RX PREP TRANSPLANT

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1

What 2 organs are the most common transplant sites?

  • Kidney and liver transplants
2

3 mechanism responsible for graft rejection?

  1. Human leukocyte antigen (HLA)
  2. ABO blood group
  3. Panel Reactive Antibody (PRA) test!

Before you even think about shoving another person’s organ into somebody else - check to make sure if their body will even accept it!

3

This test gauges the degree to how “sensitized” the recipient is to foreign/”non-self” proteins___?

Panel Reactive Antibody (PRA) test!

  • This test gauges the degree to how “sensitized” the recipient is to foreign/”non-self” proteins. Higher score = higher likelihood to REJECT.
  • This is literally one of the few times where you DON’T want a high score lmao.
4

___ is

  • transferring from one different person to another.
  • Allograft (aka homograft)
5

___is

  • transferring from a genetically identical person to another (i.e. identical twins)
  • Isograft
6

___ is

  • transferring from the same person to a different site on the same person.
  • Autograft (aka autologous)
7

Types of organ rejection that___:

  • occurs literally right then and there in the operating room within hours of the transplant due to HLA or ABO mismatch.

Hyperacute rejection

  • No treatment exists - the graft must be removed in order to avoid death!
8

Types of organ rejection that___:

  • occurs usually in the first 3 months, but really, it can occur anytime.
  • Acute rejection
9

Types of organ rejection that___:

  • long-term rejection that slowly leads to failure of the transplanted organ.
  • Chronic rejection
  • No treatment exists.
10

Induction immunosuppression should be done when___

  • given BEFORE or AT THE TIME of transplant in order to prevent acute rejection. How we do this is basically weaken the body so much it can’t even fight back, and it’s forced to accept the graft.
11

What drugs to use to

  • INDUCTION IMMUNOSUPPRESSION?

Usually consists of a short course of IV immunosuppressants +/- high-dose IV steroids.

  • Basiliximab (Simulect)
  • Antithymocyte globulins (Atgam - equine [horse]; Thymoglobulin - rabbit)
12

What's the brand & MoA for

  • Basiliximab
  • Simulect
  • MoA = IL-2 receptor antagonist
13

What is the ADRs for Basiliximab (Simulect)?

  • well-tolerated since it’s a chimeric human mAb
14

What is the monitoring for Basiliximab (Simulect)?

  • S/S hypersensitivity and infection
15

T/F.

Simulect can be used to prevent and treatment of rejection.

FALSE

  • Can only be used for the prevention of rejection ONLY!
16

Name 2 Antithymocyte globulins?

    1. Atgam - equine [horse]
  • Thymoglobulin - (rabbit
17

What are MoA for Antithymocyte globulins?

  • Reverses rejection via binding to antigens on T-lymphocytes (killer cells) and interfering with their function
18

What are AEs for Antithymocyte globulins?

  • infusion-related reactions
19

In which kind of transplant you DONT HAVE TO induce immunosuppression?

  • if it’s a transplant between identical twins!
20

What is the purpose of using multiple drugs in transplant?

  • we use multiple drugs in order to lower the risk of individual drug toxicity, while maintaining the same state of immunosuppression!
21

What's the typical regimen for transplant?

[1] calcineurin inhibitor + [2] anti-proliferative agent +/- [3] steroids

22

Name some

CALCINEURIN INHIBITORS (CNIs)?

  1. Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  2. Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
23

What are the brand for Tacrolimus?

  • Prograf, Astagraf XL, Envarsus XR
24

What is the brand for Topical eczema tacrolimus?

  • Protopic
25

What are some BBW for

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)?
  1. Increased susceptibility to infection
  2. Possible development of lymphoma
  3. Extended-release formulation (Astagraf XL) associated with increased mortality in female liver transplant recipients
26

What are some AEs of

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)?
  1. Hypertension
  2. Nephrotoxicity
  3. Hyperglycemia
  4. Neurotoxicity (tremor, headache)
  5. Electrolyte abnormalities (increased K, decreased Mg), QT prolongation
27

T/F.

CNIs are famous for causing metabolic disorders. CSA causes more broad metabolic disorders, whereas TAC is more specific (which is why TAC is preferred)

TRUE

28

What are monitoring parameters for

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • Trough levels (dosed Q12, not BID)
  • Serum electrolytes (K, Mg)
  • Blood pressure
  • Blood glucose
29

What's the counseling point for

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • Take consistently with or without food; avoid alcohol
  • Food decreases absorption. Higher fatty food decreases absorption.
30

What's to be cautious about interchangeability of

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • Do not interchange XL to immediate release
31

When to start PO dose vs IV dose?

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • PO IR dose is 3-4 times the IV dose; start oral dosing 8-12 hours after last IV dose
32

What's specific about container of

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • IV is administered as a continuous infusion in a non-PVC container
33

What's DDI of

  • Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
  • CYP450 3A4 and PGP substrate
34

Another drug beside Tacrolimus is___

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
35

What's the brand name for

Cyclosporine modified?

  • Neoral, Gengraf
36

What's the brand name for

Cyclosporine non-modified?

  • Sandimmune
37

The eye drop formulation of Cyclosporine is__?

  • Restasis
38

What's the difference between

  • Neoral, Gengraf vs Sandimmune
  • Neoral, Gengraf: modified, higher bioavailability
  • Sandimmune: non-modified

=> THEY ARE NOT INTERCHANGEABLE

39

What's the BBW for

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
  1. Renal impairment (with high doses)
  2. Increased risk of malignancies and skin cancer
  3. Increased risk of infection
  4. Hypertension
40

What are the AEs of

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
  • Hypertension, hyperglycemia
  • Nephropathy
  • Electrolyte abnormalities (increased K, decreased Mg), QT prolongation
  • Hirsutism
  • Gingival hyperplasia
  • Edema
  • Neurotoxicity
41

What are the monitoring for

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
  • Trough levels (goal 100-400 ng/mL, although nephrotoxicity can occur at any level)
  • Renal function
  • Serum electrolytes (K, Mg)
  • BP
  • Blood glucose
  • Lipid profile
42

What's the counseling for

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)?
  • Avoid alcohol
  • Do not switch brands
43

What's liquid to mix in for?

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)

Do not use a plastic or styrofoam cup with the oral liquid

  • Neoral: dilute with juice (not milk)
  • Sandimmune: dilute with milk or orange juice
44

What to do if you miss a dose >4 h for

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)
  • SKIP this dose and then resume normal dosing schedule.
45

What's DDI for

  • Cyclosporine (modified: Neoral, Gengraf; non-modified: Sandimmune)?
  • CYP3A4 and P-gp substrate
46

What's the typical regimen for transplant?

[1] calcineurin inhibitor + [2] anti-proliferative agent +/- [3] steroids

47

Now we move on to

[2] ANTIPROLIFERATIVE AGENTS

48

What are some

[2] ANTIPROLIFERATIVE AGENTS?

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)
  1. Azathioprine (Azasan, Imuran):
  2. mTOR inhibitors (Everolimus, Sirolimus)
  3. Belatacept (Nulojix)
49

What's the brand for Mycophenolate mofetil?

  • CellCept
50

What's the brand for Mycophenolate acid?

  • Myfortic
51

What's the MoA for

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)
  • Inhibits T-lymphocyte proliferation by altering purine synthesis
52

What's the BBW for

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)
  1. Increased risk of infection
  2. Development of lymphoma/skin malignancies
  3. Congenital malformations and spontaneous abortions when used during pregnancy
53

What's the AEs for

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)

GI upset (DIARRHEA), leukopenia

  • Myfortic is enteric-coated and helps decrease diarrhea!
54

T/F.

CellCept and Myfortic are interchangeable

FALSE.

  • CellCept and Myfortic are NOT interchangeable!!!
55

CellCept IV should be diluted in ___

  • D5W ONLY!
56

What's the counseling for

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)
  • Take on an empty stomach to avoid variability in absorption.
  • Technically, you could take it on a stomach with a hearty meal, but then that would mean you’d have to consistently be eating the same thing in order to make the environment the same for the drug’s pharmacokinetics.
57

What's the DDI for

  • Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic)?

Hint: think or pregnancy

  • Decreased the efficacy of oral contraceptives - use a non-hormonal alternative.
58

What's the brand for

  • Azathioprine?
  • Azasan, Imuran
59

What's BBW for

  • Azathioprine (Azasan, Imuran)?
  • increased risk of neoplasia, hematologic toxicities, mutagenic potential
60

What are ADEs of

  • Azathioprine (Azasan, Imuran)?
  • GI upset (N/V), rash, increased LFTs, bone marrow suppression
61

What population should be careful using

  • Azathioprine (Azasan, Imuran)?
  • Caution with patients who have a genetic deficiency of thiopurine methyltransferase (TPMT) - they will be more sensitive to the myelosuppressive effects!!!
62

What's the DDI with

  • Azathioprine (Azasan, Imuran)?
  • Also metabolized by xanthine oxidase - so sirens should be going off if you see it paired with allopurinol or febuxostat (refresher: they’re xanthine oxidase inhibitors)
  • Febuxostat is a complete no-no; don’t ever use them together!
  • You can use it with allopurinol, but you must decrease azathioprine’s dose by 75%!
63

Can we use Febuxostat with

  • Azathioprine (Azasan, Imuran)?
  • a complete no-no; don’t ever use them together!
64

Can we use Allopurinol with

  • Azathioprine (Azasan, Imuran)?
  • You can use it with allopurinol, but you must decrease azathioprine’s dose by 75%!
65

Besides Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic), Azathioprine (Azasan, Imuran),

what is other

ANTIPROLIFERATIVE AGENTS?

mTOR inhibitors

  • Everolimus (Zortress, Afinitor)
  • Sirolimus (Rapamune)
66

Name 2 mTOR inhibitors?

  1. Everolimus (Zortress, Afinitor)
  2. Sirolimus (Rapamune)
67

What's the brand name for Everolimus?

  • Zortress, Afinitor
68

What's the brand name for Sirolimus?

  • Rapamune
69

What's the MoA of mTOR inhibitors?

  • inhibits T-lymphocyte activation and proliferation
70

What's the BBW for

  • Everolimus (Zortress, Afinitor), Sirolimus (Rapamune)

Similar boxed warnings to previous agents with some exceptions:

  • Everolimus = decrease dose with CSA, risk of renal thrombosis, do not use in heart transplant.
  • Sirolimus = do not use in liver or lung transplant
71

What's the warning for

  • Everolimus (Zortress, Afinitor), Sirolimus (Rapamune)
  • Warnings = hyperlipidemia
72

What's the monitoring and DDI for

  • Everolimus (Zortress, Afinitor), Sirolimus (Rapamune)
  • Monitor trough levels
  • They are CYP3A4 substrates, so watch out for DDIs
73

What are AEs for

  • Everolimus (Zortress, Afinitor)?
  • peripheral edema, hypertension
74

What are AEs for

  • Sirolimus (Rapamune)
  • irreversible pneumonitis/bronchitis/cough
75

Besides Mycophenolate mofetil (CellCept), mycophenolic acid (Myfortic), Azathioprine (Azasan, Imuran), mTOR inhibitors

what is other

ANTIPROLIFERATIVE AGENTS?

  • Belatacept (Nulojix)
76

What is the brand for Belatacept?

  • Nulojix
77

What's the MoA for

  • Belatacept (Nulojix)
  • blocks T-cell stimulation via binding to CD80 and CD86.
78

What's the BBW for

  • Belatacept (Nulojix)
  • increased risk of post-transplant lymphoproliferative disorder (PTLD)
  • Only use this in patients who are EBV (+)!!! (aka they are immune to EBV)
79

What populations can use

  • Belatacept (Nulojix)
  • Only use this in patients who are EBV (+)!!! (aka they are immune to EBV)
80

What's the warning for

  • Belatacept (Nulojix)
  • be sure to treat latent TB infection prior to use!
81

What's the typical regimen for transplant?

[1] calcineurin inhibitor + [2] anti-proliferative agent +/- [3] steroids

82

Now we move on to___

[3] steroids

83

What's the approach with steroid use in transplant patients?

  • Steroids are optional because really, they fuck up your body in so many different ways. If the patient doesn’t need them, taper them off as soon as possible. If they must be on them, use the lowest dose for the shortest period of time.
84

What are the AEs of short-term use of steroid?

MUST KNOW

  • fluid retention, stomach upset, emotional instability (euphoria, mood swings, irritability), insomnia, increased appetite, weight gain, acute rise in blood pressure and blood sugar with high doses
85

What are the AEs of long-term use of steroid?

MUST KNOW

  • adrenal suppression/Cushing’s syndrome, impaired wound healing, hypertension, diabetes, acne, osteoporosis, impaired growth in children
86

In terms of DDI,

CALCINEURIN INHIBITORS (CNIs) have many drug interactions, for___

  • they are CYP3A4 and PGP substrates!
87

In terms of DDI,

CALCINEURIN INHIBITORS (CNIs) should be avoided with___

  • Avoid grapefruit juice and St. John’s wort!
88

In terms of DDI,

  • Mycophenolate decreases the levels of____
  • hormonal drugs
89

In terms of drug monitoring, drugs

  • Highest risk of nephrotoxicity
  • CNIs (TAC, CSA)
90

In terms of drug monitoring, drugs

  • Highest risk of increased blood glucose
  • steroids, CNIs (TAC, CSA)
91

In terms of drug monitoring, drugs

  • Highest risk of increased blood pressure
  • steroids, CNIs (TAC, CSA)
92

In terms of drug monitoring, drugs

  • Highest risk of worsened lipid parameters
  • mTOR inhibitors, steroids, CSA only
93

Transplant recipients are at an increased risk of opportunistic infections such as_____

  1. Pneumocystis jirovecii pneumonia
  2. Candida
  3. CMV
94

Easiest method to prevent induction risk reduction is___

  • HAND WASHING!!!
95

In terms of vaccination,

transplant patients___

  • Live vaccines cannot be given to post-transplant agents, so be sure to vaccine prior to transplant (and the recipient’s close contacts!!) if possible.
96

ORGAN TRANSPLANT COMPLICATIONS:

  1. The medications used to prevent transplant rejection are known to cause _____
  2. There is a high risk for ___so monitor things like blood pressure, blood glucose, cholesterol, and weight closely!
  3. Routine cancer screening is necessary; be sure to use ___ routinely!
  1. metabolic syndrome.
  2. cardiovascular disease,
  3. sunscreen
97

In terms of Acute rejection, how to manage

  • T-cell (cellular) acute rejection?
  • Treat with higher levels of maintenance immunosuppressants
98

In terms of Acute rejection, how to manage

  • B-cell (humoral, antibody) acute rejection?
  • This is much harder to treat, as the antibodies against the graft must be removed, then suppressed from recurring.
  • Options include plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab (Rituxan).