Immunosuppressants

  1. The conversion ratio of PO:IV for cyclosporine
    3:1 PO:IV
  2. Are generic cyclosporine formulations such as Gengraf interchangeable with Neoral?
    Yes
  3. What is the standard of care at most insitutions for monitoring CSA?
    Pre-dose trough whole blood concentration
  4. Single point sampling 2 hours after CSA administration
    • Provide a simplified and acurate marker of immunosuppressive efficacy and toxicity
    • Correlates better with AUC
  5. What is the initial dose of CSA?
    2.5 mg/kg PO q 12
  6. What it the target therapeutic range of CSA during the first 6 months post-txp kidney and liver?
    200-300 ng/mL
  7. What is the target therapeutic range for CSA during the first 6 months post-txp heart/lung?
    300-400 ng/mL
  8. How often do you monitor the steady state levels of CSA?
    • 3 times/week x 1 month
    • 2 times/week x 2 months
    • 1 time/week x 3 months
    • Monthly thereafter or after any dose changes
  9. By what amount should CSA doses be adjusted?
    25-50 mg PO a 12 hour to achieve therapeutic levels
  10. Does Neoral have a large or small Vd?
    Large 3-7 L/kg
  11. Does Neoral have a high or low F?
    Low-- 30%
  12. Is Neoral heavily renally eliminated?
    No
  13. What is the half life of Neoral?
    12-16 hours
  14. What is the PO:IV ratio for tacrolimus?
    3:1
  15. Does oral tacrolimus have good or poor absorption?
    Poor
  16. What is the standard of care for monitoring TAC?
    Pre-dose trough whole blood concentration
  17. What is the Tacrolimus dose?
    0.075 mg/kg PO Q 12 hours
  18. What is the therapeutic range for tacrolimus?
    5-15 ng/mL
  19. When should you monitor steady state of tacrolimus?
    • 3 times/week x 1 month
    • 2 times/week x 2 months
    • 1 time/week x 3 months
    • Monthly thereafter or after any dose changes
  20. By what amount should tacrolimus doses be changed?
    1-2 mg PO q 12
  21. Which drug should be separated from cyclosporine by at least 4 hours?
    Sirolimus
  22. What is the 1/2 life of siroliumus?
    57-63 hours
  23. Sirolimus dose for low-moderate immunologic risk patients (kidney, liver)
    6 mg LD followed by 2 mg QD
  24. Siroliumus dose for high immunologic risk patients (intestines, heart, lungs)
    15 mg LD followed by 5 mg QD
  25. What is the therapeutic range of sirolimus?
    5-15 ng/mL
  26. When should steady state concentrations of sirolimus be obtained?
    • Weekly x 1 month
    • Monthly- every 3 months thereafter or after any dose change
  27. By what increment should the sirolimus maintenance dose be adjusted?
    1-2 mg/day
  28. What is the most abundant and active CYP 450 enzyme in the liver and small intestine?
    3A4
  29. Where are P-glycoprotein's found?
    apical side of the brush border in enterocytes
  30. Do P-glycoproteins pump lipophilic or lipophobic substrates into the intestinal lumen?
    Lipophilic
  31. List the drugs/drug classes that are 3A4/P-gp inhibitors
    • Macrolides (except azithromycin)
    • Non-DHP CCB
    • Azole antifungals ( ketoconazole, voriconazole, itraconzole are the worst)
    • Protease inhibitors
  32. List the drugs/drug classes that are 3A4/P-gp inducers
    • Phenobarbital
    • Phenytoin
    • Rifampin/Rifabutin
    • Carbamazepine
  33. What is the maximum dose of a statin in a transplant patient?
    1/2 the max dose for a healthy patient
  34. Are CSA, TAC/SRL inhibitors or inducers of 3A4? Are they substrates?
    Inhibitors and substrates
  35. What are 3 complications of myoglobin release?
    • Renal vasoconstriction
    • Tubular toxicity
    • Intraluminal cast formation
  36. Is grapefruit juice an inhibitor or inducer?
    Inhibitor of CYP 3A4 in the gut
  37. Describe the effects of grapefruit jucie on the Cmax, AUC, Cl, and t1/2 for CSA/TAC/SRL
    • Increase Cmax and AUC
    • No change on Cl and t 1/2
  38. What part of grapefruit is responsible for the inhibition?
    • Naringin
    • Naringenin-metabolite
    • 6'7' dihydroxybergamottin
  39. Is St John's wort an inducer or inhibitor?
    Inducer
  40. Does St. John's Wort increase or decrease the bioavailability of CSA/TAC/SRL?
    Decrease
  41. What are some risks of supratherapeutic levels of SRL?
    • Anemia
    • Leukopenia
    • Thrombocytopenia
  42. Which drug is related to tremors if level is supratherapeutic?
    Tacrolimus
  43. When should you monitor CSA/TAC levels after starting an enzyme inhibitor?
    Monitor trough level 2-3 days after drug initiation and monitor dosage appropriately
  44. When should you monitor SRL levels after starting an enzyme inhibitor?
    1 week after drug initiation
  45. Which drugs should prophylactically be adjusted when combined with an enzyme inducer?
    • CSA/TAC
    • Increase by 25%
    • Monitor 4-7 days after drug initiation
Author
rclee06
ID
144626
Card Set
Immunosuppressants
Description
PK
Updated