CHAPTER 44: Pharmacology

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- = postoperative 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 3–7 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 patients receive 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 PO suspension

  • Two formulations ...