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Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause HYPERlipidemia?
Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause Myocardial Hypertrophy?
- Same risk
- May be due to HTN
Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause Hirsutism?
Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause Alopecia?
Is Tacrolimus (FK506) or Cyclosporine (CsA) more likely to cause electrolyte imbalances?
What types of electrolyte imbalances are common with Calcineurin inhibitors?
Increased K and decreased Mg
What drugs cause increased Calcineurin inhibitor levels?
- Macrolides (Azith, Clarith, Eryth, Telith)
- Grapefruit juice
What drugs cause decreased Calcineurin Inhibitor levels?
- Phenytoin, Phenobarbital, Carbamazepine
- St. John’s Wart
What is the MOA of Sirolimus (Rapamune)?
- Macrolide immunosuppressant
- Binds to FK, which binds to mTOR
- Inhibits T cell proliferation by inhibiting cellular response to IL-2
- Prevents B cell differentiation/antibody production
- Also has antifungal and antitumor properties
When is Sirolimus (Rapamune) used/not used?
- Renal transplants (low-high risk)
- Higher risk of hepatic artery thrombosis = so not best for liver transplant
What are the dosing/admin considerations for Sirolimus (Rapamune)?
- No body weight dosing
- Load: 6 mg PO ASAP postop
- Maintenance: 2 mg PO QD
- 1 & 2 mg tablets
- Avoid light
What monitoring should be done for Sirolimus (Rapamune)?
- 1st year Trough: 16-24 ng/mL
- > 1 year postop Trough: 12-20 ng/mL
- Concurrently w/ CsA: 10-15 ng/mL
What are the AE for Sirolimus (Rapamune)?
- CYP3A4 and pgp substrate and inhibitor
- Vori and Keto CI (increases conc 10x)
When is Everolimus (Zortress) used/not used?
- Only for Kidney Transplant LOW-MOD
- Not used in severe risk patients
What are the dosing/admin concerns for Everolimus (Zortress)?
- No loading dose
- Take w/ or w/o food, but be consistent
What is the MOA for corticosteroids?
- Inhibition of Cytokines (IL-1,2,3,6 & TNFa)
- Interfere w/ cell migration and recognition
- Inhibition IL-1 secretion from macrophages
- Decreased IL-2 secretion from T cells
- Inhibit generation of CD8+ T cells
What is a normal dose of Corticosteroids during induction?
IV methylpred 3 mg/kg
What is a normal dose of Corticosteroids during maintenance therapy?
- IV Methylpred Postop day 1: 0.5-2 mg/kg
- Transition to PO
- Taper over next months to 5-20 mg QD
What drugs are considered Calcineurin Inhibitor sparing?
What are the AE of Corticosteroids?
- Increased appetite/weight
- Glucose intolerance
What is the MOA of Mycophenolate (MMF)?
- Selective, reversible inhibitor or inosine monophosphate dehydrogenase (IMPDH) needed for purine synthesis
- Specific for T cells and B cells (more so than Azathioprine)
When is Mycophenolate (MMF) used/not used?
- Common for both liver and kidney disease
- In combo with a Calcineurin inhibitor
What are the pharmacokinetics of Mycophenolate (MMF)?
- Absorption of 75% or more
- Increased AUC may occur after chronic use due to enterohepatic recirculation – dose adjust as needed
- Hepatic metabolism
- Renal tubular secretion
What DDIs does Mycophenolate have?
- Increases Acyclovir and probenecid – competes for renal tubular secretion
- Bile acid resins (cholestyramine, etc.) and Al or Mg based antacids – decrease MMF by 40%
What Antacids are AL or Mg containing?
- Mg: Equate, Maalox lq, Milk of Magnesia, Rennie, Mylanta, Rolaids and Gelusil
- Al: Equate, Malox lq and Tabs, Mylanta and Gelusil
What are the dosing/admin concerns for Mycophenolate (MMF)?
- 100 mg Cellcept: 720 mg Myfortic
- Cellcept: 1-1.5g BID, 250 caps and 500 mg tabs
- Myfortic: 720 BID PO, 180 mg and 360mg tabs – better if GI issues occur with Cellcept