Transplant Flashcards
Presentation of Rejection : Kidney
Increased ___ , and incr ___
Sx’s? (7)
Biopsy?
Scr (~20% rise) , BUN
weight gain, fever, malaise, oliguria, graft tenderness, edema, HTN
diffuse infiltration of lymphocytes
Presentation of Rejection : Liver
Incr ??
Sx’s ??
What would liver biopsy show u?
AST, ALT, Tbili, alk phos
fever, lethargy, change in color/quantity of bile, graft tenderness, back pain , anorexia,
sometimes difficult to distinguish from recurrent disease like Hep C or Hep B
Presentation of Rejection : Heart
High incidence of ?
Often difficult to ??
Sx’s?
Acute rejection
diagnose clinically
low grade fever, lethargy, weakness, SOB, DOE, hypotension , tachycardia, atrial flutter, ventricular arrhythmias, leukocytosis
TX of Acute Rejection
Depends on Severity : Describe what u would do in each scenario
- Changing maintenance regimen
- Steroid pulse therapy
- Steroid resistant therapy
- a. Increase tacrolimus
b) Add a secondary agent
c) Switch from cyclosporine to tacrolimus - Methylprednisolone 500 mg - 1 gram IV per day for 3-5 days followed by taper to pre-rejection steroid dose
- a) Thymoglobulin 1 - 1.5 mg/kg IV daily administered over 4-6 hours x 5 days
OR
b) Antithymocyte Globulin (Atgam® ) 10-15 mg/kg IV daily x 5 days. Need skin test prior to administration
Calcineurin Inhibs : Cyclosporine and Tacrolimus
-NEVER ____
CYCLOSPORINE :
-Primarily used as ?
Dosing?
AVailable as what formulations?
What do u use to guide dosing ?
Therapeutic range?
used together
Alternative to tacrolimus : for neurotoxicity or uncontrolled diabetes with tacrolimus,
Initial Oral Dose : 5-15 mg/kg/day (divided BID)
25 mg, 100 mg capsules, IV and liquid
Therapeutic drug monitoring
100-250 ng/mL
Tacrolimus
-Most widely used immunosuppressant
-Primary agent used together with?
-What can be substituted if AE’s too strong?
-Available as what formulations?
Dosing?
1 or 2 additional agents
Cyclosporine
0.5mg, 1mg, 5mg capsules; IV and suspensions
Initial oral : 0.15 - 0.3 mg/kg/day divided BID
Tacrolimus Drug level Monitoring
-Using ___
Therapeutic levels? (titrated to the individual!)
Target Trough level depends on ?
Trough concentrations
5-15 ng/mL
time post-transplant
- organ transplanted
- etiology of organ failure
- h/o rejection
- concomitant immunosuppression
- adverse effects
- other disease states
- age (baseline immunosuppressive state
Differences between cyclosporine and tacro
Tacro can do what?
It has a greater incidence of?
It has a LOWER incidence of?
there’s decr tremor with what formulation of tracro?
The initial Envarsus dose is ?
tacro currently only approved for?
TREAT REJECTION (in some cases)
HYPERglycemia, tremor
HTN,Gingival hyperpasia, hirsutism
LCPT (Envarsus)
-80% of total daily IR-Tac (Prograf)
Kidney transplant
Calcineurin inhib Interactions:
CYP3A inhibs (7)
CYP3A Inducers (5)
PGP (Only worried about this for cyclosporine)
Grapefruit juice, protease inhibs, azole antifungals , macrolide antibiotics (erythro, clarithro), Letermovir, Non DHP CCB’s , amiodarone
Rifampin, phenytoin, carbamazepine, phenobarb, sjw
INCR CONCS of sirolimus, everolimus, digoxin, statins
CNI Nephrotoxicity Tacro and Cyclo
Acute is reversible and ___
Chronic –> Whats affected , what can it cause , what can it do to ur electrolytes?
dose dependent
vessels, tubules, glomeruli
chronic interstitial fibrosis
hyperkalemia, hypomagnesemia, hyperuricemia
CNI WIthdrawal in Kidney Transplant :
-180 days post transplant what regimen do u change ur pt’s to
Dosing for MMF and sirolimus
This improved ?
Change ur pt’s from CNI/MMF to Sirolimus/MMF 30-180 days post transplant
MMF : 2 grams per day, Siro trough levels of 8 ng/mL
Renal function
Mycophenolate Mofetil (Cellcept)
-Most commonly used ___
Dosing ?
Available as ?
Drug Interactions (3)
Dose limiting AE’s?
BBW in Pregnancy ?
What’s suggested if a woman of childbearing potential?
secondary agent
1 gm po BID
1.5 gm BID if AA
250,500 mg caps, IV, suspension
Antacids, cholestyramine, (Decreased absorption), and PPI’s cause decr mycophenolic acid
GI (N/V/D) , BM suppression
Incr risk of 1st trimester preg loss and congenital malformations, REMS program
Contraception during tx and 6 weeks after they stop mycophenolate
Mycophenolic Acid (Myfortic)
-Active form
ALternative to ___ if ___
Dosing?
Dose conversion between cellcept and myfortic?
Available as ___ and ___ tablets
mycophen mofetil, GI AE’s such as d,n,v, intolerable
720 mg po BID
cellcept 250 mg = myfortic 180 mg
360 mg and 180 mg tabs
Azathioprine
-Alternative to ___
-CPIC guidelines recommend what
AE’s ?
DDI?
mycophenolate
TPMT genetic testing. Low/deficient -> Consider alt agent or extreme dose reduction
Intermediate : Start at 30-70% of target dose
Bone marrow suppression, myopathy,
alopecia, pancreatitis, hepatitis
allopurinol – inhibits xanthine oxidase which increases risk for azathioprine toxicity
MTOR Inhibitors : Sirolimus, Everolimus
What is it’s place in therapy? –>
Can be used as alt to ?
___ sparing - use with low dose ___
ANTI __,___,___
Concentration Guided dosing :
half life?
target levels ?
Sirolimus avail as ?
AE’s?
Mycophenolate mofetil
renal, tacrolimus
cancer, atherogenic, fibrotic
Long t1/2: 60 hours (sirolimus); 16-35 hours (everolimus)
(3-10 ng/mL)
0.5 mg, 1 mg, 2 mg tablets, liquid
Impaired wound healing
* Start later post-operatively; need to d/c and re-start if major surgery
* Bone marrow, dyslipidemias, proteinuria, mouth ulcers, angioedema (rare)
* (Black Box warning for use in liver and lung transplantation)
