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INDUCTION IMMUNOSUPPRESSION

  • The primary goal of immunosuppression is to prevent rejection of the new graft and minimize drug toxicities.

  • Induction therapy provides intense immunosuppression at the time of transplant when immune response is the greatest.

Basiliximab (Simulect)

  • Class: Monoclonal antibody (nonlymphocyte depleting)

  • Mechanism of action: Binds to interleukin 2 (IL-2) receptors on activated T cells, inhibiting activation and proliferation

  • Dosage forms: 10 mg and 20 mg vial for intravenous (IV) infusion

  • Dosing: Given on post-=operative day 0 and 4

    • 10 mg if patient <35 kg

    • 20 mg if patient >35 kg

  • Adverse drug effects: Well tolerated but can cause abdominal pain, vomiting, dizziness, insomnia, edema, and hypertension

  • Additional information: Basiliximab is the recommended agent for patients who are not considered high immunologic risk

Rabbit Antithymocyte Globulin (Thymoglobulin)

  • Class: Polyclonal antibody (lymphocyte depleting)

  • Mechanism of action: Binds to T-cell surface antigens and depletes CD4 lymphocytes from circulation and induces apoptosis of activated T cells

  • Dosage forms: 25 mg vial for IV infusion

  • Dosing: 1.5 mg/kg IV daily for 3 to 7 days

    • Usual maximum dose of 150 mg

  • Adverse drug effects: Leukopenia and thrombocytopenia (requires dose adjustment), cytokine release syndrome (requires premedication), serum sickness, edema, hyperkalemia, and acute renal failure

  • Additional information: Recommended for use in patients at high immunologic risk of rejection

Alemtuzumab (Campath)

  • Class: Monoclonal antibody (lymphocyte depleting)

  • Mechanism of action: Binds to CD52 antigen and causes depletion of T and B cells, monocytes, and natural killer (NK) cells through antibody-dependent, cellular-mediated lysis

  • Dosage forms: 30 mg/mL solution for IV infusion

  • Dosing: 30 mg IV once at time of transplant

  • Adverse drug effects: Thrombocytopenia, leukopenia, anemia, cytokine release syndrome (requires premedication), nausea, vomiting, insomnia, anxiety, and infusion-related reactions

Methylprednisolone (Solu-MEDROL) Prednisone (Deltasone)

  • Class: Corticosteroid

  • Mechanism of action: Nonspecific inhibitor of cytokines, antigens, and tumor necrosis factors to decrease the production of IL-2 and reduce B-cell proliferation

  • Dosage forms:

    • Prednisone: 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg tablets; 1 mg/mL oral solution

    • Methylprednisolone: 40 mg/mL, 125 mg/2mL, 500 mg vial, and 1 g vial

  • Dosing: Variable depending on indication

  • Adverse drug effects: Hypokalemia, hyperglycemia, osteoporosis, hypertension, insomnia, gastritis, ulcers, edema, euphoria, and depression

MAINTENANCE IMMUNOSUPPRESSION

  • After a patient receives a transplant they will need to suppress their immune system for the rest of their life; less intense medications compared to induction agents.

Cyclosporine (CSA) (Modified: Neoral, Gengraf) (Nonmodified: Sandimmune)

  • Class: Calcineurin inhibitor (CNI)

  • Mechanism of action: Prevents T-cell activation by forming a complex with calcineurin and cyclophilin to prevent transcription factors from entering the nucleus and upregulating the production of IL-2

  • Dosage forms: 25 mg, 50 mg, and 100 mg capsules; 100 mg/mL oral suspension

    • Two formulations are ...

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