Lymphocyte Immunoglobulin, Anti-Thymocyte Globulin (Equine) (Atgam)

1. Health Canada Product Monograph — Lymphocyte Immunoglobulin, Anti-Thymocyte Globulin (Equine)

• Atgam is used to reduce T-lymphocyte function in patients undergoing kidney (renal) transplantation, both to help delay the onset of rejection and to treat an active rejection episode alongside standard immunosuppressive therapy.
• Atgam is also used to treat aplastic anemia, a condition in which the bone marrow fails to produce enough blood cells.
• Atgam has also been used, without formal approval for these uses, in other transplant settings such as liver, heart, and bone marrow transplantation.

• Atgam has not been well studied in pregnant women, and its effects on a developing fetus are not fully known.
• Atgam should be used during pregnancy only if the expected benefit to the mother clearly justifies the potential risk to the fetus.
• Women of childbearing potential should use effective contraception during Atgam therapy and for at least 10 weeks after the last dose.

• It is not known whether Atgam passes into breast milk.
• Because many drugs are excreted in breast milk and could affect a nursing infant, a decision should be made whether to stop breastfeeding or stop Atgam, weighing the importance of the drug to the mother.

• Clinical experience in elderly patients (65 years and older) has not shown differences in response compared with younger patients.
• Because older adults more often have reduced kidney, liver, or heart function, or take other medications, the dose for an elderly patient should generally be chosen cautiously, starting at the lower end of the dosing range.

• Experience with Atgam in children is limited, though it has been given safely to a small number of pediatric kidney, liver, and bone marrow transplant recipients and to children with aplastic anemia, generally at doses similar to those used in adults.

• For adults receiving a kidney transplant, Atgam doses of 10 to 30 mg/kg of body weight are given daily; children have generally received 5 to 25 mg/kg daily.
• To help delay the onset of transplant rejection, the recommended regimen is a daily dose for 14 days, then every other day for a total of 21 doses over 28 days, with the first dose given within 24 hours before or after the transplant.
• To treat an active rejection episode, a daily dose is given for 14 days, with additional alternate-day doses possible up to a total of 21 doses.
• For aplastic anemia, Atgam is generally given over 8 to 21 doses, and patients may need preventive platelet transfusions because of the risk of low platelet counts.
• Skin testing with Atgam is strongly recommended before the first infusion to check for the possibility of a serious allergic reaction.
• Each dose must be diluted and infused slowly over at least 4 hours through an in-line filter, under close medical supervision with emergency treatment available at the bedside.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• The maximum tolerated dose of Atgam has not been firmly established, since it is a biologic product and tolerance varies between patients.
• The largest recorded single daily dose given to one patient, several times the usual recommended amount, was not associated with signs of acute toxicity.
• Some patients have received many doses over several months without an increase in toxic effects, though such patients require close ongoing monitoring.

• Chills may occur.
• Fever may occur.
• A drop in white blood cell count (leukopenia) may occur.
• A drop in platelet count (thrombocytopenia) may occur.
• Itching, rash, hives, or a wheal-and-flare skin reaction may occur.
• Joint pain (arthralgia) may occur.
• Headache may occur.
• Nausea, vomiting, or diarrhea may occur.
• Pain at the infusion site or in the chest, flank, or back may occur.
• Night sweats may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Anaphylaxis, a severe, life-threatening allergic reaction, can occur, particularly with intravenous infusion.
• Severe and unremitting low platelet counts (thrombocytopenia) may require stopping treatment.
• Severe and unremitting low white blood cell counts (leukopenia) may require stopping treatment.
• Serum sickness, with rash, joint pain, and fever, can develop, particularly in patients treated for aplastic anemia.
• Hemolysis (breakdown of red blood cells) can occur and rarely may be severe.
• Blood clots, including arteriovenous fistula thrombosis and deep vein thrombosis, have been reported.
• Serious infections, including opportunistic bacterial, fungal, and viral infections such as cytomegalovirus and Epstein-Barr virus reactivation, can occur due to immune suppression.
• Cytokine release syndrome, a potentially fatal inflammatory reaction, may occur.
• Seizures, confusion, or loss of consciousness have been reported rarely.
• Severe skin reactions, including toxic epidermal necrolysis, have been reported rarely.
• Seek urgent medical attention for difficulty breathing, chest pain, signs of a severe allergic reaction, unusual bleeding, or signs of infection such as fever with chills.

• Use with caution and only under the supervision of physicians experienced in immunosuppressive therapy and transplant management.
• Use with caution in patients also receiving corticosteroids and other immunosuppressants, since reducing these other drugs can unmask reactions to Atgam.
• Use with caution during repeat courses of Atgam, monitoring closely for allergic reactions.
• Use with caution in patients with a positive skin test reaction, weighing the risk and benefit carefully.
• Use with caution in patients receiving vaccines, since Atgam may reduce vaccine effectiveness and live vaccines are not recommended during therapy.
• Use with caution in patients at risk of infection, since immunosuppression increases susceptibility to opportunistic infections.
• Use with caution in elderly patients, starting at the lower end of the dosing range.

• Contraindicated in patients with known hypersensitivity to Atgam or to any ingredient in the formulation.
• Contraindicated in patients who have had a severe systemic reaction to Atgam or any other equine gamma globulin product in the past.

• Concomitant use with corticosteroids and antimetabolites such as azathioprine is common practice, but reducing the dose of these drugs may unmask previously hidden reactions to Atgam.
• Live vaccines are not recommended during Atgam therapy, since immune suppression may reduce vaccine effectiveness and increase infection risk.
• No other clinically significant drug-drug interactions have been formally established for Atgam.

• Atgam is given only by intravenous infusion in a healthcare setting, so there is no food-timing consideration for this medication.

• Atgam is administered by a healthcare professional as a slow intravenous infusion, given over at least 4 hours; there is no patient-directed timing relative to meals or time of day.

• Atgam ampoules should be stored in the refrigerator at 2 degrees C to 8 degrees C, protected from light, and never frozen.
• Once diluted for infusion, Atgam should be kept at room temperature and used within 24 hours, including the infusion time.

• Atgam is a powerful immune-suppressing medicine given only in hospital under close medical supervision.
• Report any signs of allergic reaction, fever, chills, unusual bleeding, or infection to your healthcare team right away.
• Skin testing is usually done before your first dose to check for the chance of a severe allergic reaction.
• Regular blood tests will be done during treatment to monitor for changes in blood cell counts and organ function.