Solid Organ Transplant - Treatment

induction treatment options

thymoglobulin
Alemtuzumab
basiliximab

when is thymoglobulin used

induction
rejection

polyclonal IgG againist human T-lymphocytes from horses

thymoglobulin

causes lymphocyte depletion

thymoglobulin
alemtuzumab

AE: leukopenia, thrombocytopenia, fever, chills

thymoglobulin

alemtuzumab use

off-label induction

humnaized anti-CD52 monoclonal antibody

alemtuzumab

antibody dependent cellular toxicity → profound depletion fo T cells

alemtuzumab

AE: infusion reactions, chills, rigor, fever

alemtuzumab

basiliximab use

induction
if h/o malignancy, high infection risk, immunocompromised, HIV, untreated HCV, age >65

recombinant chimeric monoclonal antibody agiainst CD25

basiliximab

non lymphodepleting

basiliximab

maintenance options

CNI
antimetabolites
mTOR inhibitors
corticosteroids
T-cell costimulation blocker

cyclosporine

CNI

tacrolimus

CNI

cyclosporine metabolism

CYP3A4
pgp

T or F non-modified and modified formulations of cyclosporine are interchangable

F

which tacrolimus formation is preferred and why

ER
less ADE and increased adherence

more potent CNI

tacrolimus

tacrolimus trough levels

5-15

CNI with highly variable elimination

cyclosporine (long t1/2)

tacrolimus metabolism

CYP3A4

AE: hypertension, hypercholesterolemia. hypertriglyeridemia, gingival hyperplasia, hirsutism

cyclosporine

AE: neurotoxicity (headache, insomnia, tremor, dizziness), hyperglycemia, PTDM, alopecia

tacrolimus

drugs that reduce CNI concentration

inducers
phenytoin
carbamazepine
phenobarbital
rifampin

drugs that increase CNI concentrations

inhibitors
erythromycin, clarithromycin
azoles
non DHP CCB
ritonavir
grapefruit juice

why type of organ dysfunction will increase tacrolimus t1/2

liver

purine analog that incorporates into nucleic acid and inhibits RNA and DNA synthesis to stop cell proliferation

Azathiopurine

AE: GI, BMS

Azathiopurine

Azathiopurine drug interactions

allopurinol, febuxostat

inhibit de novo synthesis pathway of purine synthesis → limits progression of activated B and T cells

mycophenolic acid

AE: teratogenic, REMs, 2 forms of birth control

mycophenolic acid

mycophenolic acid drug interactions

valganciclovir
sirolimus

avoid immediately post transplant due to imparied wound healing

mTOR inhibitors

binds to FKB12 whihc fuses with mTOR → inhibits T cell proliferation

mTOR inhibitors

used in combination with CNI or corticosteroids

mTOR inhibitors

mTOR inhibitors metabolism

CYP3A4
pgp

AE: edemia, HLD, HTD, imparied wound healing, mouth ulcers, proteinuria

mTOR inhibitors

sirolius

mTOR inhibitors

everolimus

mTOR inhibitors

sirolimus approved for

kidney transplant rejection prophylaxis

everolimus approved use for

kidney and liver transplant rejection prophylaxis

inhibit cytokine production by T cells and macrophages, blocks transcription

corticosteroids

belatacept

T-cell costimulation blocker

contraindicated in liver transplant

belatacept

blocks signal-2 of T cell activation

belatacept

IV only

belatacept

contraindicated in EBV seronegative patients

belatacept

triple drug regimen contains

Tacrolimus + mycophenolate ± prednisone

rejection therapy
acute cellular rejection
mild-moderate treatment

high dose methylprednisone

rejection therapy
acute cellular rejection
moderate-severe/steroid resistant

thymocyte or alemtuzumab (refractory)

rejection therapy
antibody mediated rejection treatment

steroids ± rituximab ± IVIG

rituximab use

antibody mediated rejection

anti-CD20 chimeric monoclonal antibody

rituximab

intravenous immune globuline (IVIG) indiation

desensitization protocols in SOT
treatment of antibody medicate rejection

PJP, PCP treatment

bactrim

CMV treatment

valganciclovir

candida, aspergillus (lung) treatment

posaconazole