1. Transplant Medications Ed Horn, Pharm.D., BCPS Clinical Pharmacy Specialist – Transplant Allegheny General Hospital

3. Objectives By the end of this talk you should be able to: – Know the different types of medications used in transplant patients Anti-rejection Anti-infection – Know the side effects of transplant medications – Understand the follow-up required when taking anti- rejection medications

4. What Types of Medications Are Used After Transplant? Anti-rejection – Prevent your body’s immune system from attacking (rejecting) your new organ Tacrolimus (Progaf) Cyclosporine (Neoral, Gengraf, Sandimmune) Mycophenolate (CellCept, Myfortic) Prednisone Sirolimus (Rapamune, Rapamycin) Anti-infection – Prevent you from infection due to your body’s decreased ability to fight infection

5. What Types of Medications Are Used After Transplant? Anti-infection – Prevent you from infection due to your body’s decreased ability to fight infection Pneumonia –Bactrim –Dapsone Fungal infections –Clotrimazole (Mycelex Troches) –Fluconazole (Diflucan) –Voriconazole (Vfend) Viral infections –Acyclovir –Valganciclovir –Ganciclovir

6. Balance is key... Rejection Infection Side Effects Too Much Medication Not Enough Medication

7. Immunosuppressive Strategies Usually consists of 2-pronged approach: – Induction Potent immunosuppressant given in the ICU immediately after surgery Helps body accept newly transplanted organ easier – Maintenance – MOST IMPORTANT MEDICATONS Usually a 1-3 drug combination to start –Calcineurin inhibitor: PROGRAF or Cyclosporine –Anti-metabolite: CELLCEPT –Steroids: PREDNISONE

8. Anti-Rejection Medications Maintenance

9. Immunosuppressive Strategies Maintenance - PROGRAF Tacrolimus (PROGRAF) – Works by preventing the immune system from activating (“turning on”) – Usually taken two times per day 12 hours apart Ex: 8:00 a.m. and 8:00 p.m. If taken once daily, take at 8:00 a.m. – Blood levels are drawn to determine how much Prograf is in the body Usually need levels between 10-15 When having blood drawn, take Prograf AFTER – Can be taken with or without food – just keep it consistent!

10. Immunosuppressive Strategies Maintenance - PROGRAF Tacrolimus (PROGRAF) – Side Effects: Diabetes (high blood sugar) Hypertension (high blood pressure) Hyperlipidemia (high cholesterol and triglycerides, especially LDL - bad cholesterol) Renal insufficiency (decreased kidney function) Tremors (shaking hands) – Infection – Malignancy (certain types of cancer or lymphoma) Prograf has MANY drug interactions – do not take new medications (prescription or over the counter) before contacting your coordinator

11. Immunosuppressive Strategies Maintenance - CYCLOSPORINE Cyclosporine – Works by preventing the immune system from activating (“turning on”) – Usually taken two times per day 12 hours apart Ex: 8:00 a.m. and 8:00 p.m. If taken once daily, take at 8:00 a.m. – Blood levels are drawn to determine how much Cyclosporine is in the body Usually need levels between 200-300 When having blood drawn, take Cyclosporine AFTER – Can be taken with or without food – just keep it consistent!

12. Immunosuppressive Strategies Maintenance – CYCLOSPORINE Cyclosporine – Side Effects: Diabetes (high blood sugar) Hypertension (high blood pressure) Hyperlipidemia (high cholesterol and triglycerides, especially LDL - bad cholesterol) Renal insufficiency (decreased kidney function) Unwanted hair growth Gum overgrowth – Infection – Malignancy (certain types of cancer or lymphoma) Cyclosporine has MANY drug interactions – do not take new medications (prescirption or over the counter) before contacting your coordinator Cyclosporine has at least 3 brand/generic products! Make sure you are always taking the same one – Neoral – Sandimmune – GenGraf

13. Immunosuppressive Strategies Maintenance - CELLCEPT Mycophenolate (CellCept) – Works by decreasing the number of certain types of white blood cells that cause rejection – Usually taken two times per day with doses ranging from 1000mg-1500mg 2x/day Dose may be lower if white blood cell count is low or if infection is present – Can take with Prograf or cyclosporine – Do not crush tablets or open capsules

14. Immunosuppressive Strategies Maintenance - CELLCEPT Mycophenolate – CELLCEPT – Side effects: Decrease white blood count –found in blood tests Infection Nausea, vomiting, diarrhea Malignancy (certain types of cancer or lymphoma)

15. Immunosuppressive Strategies Maintenance - PREDNISONE Prednisone – Works by many different ways in the immune system to prevent rejection – One of the first medications used to prevent rejection in transplant patients – Can be continued long-term or tapered off after transplant Has many long term side effects – Should not be stopped abruptly Adrenal crisis – severe drop in blood pressure, loss of consciousness

16. Immunosuppressive Strategies Maintenance - PREDNISONE Side effects – Short term High blood pressure Elevated cholesterol - triglycerides, LDL-bad cholesterol Salt and fluid retention Diabetes (steroid induced) Poor wound healing Mood swings (extreme elation or depression) – Long Term Osteoporosis - weak bones Stomach ulcers Myopathy (muscle weakness) Cosmetic effects (full moon face) Thrush/fungal infections

17. Immunosuppressive Strategies Maintenance - RAPAMUNE Sirolimus (RAPAMUNE, rapamycin) – Works by preventing certain immune cells from multiplying – Used in combination with PROGRAF, Cyclosporine or with CellCept Usually taken once daily – Can be taken at the same time as PROGRAF – Must be taken 4 hours apart from cyclosporine Levels are monitored similar to PROGRAF

18. Immunosuppressive Strategies Maintenance - RAPAMUNE Side effects – Increases cholesterol, triglycerides and LDL levels – Decreases white blood cell counts and hemoglobin – Poor wound healing – Mouth ulcers – Infection – Malignancy (certain types of cancer-lymphoma) Drug interactions – Similar to PROGRAF and cyclosporine – Do not take any new medications before calling your coordinator

19. Infection Prevention Aside from rejection, biggest risk to transplant patients is infection – Bacterial – pneumonia, blood stream infections – Viral – gastritis, pneumonia, meningitis – Fungal Risk of infection is highest in first 6-12 months after transplant Type of infection depends on the organ transplanted

20. Rules To Live By... Do not take any new medications, even ones prescribed by your PCP, before calling your transplant coordinator Beware of herbal medications – Many have effects on the immune system Activation Suppression – May have interactions with anti-rejection medications

21. Summary Immunosuppressive agents are used to prevent rejection Balance between rejection, infection, and side effects must be maintained Medication regimens are complex with multiple drug interactions and side effects Proper monitoring of blood levels is mandatory to adjust medications