Use only freshly diluted ATGAM for skin testing. The patient, and specifically the skin test, should be observed every 15 to 20 minutes over the first hour after intradermal injection. A local reaction of 10 mm or greater with a wheal or erythema, or both, with or without pseudopod formation and itching or a marked local swelling should be considered a positive test. The predictive value of this test has not been proven clinically. Allergic reactions such as anaphylaxis have occurred in patients whose skin test is negative. In the presence of a locally positive skin test to ATGAM, serious consideration to alternative forms of therapy should be given. The risk to benefit ratio must be carefully weighed. If therapy with ATGAM is deemed appropriate following a locally positive skin test, treatment should be administered in a setting where intensive life support facilities are immediately available and with a physician familiar with the treatment of potentially life threatening allergic reactions is in attendance. A systemic reaction such as a generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis precludes any additional administration of ATGAM see SPECIAL WARNINGS AND PRECAUTIONS FOR USE and UNDESIRABLE EFFECTS – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. Preparation of solution Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. However, because ATGAM is a gamma globulin product, the ATGAM concentrate and diluted solution are transparent to slightly opalescent, colorless to faintly pink or brown, and may develop a slight granular or flaky deposit during storage. ATGAM (diluted or undiluted) should not be shaken because excessive foaming and/or denaturation of the protein may occur. Dilute ATGAM for intravenous infusion in an inverted bottle of sterile vehicle or bag of sterile vehicle so that the undiluted ATGAM does not contact the air inside. Add the total daily dose of ATGAM to an inverted bottle or bag of one of the following sterile vehicles below (also see Incompatibilities and shelf life). - 0.9 % sodium chloride solution, - Glucose solution/sodium chloride solution: - 50 mg/mL (5%) glucose in 0.45% (4.5 mg/mL) sodium chloride solution - 50 mg/mL (5%) glucose in 0.225% (2.25 mg/mL) sodium chloride solution Due to possible precipitation of ATGAM, it is not recommended to dilute with glucose solution alone (see Incompatibilities and shelf life). The recommended concentration of the diluted ATGAM is 1 mg/mL in the sterile vehicle. The concentration should not exceed 4 mg of ATGAM per mL. The diluted solution should be gently rotated or swirled to effect thorough mixing. Administration Diluted ATGAM should be at room temperature before infusion. ATGAM is appropriately administered into a vascular shunt, arterial venous fistula, or a high-flow central vein through an in-line filter with a pore size of 0.2 to 1.0 micron. The in-line filter should be used with all infusions of ATGAM to prevent the administration of any insoluble material that may develop in the product during storage. The use of high-flow veins will minimize the occurrence of phlebitis and thrombosis. Do not infuse a dose of ATGAM in less than 4 hours. Always keep appropriate resuscitation equipment at the patient’s bedside while ATGAM is being administered. Observe the patient continuously for possible allergic reactions throughout the infusions (see UNDESIRABLE EFFECTS – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Any unused product or waste material should be disposed of in accordance with local requirements. Incompatibilities and shelf life _Drug product_ Refer to outer carton for expiration date. _Diluted solution_ ATGAM, once diluted, has been shown to be physically and chemically stable for up to 24 hours at concentrations of up to 4 mg per mL in the following diluents: 0.9% sodium chloride injection, 5% dextrose and 0.225% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection. Diluted solution should be kept at 20–25°C. The solution should be used within 24 hours (including infusion time). ATGAM must not be mixed with other medicinal products except those mentioned above. From a microbiological point of view, unless the method of opening/dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.