ATGAM INJECTION 50 MG/ML [SIN01490P]

Product Info

ATGAM INJECTION 50 MG/ML

[SIN01490P]

THERAPEUTIC INDICATIONS

Renal allograft recipients

ATGAM sterile solution is indicated for the management of allograft rejection in renal transplant patients. When administered with conventional therapy at the time of rejection, it increases the frequency of resolution of the acute rejection episode. The drug has also been administered as an adjunct to other immunosuppressive therapy to delay the onset of the first rejection episode. Data accumulated to date have not consistently demonstrated improvement in functional graft survival associated with therapy to delay the onset of the first rejection episode.

Aplastic anemia

ATGAM is indicated for use in adults and in children aged 2 years and older for the treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation.

When administered with a regimen of supportive care, ATGAM may induce partial or complete hematologic remission. In a controlled trial, patients receiving ATGAM showed a statistically significantly higher improvement rate compared with standard supportive care at 3 months. Improvement was defined in terms of sustained increase in peripheral blood counts and reduced transfusion needs.

The usefulness of ATGAM has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi's syndrome, or in patients known to have been exposed to myelotoxic agents or radiation.

To date, safety and efficacy have not been established in circumstances other than renal transplantation and aplastic anemia.

POSOLOGY AND METHOD OF ADMINISTRATION

Posology

Renal allograft rejection treatment and prophylaxis – adult patients

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 25 mg/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.

Do not infuse a dose of ATGAM in less than 4 hours.

Treatment of aplastic anemia – adult patients and children aged 2 years and older

Dosage recommendations are based on body weight (bw).

The recommended total dose of ATGAM is 160 mg/kg bw, administered as part of standard immunosuppressive therapy, as follows:

• 16 mg/kg bw/day over 10 days or

• 20 mg/kg bw/day over 8 days or

• 40 mg/kg bw/day over 4 days

The recommended infusion duration for the 40 mg/kg dose regimen is 12 to 18 hours. Do not infuse a dose of ATGAM in less than 4 hours.

Special populations

Renal and hepatic impairment

Specific clinical studies have not been performed to assess the effect of renal or hepatic impairment on the pharmacokinetics of ATGAM.

Pediatric population

Currently available data in children less than 18 years of age are described in section PHARMACODYNAMIC PROPERTIES – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Elderly population (≥65 years of age)

Renal allograft recipients

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).

Aplastic anemia

Clinical experience in elderly patients has not identified differences in responses between the elderly and younger patients. Therefore, no dose adjustment is recommended for elderly patients.

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.

Any unused product or waste material should be disposed of in accordance with local requirements.

Method of administration

Following dilution, ATGAM is intended for intravenous use and administration via a high-flow central vein is preferred.

Monitor the patient continuously throughout the infusion for possible allergic reactions (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). Always keep appropriate resuscitation equipment at the patient's bedside while ATGAM is being administered.

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 (not supplied) 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 insoluble material that may have developed in the concentrate. The use of high-flow veins will minimize the occurrence of phlebitis and thrombosis.

Infusion volumes of 250 mL to 500 mL may be used. The infusion volume of the diluted solution should take into consideration factors such as patient’s hemodynamic status, age, and weight. Following administration, it is recommended to flush the intravenous line.

Treatment of aplastic anemia - concomitant immunosuppressive therapy and pre-medication

ATGAM is most commonly administered with ciclosporin.

It is recommended to administer pre-medication with corticosteroids and antihistamines prior to infusion of ATGAM in accordance with local treatment guidelines. Anti-pyretics may also increase the tolerability of ATGAM infusion (see UNDESIRABLE EFFECTS – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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.

CONTRAINDICATIONS

Do not administer ATGAM to a patient who has had a severe systemic reaction (e.g., anaphylactic reaction) during prior administration of ATGAM or any other equine gamma globulin preparation.