Anti-thymocyte Globulin (ATGAM®); Anti-thymocyte Globulin (Thymoglobulin®)

Immunosuppressant gamma globulin, primarily monomeric IgG, from hyper immune serum of horses immunized with human thymic lymphocytes

Mechanism of Action
Antibodies of multiple specificities interact with lymphocyte surface antigens, depleting numbers of circulating, thymus-dependent lymphocytes and interfering with cell-mediated humoral immune responses.

Therapeutic Uses
FDA approved: Management of renal allograft rejection; adjunct to other immunosuppressive therapy to delay the onset of the first rejection episode.
Non-FDA: other transplants, rejection of allograft.

Contraindication
Hypersensitivity to ATGAM® or any other equine gamma globulin preparation.

Adverse Drug Events
Hypersensitivity, anaphylaxis; fever, chills, flu-like symptoms, leukopenia, thrombocytopenia, hemolysis, rash (measle like).

Drug-Drug Interactions
Dextrose injection, USP (incompatible with dextrose solutions).

Dosage Forms
Injection, 50mg/ml (5ml ampule).

Dosage and Administration
Usual dose is 10-15 mg/kg/day IV; intradermal test dose prior to administering full dose; infuse for four to eight hours; MUST USE IN LINE FILTER. Dose daily for 10 to 14 days.

Compatibilities/Special Administration Techniques
Administer through high flow central line (or arterial-venous fistula or vascular shunt).

Muromonab-CD3 (Orthoclone®, OKT3)

Immunosuppressive monoclonal antibody with singular specificity to CD3 antigen of human T cells.

Mechanism of Action
Blocks the function of CD3 molecule in the membrane of human T cells, which has been associated in vitro with the antigen recognition structure of human T cells that is essential for signal transduction.

Therapeutic Uses
FDA approved: Treatment of acute allograft rejection as soon as it is diagnosed in kidney transplants; treatment of steroid-resistant acute cardiac allograft rejection; treatment of steroid-resistant acute hepatic allograft rejection.

Contraindications
Hypersensitivity to muromonab-CD3 and/or any product of murine origin, anti-murine antibody titers ≥ 1:1000, uncompensated heart failure or fluid overload, history of seizures, pregnant or breast-feeding.

WARNINGS AND PRECAUTIONS

• Anaphylactic reactions can occur (cardiac/respiratory arrest).
• Cytokine release syndrome, ranging from a mild, self-limited, flu-like syndrome to a less-frequently reported severe, life-threatening shock-like reaction, has been associated with first few doses.
• Neurological events including encephalopathy, seizures, cerebral edema, aseptic meningitis, and headache can occur.

• Patients should be managed in a facility equipped and staffed for cardiopulmonary resuscitation.

Patient Monitoring

• Frequent vital signs, every 15 minutes for the first 2 hours after infusion, including BP, respirations, and HR. Monitor for rash, itching, and palpitations. Monitor serum creatinine, BUN, liver function tests, CBC w/differential.
• Clear chest X-ray and weight restriction of <3% above patients’ minimum weight is required during the week prior to injection. If patients temperature > 37.8 º C should be lowered with antipyretics before each injection.

• Potentially serious signs and symptoms with immediate onset are likely due to hypersensitivity and therapy should be discontinued.

Adverse Events

• pyrexia,
• chills,
• dyspnea,
• N/V, diarrhea
chest pain
• tremor
• wheezing
• headache
• hypersensitivity reactions
• tachycardia
• rigor
• hypertension increased risk of infection

• PTLD.

Drug-Drug Interactions
Indomethacin, corticosteroids, azathioprine, cyclosporine (associated with adverse CNS effects, infection, etc.).

Dosage Forms
Intravenous only, 5mg vial.

Dosage and Administration
usual dose is 5 mg IV bolus, given in less than 1 minute; flush with saline before and after injection; doses given daily for 10 - 14 days.

Compatibilities/Special Administration Techniques
Do not shake; must be refrigerated.

Basiliximab (Simulect®)

Chimeric monoclonal antibody produced by recombinant DNA technology; specifically binds to the alpha subunit of the interleukin-2 (IL-2) receptor of T- and B-lymphocytes.

Mechanism of Action
Binds with high affinity to the alpha subunit of the IL-2 receptor on activated T- and B-lymphocytes and inhibits IL-2 mediated activation of lymphocytes, thus minimizing the cellular immune response that could result in allograft rejection.

Therapeutic Uses
FDA approved for prophylaxis of acute organ rejection in combination with other immunosuppressive agents in patients receiving renal transplants.

Adverse Drug Events
GI complaints (nausea, vomiting, diarrhea, etc.), edema, tremor headache, dizziness, fever, hyper- or hypotension, dyspnea, pulmonary edema, impaired wound healing, musculoskeletal pain, back pain, tachycardia. Cytokine release syndrome does not occur.

Patient Monitoring
Anaphylactoid reactions have been reported; epinephrine should be readily available, particularly during administration of the second Simulect dose; frequent monitoring of routine vitals should be carried out after drug infusion.

Drug-Drug Interactions
None reported.

Dosage Forms
Intravenous only, 20 mg vial (delivered to the floor as an IVPB).

Dosage and Administration
20 mg within 2 hours of transplantation and 20 mg 4 days after transplantation; the reconstituted dose is diluted to a volume of 50 mL with 0.9% sodium chloride or dextrose 5% for infusion; administer via central or peripheral vein over 20 to 30 minutes.

Compatibilities/Special Administration Techniques
DO NOT SHAKE; inspect visually for particulate matter and discoloration before administration – if present, do not use; assure sterility of the prepared solution, since the drug product does not contain any antimicrobial preservative or bacteriostatic agents; prepared infusion must be used within 4 hours, otherwise it may be refrigerated for up to 24 hours.

Daclizumab (Zenapax®)

Humanized monoclonal antibody produced by recombinant DNA technology; specifically binds to the alpha subunit of the interleukin-2 (IL-2) receptor of T- and B-lymphocytes.

Mechanism of Action
Binds with high affinity to the alpha subunit of the IL-2 receptor on activated T- and B-lymphocytes and inhibits IL-2 mediated activation of lymphocytes, thus minimizing the cellular immune response that could result in allograft rejection.

Therapeutic Uses
FDA approved for prophylaxis of acute organ rejection in combination with other immunosuppressive agents in patients receiving renal transplants.

Adverse Drug Events
GI complaints (nausea, vomiting, diarrhea, etc.), edema, tremor headache, dizziness, fever, hyper- or hypotension, dyspnea, pulmonary edema, impaired wound healing, musculoskeletal pain, back pain, tachycardia. Cytokine release syndrome does not occur.

Patient Monitoring
Anaphylactoid reactions may occur, but have not been reported; frequent monitoring of routine vitals should be carried out after drug infusion.

Drug-Drug Interactions
None reported.

Dosage Forms
Intravenous only, 25mg/5mL vial (delivered to the floor as an IVPB).

Dosage and Administration
Recommended dose is 1mg/kg IV with first dose given the day prior to transplant and repeat doses at 14 day intervals for a total of five doses; the calculated dose is mixed with 50 mL of 0.9% sodium chloride solution and administered via a peripheral or central vein during a 15-minute period.

Compatibilities/Special Administration Techniques
DO NOT SHAKE; inspect visually for particulate matter and discoloration before administration – if present, do not use; assure sterility of the prepared solution, since the drug product does not contain any antimicrobial preservative or bacteriostatic agents; prepared infusion must be used within 4 hours, otherwise it may be refrigerated for up to 24 hours.

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