Ch. 56 Transplant

Stabinsky

prevention of graft rejection

an allograft is from one individual to another

transplant from a genetically identical donor (identical twins) is an isograft

an autograft is a transplant in the same patient

rejection occurs when the body has an immune response to the allograft

HLA and ABO blood group is used to find a match

AB

can give blood to AB

can receive blood from AB, A, B, O

** universal receiver

A

can give blood to A, AB

can receive blood from A, O

B

can give blood to B, AB

can receive blood from B, O

O

can give blood to AB, A, B, O

can receive blood from O

** universal donor

boxed warnings for transplant drugs overlap

infection risk

cancer risk

only experienced prescribers can prescribe transplant drugs

induction immunosuppression

induction immunosuppression is used to prevent acute rejection during the early post-transplant period, most often combined with high dose IV steroids

commonly used induction drug, basiliximab, an IL-2 antagonist, is only for prevention

antithymocyte globulin is for both induction and treatment

basiliximab

IL-2 antagonist --> chimeric monoclonal antibody that inhibits the IL-2 receptor on the surface of T-lymphocytes

simulect

antithymocyte globulin

binds to antigens on T-lymphocytes and interfere with their function

atgam - equine, thymoglobulin - rabbit

BBW --> anaphylaxis

SEs --> ISR

notes --> premedicate (diphenhydramine, APAP, steroids) to lessen the ISR

maintenance immunosuppression

uses multiple mechanisms with different drug classes to lower toxicity risk and reduce the risk of graft rejection

combo of -->

calcineurin inhibitor --> tacrolimus is first line

antiproliferative agent --> mycophenolate is first line

with or w/o steroids

calcineurin inhibitors

inhibit T-lymphocyte activation

cyclosporine (gengraf, neoral - modified; sandimmune - nonmodified)

tacrolimus (prograf, envarsus XR)

cyclosporine BBW

increased risk of malignancy (lymphoma, skin cancer)

increased risk of infection

nephrotoxicity

increased BP

modified and nonmodified are not interchangeable

cyclosporine SEs

increased BG

HLD

hyperkalemia

hypomagnesemia

hirsutism

gingival hyperplasia

neurotoxicity

hyperuricemia

cyclosporine monitoring

trough levels

serum electrolytes (K, Mg)

renal function

LFTs

BP

BG

lipids

cyclosporine notes

numerous drug interactions --> CYP3A4 inhibitor and a 3A4, Pgp substrate

do not administer from a plastic or styrofoam cup

tacrolimus BBW

increased risk of malignancy

increased risk of infection

tacrolimus SEs

increased BP

increased BG

HLD

nephrotoxicity

hypomagnesemia

hyperkalemia

alopecia

neurotoxicity

tacrolimus monitoring

trough levels

serum electrolytes (K, phos, Mg)

renal function

LFTs

BP

BG

lipids

tacrolimus notes

do not interchange

CYP3A4 and Pgp substrate

food decreases absorption

IV must be in a non-PVC bag

antiproliferative agents

alter purine nucleotide synthesis

azathiopurine (azasan, imuran)

mycophenolate mofetil (cellcept)

azathiopurine

BBW --> increased risk of malignancy

warnings --> myelosuppression due to a genetic deficiency of TPMT

mycophenolate

BBW --> increased risk of malignancy, increased risk of infection, and increased risk of congenital malformations and spontaneous abortions

SEs --> N/V/D, abdominal pain, leukopenia

notes --> cellcept and myfortic are not interchangeable

myfortin is EC to decrease diarrhea

cellcept IV is stable in D5W only

decreases efficacy of oral contraceptives

mTOR kinase inhibitors

inhibit T-lymphocyte activation/proliferation

everolimus (zortress)

sirolimus (rapamune)

mTOR kinase inhibitor BBW

increased risk of malignancy

increased risk of infection

mTOR kinase inhibitor warnings

HLD

impaired wound healing

pneumonitis (DC if this develops)

do not use everolimus within 30 days of transplant

mTOR kinase inhibitor SEs

peripheral edema

increased BP

increased BG

mTOR kinase inhibitor monitoring

trough levels

mTOR kinase inhibitor notes

numerous drug interactions --> 3A4 and Pgp substrate

sirolimus tablet and oral solution are not bioequivalent

belatacept

nulojix

binds to CD80 and CD86, blocking costimulation with CD28 on T-lymphocytes

BBW --> increased risk of post-transplant lymphoproliferative disorder (PTLD); use with EBV seropositive patients only, increased risk of infection and malignancies

warnings --> treat latent TB prior to use

prednisone short-term SEs

fluid retention

stomach upset

emotional instability

insomnia

increased appetite

weight gain

acute risk in BG and BP

prednisone long-term SEs

adrenal suppression/cushing's

impaired wound healing

increased BP

diabetes

acne

osteoporosis

impaired growth in children

what's used and when?

induction -->

-basiliximab, an IL-2 antagonist

- antithymocyte globulin in patients at higher risk of rejection

- high-dose IV steroids

maintenance -->

- CNIs (belatacept is an alternative)

- antiproliferative agent

- mTOR inhibitor

- steroids at lower or tapering doses

drug interactions

cyclosporine inhibits 3A4 --> cyclosporine and tacrolimus are substrates of 3A4 and Pgp --> inducers of either will decrease drugs concentration and inhibitors will increase it (both interact with a majority of drugs)

mycophenolate can decrease levels of oral contraceptives

avoid using azathiopurine with XOIs

pharmacodynamic interactions

caution with additive drugs that -->

are nephrotoxic with CNIs

raise BG with steroids, CNIs

worsen lipids with mTOR inhibitors

raise BP

are myelosuppressive with azathiopurine and mycophenolate

drug food and natural product interactions

avoid grapefruit juice and st. john's wort

monitoring by patient and health care team

common symptoms of acute rejection include flu-like symptoms --> decrease in urine output, fluid retention

require careful monitoring (trough levels drawn 30 min before scheduled dose)

all patients should self monitor for symptoms of infection

acute rejection

arises from either T-cell (cellular) or B-cell (humoral or antibody)

can determine type through biopsy

initial approach is the admin of high-dose steroids

reducing infection risk

can be bacterial, viral, or opportunistic

infection prophylaxis is essential, especially in the first 6 months post transplant after receiving treatment for acute rejection

need routine infection control

live vaccines cannot be given post-transplant

vaccine-preventable illness in transplant recipients

required vaccines are given pre-transplant is needed

inactivated vaccines can be given 3-6 months post-transplant, except for the flu vaccine, which can be given 1 month post-transplant

live vaccines cannot be given post-transplant

important vaccines for transplant recipients

flu annually

pneumococcal

varicella --> pre-transplant and close contacts

hepatitis B (pre or post)

all immunosuppressant counseling

take exactly as prescribed; stay consistent

measure the lowest trough level 30 min before next dose

tacrolimus counseling

take every 12 hours, or once daily in the morning for XL or XR formulations

CONSISTENCY

avoid grapefuir

mycophenolate counseling

requires a medguide

can cause stomach upset

avoid in pregnancy; birth control pills do not work as well

drug interactions due to binding --> avoid taking antacids and vitamins at the same time

administration of cyclosporine

use the syringe provided by the manufacturer to measure the dose

do not rince the syringe before or after use

use a compatible diluent at room temp (orange juice)

mix the dose and diluent thoroughly in a glass container. do nto adminsiter in plastic or styrofoam

adminsiter or drink immediately. rinse the container with extra diluent to ensure the total dose is taken