56. Transplant Flashcards
Blood type ___ is considered “universal donor” while blood type ___ is considered “universal receiver”
O
AB
____ is the transplant of an organ or tissue from one individual to another of the space species with a different genotype
Allograft (allogenic transplant)
____ is the transplant of an organ from a genetically identical donor (such as an identical twin)
Isograft
____ is a transplant in the same patient, from one site to another (e.g. autologous stem cell transplant or skin graftin)
Autograft
Prior to any transplant, tissue typing or crossmatching is performed to assess donor-recipient compatibility for ____ and ___
human leukocyte antigen (HLA)
ABO blood group
A commonly used induction drug is ___, an IL-2 receptor antagonist
Basiliximab
MOA basiliximab
IL-2 receptor antagonist
IL-2 receptor is expressed on activated T-lymphocytes and is a critical pathway for activating T-lymphocytes to attack and reject the organ
Note: does not deplete immature T-lymphocytes and therefore cannot be used to treat rejection (only for prevention)
Why is basiliximab only used for prevention of rejection (induction) but not treatment?
Does not deplete immature T-lymphocytes
For patients at higher risk of rejection, what is an alternative to basiliximab?
Antithymocyte globulin (Atgam- Equine) (Thymoglobulin - Rabbit)
Which induction immunosuppression agents can be used for both prevention (induction) and treatment for rejection?
Antithymocyte globulins b/c they deplete both mature and immature T-lymphocytes
T/F: Induction immunosuppression may not be required if the transplant is from an identical twin
True
Boxed warnings for Antithymocyte Globulin
Anaphylaxis can occur; intradermal skin testing recommended prior to 1st dose of Atgam
Must be administered under supervision of a physician with immunosuppressive experience
Side effects for antithymocyte globulin
Infusion related reactions
Others: cytokine release syndrome (fever, chills, pruritis, rash, decreased BP; more common with first dose), infections, leukopenia, thrombocytopenia, chest pain, increased BP, edema
What can lessen infusion-related reactions with antithymocyte globulins?
Premedication - diphenhydramine, APAP, and steroids
Maintenance immunosuppression is generally provided by the combination of _____
Calcineurin inhibitor (CNI) + antiproliferative agent ± steroids
What is the first line CNI agent?
Tacrolimus
Other options: cyclosporine or belatacept
What is the first line antiproliferative agent for most protocols?
Mycophenolate
Other options: azathioprine, mTOR inhibitors (everolimus and sirolimus)
What steroid is typically used in transplant patients?
Prednisone
What is the rationale behind immunosuppression using multiple mechanisms with different drug classes?
Lower toxicity risk and reduce risk of graft rejection
CNI (Cyclosporine, Tacrolimus) MOA
Calcineurin inhibitors, inhibits T-lymphocyte activation
mTORi (everolimus, cirolimus) MOA
mammalian target of rapamycin (mTOR) kinase inhibitors
Inhibits T-lymphocyte activation/proliferation (may be synergistic with CNIs)
Antiproliferative agents (mycophenolate, azathioprine) MOA
Inhibit T- and B-lymphocyte proliferation by altering purine nucleotide synthesis
Basiliximab MOA
IL-2 receptor inhibitor
Betalacept MOA
CD80/86 (on antigen) inhibitor, blocking costimulation with CD28 (on T-lymphocytes)
Boxed warnings for cyclosporine
Nephrotoxicity, increased risk of lymphoma and other malignancies (includes skin cancer)
Increase risk of infection
Can increase BP
Only experience providers should prescribe cyclosporine, cyclosporine (modified - Gengraf/Neoral) has 20-50% greater BA compared to cyclosporine (non-modified - Sandimmune) and cannot be used interchangeably
Which cyclosporine formulations have 20-50% greater bioavailability? Can cyclosporine formulations be used interchangeably?
Gengraf/Neoral (modified) > Sandimmue (non-modified
Cannot be used interchangeably
Side effects for cyclosporine
Increased BP, nephropathy, hyperkalemia, hypomagnesemia, hirsutism, gingival hyperplasia, edema, increase BG, neurotoxicity (tremor, HA, paresthesia), QT prolongation
Others: GI upset, increased TG, viral infections
Monitoring for cyclosporine
Trough levels, serum electrolytes (K and Mg), renal function, LFTs, BP, BG, lipid profile
Drug interactions for cyclosporine
Many drug interactions: CYP3A4 inhibitor and CYP3A4 and P-gp substrate
Inducers of either enzyme (e.g. carbamazepine, nafcillin, rifampin) decrease CNI conc and inhibitors (e.g. azole antifungals, diltiazem, erythromycin) increase CNI conc
For oral liquid of cyclosporine, what types of cups should be avoided?
Plastic or styrofoam cups
Boxed warning for tacrolimus (Prograf)
Increased susceptibility to infection
Possible development of lymphoma
Note: ER tacrolimus (Astagraf XL) a/w increased mortality in female liver transplant recipients
What tacrolimus formulation is a/w increased mortality in female liver transplant recipients?
ER tacrolimus (Astagraf XL)
Side effects for tacrolimus
Increased BP, Increased BG, nephrotoxicity, neurotoxicity (tremor, HA, dizziness, paresthesia), hypo/hyperkalemia, hyperlipidemia, QT prolongation, alopecia
Others: hypomagnesemia, hypo/hyperphosphatemia, edema, chest pain, insomnia, generalized pain, rash/pruritis, diarrhea, abdominal pain, nausea, dyspepsia, anorexia, constipation, UTI, anemia, leukopenia, leukocytosis, thrombocytopenia, elevated liver enzymes, arthralgia
Monitoring for tacrolimus
Specific trough level goal (usually within 3-15 ng/mL) varies based on type of transplant
Serum electrolytes (K, Phos, Mg), renal function, LFTs, BP, BG, lipid profile
Are XL and IR tacrolimus interchangeable?
No
Notes for IV tacrolimus
Continuous infusion
Must use non-PVC bag and tubing
Drug interactions for tacrolimus
Many drug interactions: CYP3A4 and P-gp substrate
Note: tacrolimus absorption is decreased by food
Boxed warnings for Mycophenolate Mofetil (CellCept) // Mycophenolic Acid (Myfortic)
Increased risk of infection, lymphoma and skin malignancies
Increased risk of congenital malformations and spontaneous abortions when used in pregnancy
Side effects for Mycophenolate Mofetil (CellCept) // Mycophenolic Acid (Myfortic)
Diarrhea, GI upset
Others: vomiting, leukopenia, increased/decreased BP, edema, tachycardia, pain, increased BG, hypo/hyperkalemia, hypomagnesemia, hypocalcemia, hypercholesterolemia, tremor, acne, infections
Is CellCept and Myfortic interchangeable?
No (differences in absorption CellCept 500mg = ~Myfortic 360mg)
Which mycophenolate formulation is enteric coated to decrease diarrhea?
Myfortic (Mycophenolic Acid) (1% absolute diff with CellCept vs Myfortic)
CellCept IV is stable in ____ only.
D5W
What is the drug interaction between mycophenolate and oral contraceptives?
Mycophenolate decreases efficacy of oral contraceptives
Warning for Azathioprine (Azasan, Imuran)
Patients with deficiency of TPMT are at higher risk for myelosuppression and may require lower dose
GI (severe N/G/D), hematologic (leukopenia, thrombocytopenia, anemia) and hepatotoxicity
Which mTOR is not recommended in heart transplant? Liver or lung transplant?
Heart = Everolimus (Zortress)
Liver/Lung = Sirolimus (Rapamune)
Warnings for everolimus (Zortress)
HLD, impaired wound healing
Others: Hypertriglyceridemia, angioedemia, fluid accumulation, pneumonitis (d/c if this develops), proteinuria, anemia, lymphocytopenia, thrombocytopenia, new-onset DM, male infertility
Side effects for everolimus (Zortress)
Peripheral edema, increased BP, risk of renal and hepatic artery thrombosis (do NOT use within 30 days of transplant)
Others: N/V/D, constipation, HA, increased BG, fatigue, fever, rash/pruritus, xeroderma, acne, onychoclasis (nail disease), abdominal discomfort, stomatitis, dysgeusia, weight loss, dry mouth
Monitoring for everolimus (Zortress)
Trough levels
Others: renal function, LFTs, lipids, BG, BP, CBC, s/sx infection
Drug interactions for everolimus (Zortress)
Many - CYP3A4 and P-gp substrate
Warnings for sirolimus (Rapamune)
Impaired wound healing, HLD
Others: angioedema, fluid accumulation, decline in renal fxn, latent viral infections, increased risk of hemolytic uremic syndrome when used with CNI
Side effects for sirolimus (Rapamune)
Irreversible pneumonitis/bronchitis/cough (d/c if this develops)
Increased BG, peripheral edema
Other: increased BP, HA, pain, insomnia, acne, constipation, abdominal pain, diarrhea, nausea, anemia, thrombocytopenia, arthralgia
Monitoring for sirolimus (Rapamune)
Trough levels
Others: renal function, LFTs, lipids, BG, BP, CBC, s/sx infection
T/F: sirolimus tabs and oral solution are bioequivalent
False - not bioequivalent
Drug interactions for sirolimus
Numerous drug interactions - CYP3A4 and P-gp substrates
Short-term side effects of prednisone
Fluid retention, stomach upset, emotional instability (euphoria, mood swings, irritability), insomnia, increased appetite, weight gain, acute rise in BG and BP with high doses
Longer-term side effects of prednisone
Adrenal suppression/Cushing’s syndrome, impaired wound healing, increased BP, DM, acne, osteoporosis, impaired growth in children
Boxed warnings for Belatacept (Bulojix)
Increased risk of post-transplant lymphoproliferative disorder (PTLD) (highest risk in pts w/o immunity to Epstein-Barr Virus (EBV)
Use in EBV seropositive patients only
Which transplant med should be used in EBV seropositive pts only?
Belatacept (Bulojix)
Warnings for Belatacept
Increased risk for TB - test for latent TB prior to initiation and treat latent TB prior to use
Which transplant drugs are used for induction?
Basiliximab (IL-2 receptor antagonist)
Antithymocyte globulin in pts at higher risk of rejection
High dose IV steroids
Which transplant drugs are used for maintenance?
CNI (tacrolimus (primarily) or cyclosporine) // belatacept as an alt to CNI
Antiproliferative agents (mycophenolate or azathioprine) or mTORi (everolimus, sirolimus)
Steroids at lower or tapering doses
Which transplant med absorption is decreased by food?
Tacrolimus
Azathioprine is metabolized by xanthine oxidase. Avoid using azathioprine with xanthine oxidase inhibitors (____or ___)
Allopurinol or febuxostat
Which transplant meds should be avoided with grapefruit juice and St. John’s wort
CNIs
Which transplants meds should providers use caution with additive drugs that are nephrotoxic?
CNIs
Which transplants meds should providers use caution with additive drugs that raise BG?
Steroids, CNIs, mTORi
Which transplants meds should providers use caution with additive drugs that worsen lipids ?
mTORi, steroids, cyclosporine
Which transplants meds should providers use caution with additive drugs that increase BP ?
Steroids and CNIs
What are common boxed warnings that are found for many transplant meds?
Infection risk
Cancer risk
“Only experience prescribers”
All transplant recipients must self-monitor for s/sx infection. What are some things you can counsel on?
Fever 100.4ºF (38ºC) or higher (lower if elderly), chills
Cough, more sputum or change in color, sore throat
Pain with passing urine, ear, or sinus pain
Mouth sores or wound that does not heal
Acute rejection of a transplanted oran arises from either ___ or ___ mediated mechanisms. Both types can occur simultaneously. Distinguishing the type of rejection via ___ is essential to determine treatmet
T-cell (cellular)
B-cell (humoral or antibody)
biopsy
An initial approach to treating acute cellular rejection (ACR) is the administration of ____ and increased levels of maintenance immunosuppression
High-dose steroids
Is acute cellular rejection (ACR) or antibody-mediated rejection (AMR) more difficult to treat?
AMR - antibodies against the graft must be removed and then suppressed from recurring (by plasmapheresis and use of IVIG + rituximab)
Important vaccines for transplant recipients
Influenza (inactive, not live) annually
Pneumococcal vaccine in adults ≥19 yo (either PCV20 x1 or PCV15 x1 + PPSV23 x1 ≥ 8 weeks late)
Varicella (vaccinate pre-transplant + close contacts; if vaccinated household contact develops a rash avoid contact + contact physician; if transplant pt develops rash, must be seen right away)
What kind of cancer is common following a transplant and what do you recommend?
Skin cancer
Sunscreen must be used routinely
T/F: transplant meds can cause metabolic syndrome
True
What is the frequency for XL or XR tacrolimus formulations?
every 12 hours or once daily in the morning on empty stomach
Important things to note when giving cyclosporin oral solution
Use syringe provided
Do NOT rinse syringe before/after use
Use compatible diluent (e.g. orange juice) at room temp
Do NOT administer from plastic/styrofoam cup, use glass
Administer/drink immediately, rinse container with extra diluent to ensure total dose is take
