PCT V complications after solid organ transplant exam 3

- calcineurin inhibitors
- antimetabolites
- mammalian target of rapamycin inhibitors (mTOR)
- corticosteroids
- fusion protein

maintenance therapy agetns

- tacrolimus
- cyclosporin

examples of calcineurin inhibitors

- azathioprine
- mycophenolate

examples of antimetabolites

- sirolimus
- everolimus

examples of mammalian target of rapamycin inhibitors (mTOR)

- methylprednisolone
- prednisone

examples of corticosteroids

- belatacept (IV)

examples of fusion protein

- CSA
- CYA
- sandimmune
- neoral
- gengraf

brand names for cyclosporine

- FK
- FK506
- progra
- envarsus
- astagraf XL

brand names for tacrolimus

true

T/F patients will be one either tacrolimus or cyclosporine, but not both

false, will be on one or the other but not both

T/F patients can be on both tacrolimus and cyclosporine

tacrolimus

which calcineurin inhibitor is more commonly used

sandimmune

non-modified, original formulation of cyclosporine

- neoral
- gengraf

modified, modern formulation of cyclosporine

neoral and gengraf (sandimmune is NOT interchangeable because it is the non-modified version)

which cyclosporine formulations are interchangeable

BID

cyclosporine frequency

false

T/F cyclosporine oral to IV conversion is 1:1

true

T/F cyclosporine oral to IV conversion is not 1:1

- astagraf XL
- envarsus XR

extended release tacrolimus formulations

QAM

frequency for astagraf XL

QAM

frequency for envarsus XR

- generic tacrolimus/brand name prograf

immediate release tacrolimus

BID

frequency for generic tacrolimus/brand name prograf

false

T/F astagraf XL and envarsus XR are interchangeable

true

T/F astagraf XL and envarsus XR are not interchangeable

start astagraf XL at a once daily dose that's the same as the total daily dose of IR tacrolimus (1:1)

conversion of IR tacrolimus to astagraf XL

start envarsus XR at a once daily dose that is 70-80% ot total daily dose of IR tacrolimus

conversion of IR tacrolimus to envarsus XR

tacrolimus

tacrolimus/cyclosporine is more potent

BID
- in rare occasions the immediate release for is given once daily

frequency for tacrolimus

false

T/F tacrolimus oral formulation to IV conversion is 1:1

true

T/F tacrolimus oral formulation to IV conversion is not 1:1

- azole antifungals
- erythromycin, clarithromycin, azithromycin
- lopinavir/ritonavir
- verapamil, diltiazem

drugs that increase tacrolimus/cyclosporine levels (CYP3A4 inhibitors)

- nafcillin
- rifampin
- efavirenz
- carbamazepine, phenytoin, phenobarbital

drugs that decrease tacrolimus/cyclosporine levels (CYP3A4 inducers)

- statins and red yeast rice: increases statin levels which increases adverse effects --\> myopathy
- herbal supplements

other drug interactions with tacrolimus/cyclosporine

either lower the dose of the statin or switch to pravastatin (because pravastatin does not interact)

management of statins/red yeast rice and tacrolimus/cyclosporine

grape fruit juice: increases tacrolimus/cyclosporine levels

food interactions with tacrolimus/cyclosporine

false, changes frequently
should emphasize to the patient to follow directions given to them by the provider and not what is on their prescription bottle (because those instructions are old)

T/F doses of tacrolimus and cyclosporine stays the same

true
should emphasize to the patient to follow directions given to them by the provider and not what is on their prescription bottle (because those instructions are old)

T/F doses of tacrolimus and cyclosporine change frequently

before

levels should be drawn before/after a dose of tacrolimus or cyclosporine is taken

patient should be 100% adherent

adherence with tacrolimus and cyclosporine

- decreased rates of early acute rejection, biopsy proven rejection and recurrent rejection
- less graft loss and death with tacrolimus

benefits of tacrolimus

- fewer neurologic side effects
- hair growth

benefits of cyclosporine

tacrolimus

tacrolimus/cyclosporine is the preferred calcineurin inhibitor

- hair loss
- post-transplant diabetes (more than cyclosporine)
- hyperlipidemia
- hypertension
- hypomagnesemia (more than cyclosporine)
- hypophosphatemia (more than cyclosporine)
- hyperkalemia (more than cyclosporine)
- nephrotoxicity (same as cyclosporine)
- neurotoxicity/tremor/CNS effects (more than cyclosporine)

adverse effects of tacrolimus

- hair growth
- post-transplant diabetes
- hyperlipidemia (more than tacrolimus)
- hypertension (more than tacrolimus)
- hypomagesemia
- hypophosphoatemia
- hyperkalemia
- nephrotoxicity (same as tacrolimus)
- neurotoxicity/tremor/CNS effects

adverse effects of cyclosporine

- mycophenolate mofetil
- mycophenoalte sodium/mycophenolic acid

types of mycophenolate

- MMF
- cellcept

brand name for mycophenolate mofetil

- MPA
- Myfortic

brand name for mycophenolate sodium/mycophenolic acid

true

T/F patients should be on azathioprine or mycophenolate, but not both

false

T/F patients should be on both azathiprine and mycophenolate

mycophenolate

which antimetabolite is more common? mycophenolate or azathiprine

1:1

mycophenolate IV to po conversion

- leukopenia
- thrombocytopenia
- anemia
- skin cancer
- pancreatitis
- lymphoma (rare)

adverse reactions of azathiprine

- xanthine oxidase inhibitors (allopurinol): increases levels, must reduce dose, myelosuppressive effects
- sulfasalazine

drug interactions with azathioprine

inhibits the de novo pathway of purine biosynthesis

mycophenolic acid mechanism

500mg MMF \= 360mg MPA

conversion of MMR to MPA

1000mg BID
(ranges from 250mg to 1500mg)

dose of MMF

false, check levels is controversial

T/F you should check blood levels with mycophenoalte

true

T/F you do not have to check blood levels with mycophenolate

- pantoprazole: not clinically significant
- cyclosporine: requires higher dose of MMF if used together

drug interactions with mycophenolate

- nausea, diarrhea--can lead to colitis
- leukopenia
- thrombocytopenia
- pregnancy category D

adverse effects of mycophenolate

- take with food
- do not cut or crush

how to manage nausea/diarrhea with mycophenolate

- pregnancy category D
- BBB for increased risk of congenital malformations and first trimester pregnancy loss--REMS program
- females should be counseled to use contraception and discontinue therapy 6 weeks prior to trying to conceive
- unknown if excreted into breast milk but recommended to avoid

pregnancy with mycophenolate

- decreased rates of early acute rejection
- decreased rates of treatment failures
- less bone marrow suppression

benefits of mycophenolate

- less GI distress compared to mycophenolate

benefits of azathioprine

none

drug interactions with corticosteroids

- elevated WBC with higher doses
- weight gain: fluid retention and increased appetite
- mood changes
- insomnia
- cushing's syndrome

adverse effects of corticosteroids

prednisone

most common corticosteroid

- 5-60mg QAM
- many patient will be on a taper following their transplant
- maintenance doses are usually < 10mg daily

dose of corticosteroid

true

T/F patients should be on either sirolimus or everolimus but not both

false

T/F patients should be on both sirolimus and everolimus

mTOR

which medication can be used in place of calcineurin inhibitors or anti-metabolites

QD

frequency of sirolimus

rapamune

brand name of sirolimus

zortress

brand name of everolimus

BID

frequency of everolimus

false

T/F everolimus is equivalent to affinitor

true

T/F everolimus is not equivalent to affinitor

- azole antifungals
- erythromycin, clarithromycin, azithromycin
- verapamil, diltiazem
- cyclosporine

drugs that increase mTORi levels

- nafcillin
- rifampin
- efavirenz
- carbamazepine, phenytoin, phenobarbital

drugs that decrease mTORi levels

- slows wound healing
- increased protein in urine
- increased cholesterol and triglycerides
- myelosuppression
- pulmonary toxicity

adverse effects of mTORi

sirolimus

which has better efficacy: sirolimus or everolimus

sirolimus

sirolimus/everolimus has the longer half life

sirolimus, contraindicated after surgery due to delayed wound healing

sirolimus/everolimus has more problems with wound healing

everolimus

sirolimus/everolimus has shorter half life

everolimus

sirolimus/everolimus dose adjustments are made earlier

- decreased nephrotoxicity
- potential anti-viral and anti-tumor benefits

benefits of mTORis vs calcineurin inhibitors

- less hypercholesterolemia
- less wound healing complications

benefits of calcineurin inhibitors vs mTORis

thymoglobulin or basiliximab with high dose corticosteroids

induction regimen examples

tacrolimus and mycophenolate with or without prednisone

maintenance regimen examples

most regimens include two or more agents
- corticosteroids
- antithymocyte globulin (thymoglobulin)
- bortesomib (velcade)
- eculizumab (soliris)
- plasmapheresis/plasma exchange

rejection treatment options

- technical/surgical complications
- net state of immunosuppression (use of antilymphocyte preparations, cormorbidities)
- recipient exposure (donor organ, noscomial, community)

risk factors for infection after transplant

- cytomegalovirus
- primary infection typically occurs in childhood or adolescence (asymptomatic or nonspecific)

50-90% of adults are \__________ virus positive

- donor(+) and recipient(-) \= high risk
- donor (+) and recipient (+) \= moderate risk
- donor (-) and recipient (+) \= moderate risk
- donor (-) and recipient (-)

risk of cytomegalovirus infection with donor/recipient serostatus

- pre-emptive monitoring
- acyclovir
- ganciclovir
- valganciclovir
- CMv hyperimmuen globulin

cytomegalovirus (CMV) prevention

HSV, not CMV

acyclovir cover which viruses

400mg BID
dose adjustment for renal function

dose for acyclovir

valganciclovir

prodrug of ganciclovir

3 months

duration for CMV low risk prophylaxis

3-6 months

duration of CMV moderate risk prophylaxis

6 months

duration of CMV high risk prophylaxis