Transplant

Inhibits T-lymphocyte and B-lymphocyte proliferation by altering nucleotide (purine) synthesis

Mycophenolate MOA

Thiopurine methyltransferase activity; low or absent activity of the anzyme can lead to severe, life-threatening myelosuppression

What test should patients undergo when prescribed axathioprine?

A monoclonal antibody that binds to the CD52 receptor on T-lymphocytes, leading to T-lymphocyte depletion

Alemtuzumab MOA

Polyclonal antibodies that bind to antigens on T-lymphocytes, leading to T-lymphocyte depletion

Antithymocyte globulin MOA

A monoclonal antibody that binds to the IL-2 receptor on the surface of activated T-lymphocytes, inhibiting proliferation

Basiliximab MOA

Age-appropriate cancer screening as part of transplant candidate work-up

Recommendations for reducing skin cancer in transplant recipients pre-treatment

Seek shade during peak sunlight hours, wear long-sleeve shirt, use broad-spectrum sunscreen SPF ≥30 (apply 15-30 min before sun exposure & reapply every 2 hours), wear a hat with ≥2” brim, wear sunglasses to protect skin around the eyes, have professional assess skin annually

Recommendations for reducing skin cancer in transplant recipients post-transplant

Allopurinol inhibits the metabolism of azathioprine, leading to potentially fatal myelosuppresion and severe GI adverse effects

How does allopurinol impact azathioprine?

Post-transplant lymphoproliferative disorder, infections, liver transplant

Belatacept boxed warnings

Epstein-Barr virus and tuberculosis

What test should be taken and reviewed before administering belatacept to avoid serious adverse events?

Atgam: aplastic anemia, graft-versus-host disease, transplant induction, organ rejection; Thymoglobulin: transplant induction, organ rejection

Antithymocyte globulin uses

Infusion-related reactions/cytokine release syndrome (fever, chills, pruritis, hypotension), infections, leukopenia, thrombocytopenia

Antithymocyte adverse effects

CBC with differential, signs and symptoms of infection, vital signs during administration

Antithymocyte globulin monitoring

To avoid infusion-related reactions (cytokine re;ease syndrome)

Why are premedication and appropriate infusion rates required when administering antithymocyte globulin?

Tacrolimus and cyclosporine

Which transplant drugs are associated with nephrotoxicity?

Modified: Grengraf Neoral; Nonmodified: Sandimmune

Oral capsule & solution branded cyclosporine formulations

Sandimmune

Intravenous solution branded cyclosporine formulation

Restasis

Opthalmic emulsion branded cyclosporine formulation

Calcineurin inhibitor (Tacrolimus) + Antiproliferative agents (Mycophenolate) ± Steroid (Prednisone)

First-line maintenance immunosuppression

Carbamazepine, phenobarbital, phenytoin; CYP3A4 or p-glycoprotein inducers can lead to graft rejection if cyclosporine levels are not monitored carefully

Which antiepileptic drugs can increase the risk of graft rejection?

Difference in absorption

What is the main reason CellCept and Myfortic are not interchangeable?

At steady state right before, or typically 30 minutes before, the next dose is due

When are trough levels drawn?

They weaken the immune system so that it will not attack the transplanted organ

What is the purpose of using cyclosporine and mycophenolate post transplant?

Tacrolimus and cyclosporine; Inhibitors, including grapefruit, will increase the drug concentration and increase toxicity; Inducers will decrease the drug concentration and could result in graft rejection

Which transplant drugs are CYP450 3A4 and P-gp substrates?

Risk of embryo-fetal toxicity

Mycophenolate Risk Evaluation and Mitigation Strategy (REMS)

MMR II, Rotarix, RotaTeq, Varivax, Vaxchora, Vivotif, FluMist, YF-VAX

Common live vaccines

Decreased metabolism to active form; Decreased serum concentration & clinical efficacy

What effect do inhibitors have on substrate prodrugs?

Amiodarone, azole antifungals, cobicistat, cyclosporine, grapefruit, macrolides, non-DHP CCBs, protease inhibitors

Common CYP450 inhibitors

Immunosuppressants can increase the risk of infections & cancer, stay consistent in how you take your medications, many immunosuppressats require monitoring of drug levels, multiple strengths of the same medications may be prescribed to you, immunosuppressants have many drug interactions, avoid live virus vaccines & inform your transplant provider before getting vaccinated

Key counseling points for immunosuppressants & transplant recipients

Azathioprine, Everolimus, Steroids, Tacrolimus, Cyclosporine

Drugs used for chronic maintenance in transplant recipients

Antithymocyte globulin

Which drug is used for induction (to prevent acute rejection), not maintenance?

Calcineurin inhibitors

Cyclosporine and tacrolimus drug class

Use the syringe provided by the manufacturer to measure the dose; NO NOT rinse the syringe before or after use; Use a compatible diluent (orange juice) at room temperature; Mix the dose and diluent thoroughly in a glas container. DO NOT administer from a plastic or styrofoam cup; Administer or drink immediately. Rinse the container with extra diluent to ensure the total dose is taken

Administration of cyclosporine oral solution

Electrolyte disturbances, hyperglycemia, hyperlipidemia, hypertension, infections, nephrotoxicity, neurotoxicity, QT prolongation

Adverse effects of cyclosporine & tacrolimus

Gingival hyperplasia, hirsutism (hair growth)

Cyclosporine-specific adverse effects

Alopecia (hair loss)

Tacrolimus-specific adverse effects

AB

AB blood can give blood to (Universal receiver)

AB, A, B, O

AB blood can receive blood from

A, AB

A blood can give blood to

A, O

A blood can receive blood from

B, AB

B blood can give blood to

B, O

B blood can receive blood from

AB, A, B, O

O blood can give blood to

O

O blood can receive blood from (Universal donor)

Optimize maintenance immunosuppression; High-dose corticosteroids followed by an oral steroid taper; Antithymocyte globulin for aggressive acute cellular rejection or steroid-resistant rejection

Treatment of acute cellular rejection