ATGAM Concentrate for solution for infusion Ref.[10752] Active ingredients: Antithymocyte immunoglobulin

ATGAM is intended for intravenous use only.

ATGAM is used with concomitant immunosuppressants. During repeat courses of ATGAM, observe patients for signs of allergic reactions [see Warnings and Precautions (5.1)].

2.1 Dose

Renal Allograft Recipients

Renal transplant rejection: The recommended dose is 10 to 15 mg/kg daily intravenously for 14 days. Additional alternate-day therapy up to a total of 21 doses may be given.

Aplastic Anemia (Moderate to Severe)

The recommended dose is 10 to 20 mg/kg daily intravenously for 8 to 14 days. Additional alternate-day therapy up to a total of 21 doses may be given. 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.

Geriatric population (≥65 years of age): Select the dose for an elderly patient with caution, starting at the low end of the dosage range [see Use in Specific Populations (8.5)].

2.2 Preparation and Administration

Preparation of Solution:

• Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. However, because ATGAM is a gamma globulin product, it can be transparent to slightly opalescent, colorless to faintly pink or brown, and may develop a slight granular or flaky deposit during storage. Do not shake ATGAM (diluted or undiluted) because excessive foaming and/or denaturation of the protein may occur.
• Dilute ATGAM for intravenous infusion in an inverted bottle of sterile vehicle so the undiluted ATGAM does not contact the air inside. Add the total daily dose of ATGAM to the sterile vehicle (see Compatibility and Stability). Do not exceed a concentration of 4 mg of ATGAM per mL. Gently rotate or swirl the diluted solution 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 using an in-line filter with a pore size of 0.2 to 1.0 micron. Use the in-line filter with all infusions of ATGAM to prevent the administration of any insoluble material that may develop in the product during storage. Use high-flow veins to 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 Warnings and Precautions (5.1) and Adverse Reactions (6)].

Compatibility and Stability:

• Once diluted, ATGAM 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.
• Do not dilute ATGAM in Dextrose Injection, USP, as low salt concentrations may cause precipitation. Do not use highly acidic infusion solutions since these solutions may contribute to physical instability over time.
• Store diluted ATGAM at room temperature. The diluted solution must be infused within 24 hours (including infusion time).

The maximum tolerated dose of ATGAM Sterile Solution would be expected to vary from patient to patient due to the biological nature of the product. The largest single daily dose known to be administered to a patient (renal transplant recipient) was 7,000 mg administered at a concentration of approximately 10 mg/mL Sodium Chloride Injection, USP, seven times the recommended total dose and infusion concentration. In this patient, the administration of ATGAM was not associated with any signs of acute intoxication or late sequelae.

A maximum therapeutic dose has not been established therefore the definition of overdose for ATGAM has not been clearly defined. Some renal transplant patients have received up to 50 doses in 4 months, and others have received 28-day courses of 21 doses followed by as many as 3 more courses for the treatment of acute rejection. The incidence of toxicologic manifestations did not increase with any of these regimens; however, close monitoring of the patient is recommended.

Store in a refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE. Store in the original carton to protect from light.

For storage conditions of diluted solution, see Dosage and Administration (2.2).