Related | Abdominal Transplant Immunosuppression Management - Adult - Inpatient/Ambulatory
Abdominal Transplant Immunosuppression
Management - Adult - Inpatient/Ambulatory
Consensus Care Guideline
Population/Problem:
The information presented in this document is intended to guide the use of immunosuppressive
medications in adult patients who have a history of an abdominal organ transplant (i.e. kidney,
liver, and pancreas). Guidance is provided to use immunosuppressive medications safely and
effectively in the inpatient and outpatient settings. Guidance is provided for the use of
azathioprine, belatacept, cyclosporine, everolimus, mycophenolate, prednisone, sirolimus, and
tacrolimus. Guidance is also provided for the use of alemtuzumab, basiliximab,
dexamethasone, IVIG, rituximab, and thymoglobulin in the setting of renal transplant induction,
desensitization, and rejection.
Information is provided for dosing, target blood levels, common drug interactions, monitoring,
and common adverse effects.1-5
The guideline assists in the decision making of physicians, mid-level providers, pharmacists,
and nursing staff.
Recommendations:
UW Health recommendations are based on long-standing experience with clinical care. The
recommendations are supported by very low quality evidence.
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Disclaimer
Consensus care models assist clinicians by providing a framework for the evaluation and
treatment of patients. This guideline outlines the preferred approach for most patients. It is not
intended to replace a clinician’s judgment or to establish a protocol for all patients. It is
understood that some patients will not fit the clinical condition contemplated by a guideline and
that a guideline will rarely establish the only appropriate approach to a problem.
Content Expert(s):
David Hager, PharmD – Director, Pharmacy Clinical Services
Phone Number: (608) 890-8993
Email Address: dhager@uwhealth.org
Contact for Changes:
Philip Trapskin, PharmD – Director, Pharmacy Policy, Safety, Compliance and Informatics
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org
Guideline Author(s):
Melissa Durst, PharmD – Pharmacy Transplant Services
Workgroup Members:
Daniel Felix, PharmD
Jillian Fose, PharmD
David Hager, PharmD
Anthony Hennes, PharmD
Kimberly Holdener, PharmD
Mei Jorgenson, PharmD
Jamie Myers, RN
Nancy Radke, RN
Josh Wiegel, PharmD
Reviewer(s):
Dixon Kaufman, MD
Arjang Djamali, MD
Dave Foley, MD
Didier Mandelbrot, MD
Jon Odorico, MD
John Rice, MD
Committee Approval(s):
Pharmacy & Therapeutics Committee (06/17/21)
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Table 1. GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate
We are quite confident that the effect in the study is close to the true effect, but
it is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.
Table 2. GRADE Ratings for Recommendations for or Against Practice
Strong (S)
Generally, should be performed (i.e., the net benefit of the treatment is
clear, patient values and circumstances are unlikely to affect the decision.)
Conditional (C)
May be reasonable to perform (i.e., may be conditional upon patient values
and preferences, the resources available, or the setting in which the
intervention will be implemented.)
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Collateral Tools & Resources
The following collateral tools and resources support staff execution and performance of the
evidence-based model recommendations in everyday clinical practice.
Metrics
Relevant metrics include graft survival, rejection rates and rates of opportunistic infections.
Order Sets & Smart Sets
•
•
•
•
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References-
1. Kidney Disease: Improving Global Outcomes Transplant Work G. KDIGO clinical
practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9
Suppl 3:S1-155.
2. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin
inhibitors in renal transplantation. N Engl J Med. 2007;357(25):2562-2575.
3. Hanaway MJ, Woodle ES, Mulgaonkar S, et al. Alemtuzumab induction in renal
transplantation. N Engl J Med. 2011;364(20):1909-1919.
4. Lucey MR, Terrault N, Ojo L, et al. Long-term management of the successful adult liver
transplant: 2012 practice guideline by the American Association for the Study of Liver
Diseases and the American Society of Transplantation. Liver Transpl. 2013;19(1):3-26.
5. Scott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus: a further update of its use in
the management of organ transplantation. Drugs. 2003;63(12):1247-1297.
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Tacrolimus – liver transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • Initiation of tacrolimus should on post-
operative day 1 after transplant (UW Health,
Very Low, Conditional)
Dosing
(initial)
Standard dosing Fixed dose 2 mg by mouth twice daily • Capsules and suspension may be taken with or
without food. Since the presence of food affects
the bioavailability of tacrolimus, if taken with
food, it should be taken consistently the same
way each time. (UW Health, Very Low,
Conditional)
• Tacrolimus may be given sublingually in patients
unable to adequately absorb enteral
formulations or in those unable to take oral. If a
patient is being transitioned to tacrolimus
sublingual from tacrolimus IR, each dose should
be divided by 2 and given sublingually. (UW
Health, Very Low, Conditional)
• Use of IV should be considered rare and risky
and only considered in the inpatient setting.
Only after discussion with an experienced
transplant pharmacist and the faculty of record
can it be considered. Conversion from IV to oral
tacrolimus is recommended as soon as enteral
therapy can be tolerated to minimize risk of
anaphylactic reactions that occur with
injectables containing castor oil derivatives.
(UW Health, Very Low, Conditional)
• LCP-Tacrolimus (Envarsus®) may be utilized in
patients with documented intolerable adverse
effects with tacrolimus IR or who are unable to
obtain a therapeutic drug concentration with
the IR formulation. If a patient is being
transitioned to LCP-tacrolimus from tacrolimus
IR, the total daily dose should be multiplied by
0.8, then rounded to the nearest tablet size.
Astagraf, Envarsus, and Prograf are not
interchangeable (UW Health, Very Low,
Conditional)
Increased sensitivity (on CYP3A4 inhibitor - see list
below)
Fixed dose 1 mg by mouth twice daily
Drug-drug
Interactions
(not an all-
inclusive
list)
Increases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Adjust tacrolimus dose empirically for the
following CYP4 inhibitors:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor tacrolimus levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Monitor tacrolimus levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Autoimmune
disease and
not on MPA
NOT
autoimmune
OR on MPA
0-3 months: 8-10 ng/mL 5-7 ng/mL
3-6 months: 8-10 ng/mL 5-7ng/mL
6-12 months: 6-8 ng/mL 3-5 ng/mL
>12 months: 4-6 ng/mL 2-5 ng/mL
*Above trough goals are general guidance, and
immunosuppression should be tailored to
patient’s immunologic risk and tolerance of
medications*
Below/Above
Target
>50% Adjust dose by 25-50%*
<50% Adjust dose by 25%
*Holding doses may be necessary
Laboratory Monitoring:
Tacrolimus (trough), potassium, and creatinine
Inpatient: Daily
Outpatient:
Day after discharge Frequency
0-30 Twice weekly
31-90 Not less than weekly
91-180 Not less than twice
monthly
181-365 Not less than once
monthly
Modify as Needed on a Patient-by-Patient basis:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
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Adverse
effects
Acute kidney injury • Assess tacrolimus trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease tacrolimus dose if trough is <4 ng/mL above goal
o Hold tacrolimus if trough >5 ng/mL above goal and consider increasing current prednisone
dose
• Consult transplant physician regarding further work up elevated creatinine
Neurological symptoms (tremor, headache) • Assess tacrolimus trough level for correlation with tremors or headache
• If trough level is above goal, adjust tacrolimus dose and follow up with patient
• If trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week to assess continued symptoms and trend severity
• If adverse effects are persistent, not improving, or interfering with daily activities and there is no
other known cause:
• Consult the transplant physician to consider splitting IR tacrolimus to three times daily or
converting the patient to LCP-tacrolimus or cyclosporine
• Addition of a low dose propranolol may also be considered if heart rate >60 BPM, systolic blood
pressure >120 mmHg, and patient is not already on a beta blocker
New onset diabetes after transplantation
(NODAT)
Diagnosis (2 of the following)
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• Hba1c > 7.0% for more than 2 months
• No tacrolimus dose adjustment is recommended
• Consult diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health
Organization (WHO) and American Diabetes Association (ADA) that develops for the first time after
transplantation
• Continue planned discontinuation of glucocorticoids by 2 months
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent):
o Consult transplant physician and consider reassessment of steroid dosing or conversion to LCP-
tacrolimus
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Cyclosporine – liver transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • The initiation of cyclosporine should start post-
operative day 1 after transplant (UW Health, Very
Low, Conditional)
Dosing
(initial)
Standard dosing Fixed dose 150 mg by mouth twice daily • Neoral/Gengraf (cyclosporine modified) and
Sandimmune (cyclosporine non-modified) are not
bioequivalent and cannot be used
interchangeably (UW Health, Very Low,
Conditional)
• Cyclosporine modified is preferred over
cyclosporine non-modified (UW Health, Very Low,
Conditional)
• Capsules and suspension may be taken with or
without food. However, since the presence of
food affects the bioavailability of cyclosporine, if
taken with food, it should be taken consistently
the same way each time. (UW Health, Very Low,
Conditional)
Increased sensitivity (on CYP3A4 inhibitor - see list
below)
Fixed dose 100 mg by mouth twice daily
Drug-Drug
Interactions
(not an all-
inclusive
list)
Increases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Adjust cyclosporine dose empirically for the
following CYP4 inhibitors:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor cyclosporine levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Monitor cyclosporine levels and adjust as
needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Autoimmune
disease and
not on MPA
NOT
autoimmune
OR on MPA
0-3 mo: 150-200 ng/mL 125-175 ng/mL
3-6 mo: 125-150 ng/mL 125-150 ng/mL
6-12 mo: 100-125 ng/mL 75-100 ng/mL
>12 mo: 100 ng/mL 50-75 ng/mL
*Above trough goals are general guidance, and
immunosuppression should be tailored to
patient’s immunologic risk and tolerance of
medications*
Below/Above
Target
>50% Adjust dose 25% to 50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Laboratory Monitoring:
Cyclosporine (trough), potassium, and
creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-30 Twice weekly
31-90 Not less than weekly
91-180 Not less than twice
monthly
181-365 Not less than once
monthly
Modify as Needed on a Patient-by-Patient
basis:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
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Adverse
effects
Acute kidney injury • Assess cyclosporine trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease cyclosporine dose if trough is <50 ng/mL above goal
o Hold cyclosporine if trough >50 ng/mL above goal and consider increasing current prednisone
dose
• Consult transplant physician regarding further work up elevated creatinine
Neurological symptoms (tremor, headache) • Assess cyclosporine trough level for correlation with tremors or headache
• If trough level is above goal, adjust cyclosporine dose and follow up with patient
• If trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week to assess continued symptoms and trend severity
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to LCP-tacrolimus
o Addition of a low dose propranolol may also be considered if heart rate >60 BPM, systolic blood
pressure >120 mmHg, and patient is not already on a beta blocker
New onset diabetes after transplantation
(NODAT)
Diagnosis (2 of the following)
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• Hba1c > 7.0% for more than 2 months
• No cyclosporine dose adjustment is recommended
• Consult diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health Organization
(WHO) and American Diabetes Association (ADA) that develops for the first time after transplantation
• Continue planned discontinuation of glucocorticoids by 60 days
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent):
• Consult transplant physician and consider reassessment of steroid dosing or conversion to other
immunosuppressant
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Mycophenolate – liver transplant
Recommendation Notes/Evidence
Initiation Post-operative day 0 • Full dose mycophenolic acid is the preferred anti-
proliferative medication used for liver transplant
patients (UW Health, Very Low, Conditional)
• IV mycophenolate mofetil is indicated if the patient
has an acute condition that affects gastrointestinal
absorption (i.e., GI bleed or obstruction,
malabsorption syndromes, severe diarrhea or
severe vomiting) (UW Health, Very Low,
Conditional)
• Mycophenolate mofetil suspension is utilized for
patients receiving medications via nasogastric or
orogastric tube
Dosing
(initial)
Mycophenolate mofetil
1000 mg IV x 1 dose POD0
1000 mg IV twice daily x 4 doses POD1-2
Mycophenolate sodium 720 mg PO twice daily and after POD3
Drug-drug
interactions
(not an all-
inclusive
list)
Medications that decrease mycophenolate concentration
• Cyclosporine
• Bile acid sequestrants
Mycophenolate decreases concentration of estrogen derivatives. Women of childbearing potential
who are receiving mycophenolate mofetil should consider using an alternative and/or additional
form of contraception.
*Check Lexicomp for dose adjustments*
Target
levels
Labs Laboratory Monitoring:
• Lab monitoring of MPA levels is not recommended to assess for toxicity or efficacy
• If levels are requested, they are only appropriate for mycophenolate mofetil and should be
drawn as a trough
Goal MPA Trough
CsA or TAC based regimens 1.0-3.5 mg/L
• MPA AUC is a better predictor of clinical events
than MPA trough. Trough levels are poorly
correlated with AUC and are not recommended
(UW Health, Very Low, Conditional)
• Levels may be utilized for assessing safety; not
recommended to assess efficacy
Adverse
effects
Diarrhea
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
o Consider colonoscopy if diarrhea persists and all
stool studies are negative
*In any patient post-liver transplant with diarrhea in the
first 6 months, consider graft-versus-host disease
• If diarrhea work-up is negative for an infectious cause of diarrhea and it is affecting activities of daily
living or the patient is having limited and/or decreased oral intake:
o Decrease mycophenolate by 25% and increase dosing frequency (ex. 720 mg BID → 360 mg
TID)
▪ If fails, decrease mycophenolate by 50%
o Follow up with patient in 1 week to assess continued symptoms and trend severity
o If dose is decreased to 180 mg twice daily (MYF) or 250 mg twice daily (MMF) consult
provider to determine if other immunosuppression needs to be adjusted
o Consider adding the following:
▪ Add loperamide (Imodium®) 2 mg as needed after each loose stool (max dose: 16
mg daily)
▪ Diphenoxylate/atropine (Lomotil®) 5 mg four times daily as needed (max dose: 20
mg/day)
▪ Psyllium fiber (Metamucil®) 3.4 g daily as needed
• If patient is continuing to have symptoms despite lowering immunosuppression, discuss with
transplant provider
Leukopenia • Consult transplant physician regarding further work up leukopenia
• Adjust dose based on following recommendations:
o WBC 2-4 x 109/L: Could consider decrease in total daily dose by 50%
o WBC <2 x 109/L: Hold doses until leukopenia resolves
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• Consider dose modifications or discontinuations of other medications that may cause leukopenia
• If leukopenia persists despite medication changes, consider graft-versus-host disease
Heartburn/nausea • Counsel patient on taking MYF or MMF with food if not already doing so
• Convert from MMF to MYF if only upper GI complaints (heartburn, nausea)
• Add calcium carbonate as needed, or the addition of an H2RA or PPI if not already on
• If symptoms continue following 1 week of daily therapy increase H2RA or PPI dose to twice daily,
reassess in 1 week
• If symptoms persist for ≥1 week, consider EGD to rule out infection vs. ulceration
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Azathioprine – liver transplant
Recommendation Notes/Evidence
Initiation Failure to tolerate mycophenolate • Azathioprine is recommended for use in patients
unable to tolerate adverse effects of mycophenolate
(UW Health, Very Low, Conditional)
Dosing
(initial)
1-3 mg/kg by mouth daily rounded to nearest 25 mg dose • Azathioprine is considered to be less effective than
MPA in preventing rejection. Prior to initiating
azathioprine, consider the total immunosuppression
for the patient and timing out from transplant
• Azathioprine 50 mg tablets should be prescribed as
azathioprine 75 and 100 mg tablets are not available
as generic and are more expensive
Drug-drug
interactions
(not an all-
inclusive
list)
Increases azathioprine concentration:
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Febuxostat
Adjust azathioprine dose empirically:
• Allopurinol
Labs Laboratory Monitoring:
• Monitor CBC with differential and platelets weekly during first month, twice monthly for
months 2 and 3, then monthly thereafter; monitor more frequently with dose modifications
• Monitor LFTs every 3 months while on treatment
• There is no recommended azathioprine level for monitoring purposes. However, if toxicity is
suspected, check thiopurine methyltransferase (TPMT)
Adverse
effects
Leukopenia • Consult transplant provider if WBC <3 and consider checking thiopurine methyltransferase (TPMT)
Gastrointestinal
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
Consider colonoscopy if diarrhea persists and all stool
studies are negative
• See diarrhea work-up algorithm
Pancreatitis • Consult transplant provider if suspected based on patient symptoms
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Sirolimus/everolimus – liver transplant
Recommendations Notes/Evidence
Initiation For use in patients with:
• CNI toxicity
• Skin cancer
• Recurrent hepatocellular carcinoma
• Renal dysfunction
Quadruple therapy
• Sirolimus/everolimus may impair or delay wound healing,
and should be used with caution in the peri-surgical
period (UW Health, Very Low, Conditional)
• Sirolimus should not be used within 30 days of liver
transplant due to risk of hepatic artery thrombosis (UW
Health, Very Low, Conditional)
• May be indicated for use in patients with recurrent skin
cancers as a replacement for azathioprine, MPA, or CNIs
(UW Health, Very Low, Conditional)
Dosing (initial) Sirolimus 2 mg by mouth once daily
Everolimus 0.75 mg by mouth twice daily
Drug-drug
interactions (not
an all-inclusive
list)
Increase mTOR concentration (not an all-
inclusive list):
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Posaconazole
• Voriconazole
• Ritonavir
Monitor mTOR levels and adjust as needed:
• Fluconazole
• Ritonavir
• Letermovir
• Clarithromycin
• Erythromycin
Decrease mTOR concentration (not an all-
inclusive list)
*Check Lexicomp for dose adjustments*
Monitor mTOR levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Goal Trough Levels (Siro/Evr+FK) Goal Trough Levels (Siro/Evr+MPA)
0-3 mo: Siro/Evr: 4-7 ng/mL; FK: 5-7 ng/mL Siro/Evr: 8-10 ng/mL
3-6 mo: Siro/Evr: 4-7 ng/mL; FK: 5-7 ng/mL Siro/Evr: 8-10 ng/mL
6-12 mo: Siro/Evr: 3-5 ng/mL; FK: 3-5 ng/mL Siro/Evr: 5-8 ng/mL
>12 mo: Siro/Evr: 3-5 ng/mL; FK: 3-5 ng/mL Siro/Evr: 5-8 ng/mL
*Above trough goals are general guidance, and immunosuppression should be tailored to
patient’s immunologic risk and tolerance of medications*
Laboratory Monitoring:
• Recommended monitoring trough level once weekly upon initiation and with any dose
changes
• When target trough level has been attained, recommend monitoring levels once monthly
• Monitor fasting lipids profile annually, proteinuria at 6 months and then annually post-
transplant, and LFTs and CBC while on therapy.
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Adverse Effects Proteinuria • Consider administration of angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II receptor
antagonists and reducing mTOR levels
Mouth ulcers • Development of mouth ulcers seems to be dose-related because they usually appear after the loading
dose and often improve after a dose reduction
• Addition of a high-potency topical steroid may be considered
Hyperlipidemia • Follow current guidelines for management (diet, exercise, lipid lowering agents)
• Immunosuppressive strategies minimizing doses of mTORs, CNIs, or corticosteroids may help in
controlling hyperlipidemia
Leukopenia • Consider dose reduction or temporary drug suspension if appropriate
Thrombocytopenia • Consider dose reduction or temporary drug suspension if appropriate
Anemia • Consider dose reduction or temporary drug suspension if appropriate
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Prednisone – liver transplant
Recommendations Notes/Evidence
Initiation Post-operative day 5 following dexamethasone taper • Prednisone 10 mg twice daily will be
started on POD 5 following
dexamethasone taper and may be
continued on discharge
Dosing
(initial)
Standard steroid taper
• Prednisone taper should occur following
POD5
• Assessment for prednisone taper should
occur at 3-4 weeks post-operatively for
patients without autoimmune disease
• Factors that may influence the duration of
prednisone taper:
o Current and historical CNI levels
o Current and historical MPA dosing
o Current liver function
o Episodes of rejection
o Perceived rejection and infection risk
Dexamethasone 100 mg POD0
50 mg POD1
25 mg POD2
12 mg POD3
6 mg POD4
Prednisone 10 mg BID POD5
Without
autoimmune
disease
Decrease by 5 mg every 2 weeks until gone
With
autoimmune
disease
Decrease by 5 mg every 2 weeks to a dose
of 5 mg daily
• Prednisone doses should be split to
twice daily dosing for patients requiring
insulin for glucose control (UW Health,
Very Low, Conditional)
• Patient should be off prednisone by 2
months post-transplant and
maintained on tacrolimus and
mycophenolate but is based on
provider discretion
• For patients on doses higher than 20
mg daily for anticipated duration of
greater than 2 weeks, PJP prophylaxis
should be initiated
Labs Laboratory Monitoring:
Glucose, bone mineral density
Adverse
effects
Hyperglycemia • Prednisone doses should be split to twice daily dosing for patients requiring insulin for glucose control
Heartburn/reflux • Start a proton pump inhibitor (PPI) at time of transplant
• If a patient complains of heartburn on daily dosing of the PPI, frequency may be increased to twice daily
(pending renal function)
• Discontinue PPI in patients with no history of heartburn/gastroesophageal reflux disease (GERD) prior to
transplant if prednisone is discontinued
Osteoporosis • Recommend calcium 1200 mg daily (based on elemental calcium dosing)
• Recommend vitamin D 2000 units daily
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Tacrolimus – pancreas transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • Initiation of tacrolimus should start before or at
the time of transplant, rather than delayed until
the onset of graft function (UW Health, Very
Low, Conditional)
Dosing
(initial)
Non-African American NPO - 1 mg twice daily • Capsules and suspension may be taken with or
without food. Since the presence of food affects
the bioavailability of tacrolimus, if taken with
food, it should be taken consistently the same
way each time. (UW Health, Very Low,
Conditional)
• Tacrolimus may be given sublingually in patients
unable to adequately absorb enteral
formulations or in those unable to take oral. If a
patient is being transitioned to tacrolimus
sublingual from tacrolimus IR, each dose should
be divided by 2 and given sublingually. (UW
Health, Very Low, Conditional)
• Use of IV tacrolimus should be considered rare
and risky. Only after discussion with an
experienced transplant pharmacist and the
faculty of record can it be considered for
patients unable to adequately absorb enteral
formulationsa,b. Conversion from IV to oral
tacrolimus is recommended as soon as enteral
therapy can be tolerated to minimize risk of
anaphylactic reactions that occur with
injectables containing castor oil derivatives (UW
Health, Very Low, Conditional). Transplant
Pharmacist should be consulted to assist in
dosing and monitoring therapeutic levels
• LCP-Tacrolimus (Envarsus®) may be utilized in
patients with documented intolerable adverse
effects with tacrolimus IR or who are unable to
obtain a therapeutic drug concentration with
the IR formulation. If a patient is being
transitioned to LCP-tacrolimus from tacrolimus
IR, the total daily dose should be multiplied by
0.8, then rounded to the nearest capsule size.
Astagraf, Envarsus, and Prograf are not
interchangeable (UW Health, Very Low,
Conditional)
PO - 0.025 mg/kg (use ABW) by mouth twice
daily, rounded to the nearest capsule size
African American NPO - 2 mg twice daily
PO - 0.05 mg/kg (use ABW) by mouth twice daily,
rounded to the nearest capsule size
Drug-drug
Interactions
(not an all-
inclusive list)
Increases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Adjust tacrolimus dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor tacrolimus levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Monitor tacrolimus levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
• Octreotide
Target levels
Dose
Adjustments
Labs
Concurrent use of mycophenolate +/- prednisone
Tacrolimus goals may differ if patient is not on
mycophenolate +/- prednisone regimen. Goal
level should be discussed with provider.
Target TAC Level
SPK* PTA/PAK
0-3 months: 8-10 ng/mL 9-11 ng/mL
3-12
months:
8-10 ng/mL 9-11 ng/mL
1-3 years: 6-8 ng/mL 7-9 ng/mL
>3 years: Per provider discretion
*Follow PTA/PAK goals if secondary SPK or MFI ≥ 100
Below/Above
Target
>50%* Adjust dose by 25-50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Laboratory Monitoring:
Tacrolimus (trough), potassium, and creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-60 Not less than twice weekly
60-90 Not less than once weekly
91-120 Not less than twice monthly
120-360 Not less than once monthly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
aScott LJ, McKeage K, Keam SJ, Plosker GL. Tacrolimus a further update of its use in management of organ transplantation. Drugs. 2003;63(12):1247-1297.
bPrograf (tacrolimus) capsules/injection. Package insert. Astellas Pharma US, Inc; 2012.
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Adverse
effects
Acute kidney injury • Assess tacrolimus trough level for correlation with elevated creatinine
• If all other causes are ruled out and an elevated level is found, discuss with physician the
appropriateness of dose reduction
• Consult transplant physician regarding further work up elevated creatinine
Neurological symptoms (tremor, headache) • Assess tacrolimus trough level for correlation with tremors or headache
• If trough level is above goal, adjust tacrolimus dose and follow up with patient
• If trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week to assess continued symptoms and trend severity
• If adverse effects are persistent, not improving, or interfering with daily activities and there is no
other known cause:
o Consult the transplant physician to consider splitting IR tacrolimus to three times daily,
converting the patient to LCP-tacrolimus, belatacept, or cyclosporine, or refer to primary
care provider for supportive therapy, such as addition of low dose beta blocker
(propranolol)
Post-transplant diabetes mellitus (PTDM)
Diagnosis (2 of the following)
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• Hba1c > 7.0% for more than 2 months
• Diagnosis of Post-transplant diabetes mellitus (PTDM) is defined by the World Health Organization
(WHO) and American Diabetes Association (ADA) that develops for the first time after
transplantation
• Consult transplant physician regarding further work up of hyperglycemia
• Consult transplant physician and consider converting the patient to cyclosporine, reassessment of
steroid dosing, conversion to LCP-tacrolimus or belatacept with lowered tacrolimus goals
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Cyclosporine – pancreas transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • The initiation of cyclosporine should start before
or at the time of transplantation, rather than
delayed until the onset of graft function (UW
Health, Very Low, Conditional)
• Tacrolimus is the preferred therapy in pancreas
transplant (UW Health, Very Low, Conditional)
• If cyclosporine was necessary, cyclosporine
modified should be used to prevent variability in
absorption. Sandimmune and other non-
modified products should not be used in the
pancreas transplant population (UW Health,
Very Low, Conditional)
Dosing
(initial)
Decreased sensitivity (African-American, >80kg) Fixed dose 150 mg by mouth twice daily • Neoral/Gengraf (cyclosporine modified) and
Sandimmune (cyclosporine non-modified) are
not bioequivalent and cannot be used
interchangeably (UW Health, Very Low,
Conditional)
• Cyclosporine modified is preferred over
cyclosporine non-modified (UW Health, Very
Low, Conditional)
• Capsules and suspension may be taken with or
without food. However, since the presence of
food affects the bioavailability of cyclosporine, if
taken with food, it should be taken consistently
the same way each time. (UW Health, Very Low,
Conditional)
Increased sensitivity (NPO, <80kg) Fixed dose 100 mg by mouth twice daily
Drug-Drug
Interactions
(not an all-
inclusive
list)
Increases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Adjust cyclosporine dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor cyclosporine levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Monitor cyclosporine levels and adjust as
needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Below/Above
Target
>50% Adjust dose 25% to 50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Goal CSA Level
0-3 months: 200-300 ng/mL
3-6 months: 150-250 ng/mL
>6 months: 100-200 ng/mL
Laboratory Monitoring:
Cyclosporine (trough), potassium, and
creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-60 Not less than twice weekly
60-90 Not less than once weekly
91-180 Not less than twice monthly
181-240 Not less than once monthly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse
effects
Acute kidney injury • Assess cyclosporine trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease cyclosporine dose if trough is <50 ng/mL above goal
o Hold cyclosporine if trough >50 ng/mL above goal and consider increasing current prednisone
dose
• Consult transplant physician regarding further work up elevated creatinine
Neurological symptoms (tremor, headache) • Assess cyclosporine trough level for correlation with tremors or headache
• If trough level is above goal, adjust cyclosporine dose and follow up with patient
• If trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week to assess continued symptoms and trend severity
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to LCP-tacrolimus,
belatacept, or refer to primary care provider for supportive therapy, such as addition of low
dose beta blocker (propranolol)
Post-transplant diabetes mellitus (PTDM)
Diagnosis (2 of the following)
• Sx of DM + casual PG concentrations ≥200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• Hba1c > 7.0% for more than 2 months
• No cyclosporine dose adjustment is recommended
• Consider consulting diabetes management & nutrition services
• Diagnosis of Post-transplant diabetes mellitus (PTDM) is defined by the World Health Organization
(WHO) and American Diabetes Association (ADA) that develops for the first time after transplantation
• Consult transplant physician regarding further work up of hyperglycemia
o Consult transplant physician and consider reassessment of steroid dosing, or conversion to
belatacept with lowered tacrolimus goals
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Mycophenolate – pancreas transplant
Recommendation Notes/Evidence
Initiation Post-operative day 1 • Full dose mycophenolic acid is the preferred anti-
proliferative medication used for PTA, PAK, and SPK
transplant patients (UW Health, Very Low, Conditional)
• IV mycophenolate mofetil is administered for the first 4
doses after transplant and may also be indicated if the
patient has an acute condition that affects
gastrointestinal absorption (i.e., GI bleed or
obstruction, malabsorption syndromes, severe diarrhea
or severe vomiting) (UW Health, Very Low, Conditional)
• Mycophenolate mofetil suspension is utilized for
patients receiving medications via nasogastric or
orogastric tube
Dosing
(initial)
Mycophenolate mofetil
1000 mg IV x 1 dose POD0
1000 mg IV twice daily x 4 doses POD1-2
Mycophenolate sodium 720 mg PO twice daily POD3
*Note: if sum MFI 1000-4000 or patient is African American, consider 720 mg TID on
POD3 and discharge
Drug-drug
interactions
(not an all-
inclusive
list)
Decreases mycophenolate concentration
*Check Lexicomp for dose adjustments*
• Cyclosporine
• Bile acid sequestrants
Mycophenolate decreases concentration of estrogen derivatives. Women of childbearing potential
who are receiving mycophenolate mofetil should consider using an alternative and/or additional
form of contraception.
Target
levels
Labs
Goal MPA Troughc
CsA based
regimens:
1.3-2.8 mg/L
TAC based
regimens:
1.9-2.8 mg/L
Laboratory Monitoring:
• Lab monitoring of MPA levels is not
recommended to assess for toxicity or
efficacy
• If levels are requested, they are only
appropriate for mycophenolate mofetil
and should be drawn as a trough
• MPA AUC is a better predictor of clinical events than
MPA trough. Trough levels are poorly correlated with
AUC and are not recommended (UW Health, Very Low,
Conditional)
Adverse
effects
Diarrhea
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
o Consider colonoscopy if diarrhea persists and all
stool studies are negative
• If diarrhea work-up is negative for an infectious cause of diarrhea and it is affecting activities of daily
living or the patient is having limited and/or decreased oral intake:
o Decrease mycophenolate by 25% and increase dosing frequency (ex. 720 mg BID → 360 mg TID)
▪ If fails, decrease mycophenolate by 50%
o Follow up with patient in 1 week to assess continued symptoms and trend severity
o If dose is decreased to 180 mg twice daily (MYF) or 250 mg twice daily (MMF) consult provider
to determine if other immunosuppression needs to be adjusted
o Consider adding the following:
▪ Add loperamide (Imodium®) 2 mg as needed after each loose stool (max dose: 16 mg
daily)
▪ Diphenoxylate/atropine (Lomotil®) 5 mg four times daily as needed (max dose: 20
mg/day)
▪ Psyllium fiber (Metamucil®) 3.4 g daily as needed
Leukopenia • Consult transplant physician regarding further work up of leukopenia and to determine if
immunosuppression needs to be adjusted
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
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Contact: CCKM@uwhealth.org Last Revised: 07/2021
Heartburn/nausea • Counsel patient on taking MYF or MMF with food if not already doing so
• Convert from MMF to MYF if only upper GI complaints (heartburn, nausea)
• Add calcium carbonate as needed, or the addition of an H2RA or PPI if not already on
• If symptoms continue following one week of daily thearpy, increase H2RA or PPI dose to twice daily,
reassess in 1 week
• If symptoms persist for ≥1 week, consider EGD to rule out infection vs. ulceration
cGaston RS, Kaplan B, Shah T, et al. Fixed- or controlled-dose mycophenolate mofetil with standard or reduced-dose calcineurin inhibitors: the opticept trial. Am J Transplant. 2009;9(7):1607-19.
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
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Contact: CCKM@uwhealth.org Last Revised: 07/2021
Prednisone – pancreas transplant
Recommendations Notes/Evidence
Initiation Post-operative day 4 following dexamethasone taper • Prednisone 30 mg once daily will be started
on POD 4 following dexamethasone taper and
may be continued on discharge
Dosing
(initial)
Standard steroid taper
• Factors that may influence the
duration of prednisone taper:
o Current and historical CNI
levels
o Sensitization status
o Current MPA dose
o Episodes of rejection
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Discharge on 30 mg and after 2 week
follow up, decrease dose by 5 mg each
week to a target dose of 10 mg daily
• Steroid withdrawal can be considered for
patients who receive alemtuzumab for
induction (UW Health, Very Low, Conditional)
• Rapid steroid taper can be considered for
patients who receive alemtuzumab or
thymoglobulin for induction (UW Health, Very
Low, Conditional)
• Prednisone doses should be split to twice
daily dosing for patients requiring glucose
control (UW Health, Very Low, Conditional) Rapid steroid taper
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
20 mg POD5
10 mg POD6
Discharge on 10 mg daily and decrease
to 5 mg daily after 2 weeks if tacrolimus
is therapeutic
Early steroid withdrawal
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Steroid withdrawal on POD5
Labs Laboratory Monitoring: Glucose, bone mineral density
Adverse
effects
Hyperglycemia • Prednisone doses should be split to twice daily dosing for patients with hyperglycemia
Heartburn/reflux • Start proton pump inhibitor (PPI) at time of transplant. Should be continued for at least 3 months after transplant
• If a patient complains of heartburn on daily dosing of the PPI, frequency may be increased to twice daily (pending
renal function)
• Discontinue PPI in patients with no history of heartburn/gastroesophageal reflux disease (GERD) prior to
transplant if prednisone is discontinued
Osteoporosis • Recommend calcium 1200 mg daily (based on elemental calcium dosing)
• Recommend vitamin D 2000 units daily
• For patients that are on an early steroid withdrawal maintenance immunosuppression regimen, calcium and
vitamin D supplementation are not required
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Tacrolimus – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • Initiation of tacrolimus should start before or at
the time of transplant, rather than delayed until
the onset of graft function (UW Health, Very
Low, Conditional)
Dosing
(initial)
Decreased sensitivity (African-American, >80kg) 0.1 mg/kg/day (use ABW), by mouth divided in 2
doses twice daily, rounded to nearest capsule size
• Capsules and suspension may be taken with or
without food. Since the presence of food affects
the bioavailability of tacrolimus, if taken with
food, it should be taken consistently the same
way each time. (UW Health, Very Low,
Conditional)
• Tacrolimus may be given sublingually in patients
unable to adequately absorb enteral
formulations or in those unable to take oral. If a
patient is being transitioned to tacrolimus
sublingual from tacrolimus IR, each dose should
be divided by 2 and given sublingually. (UW
Health, Very Low, Conditional)
• Use of IV tacrolimus is reasonable for patients
unable to adequately absorb enteral
formulations, and conversion from IV to oral
tacrolimus is recommended as soon as enteral
therapy can be tolerated to minimize risk of
anaphylactic reactions that occur with
injectables containing castor oil derivatives.
(UW Health, Very Low, Conditional)
• Tacrolimus ER may be utilized in patients with
documented intolerable adverse effects with
tacrolimus IR or who are unable to obtain a
therapeutic drug concentration with the IR
formulation. If a patient is being transitioned to
tacrolimus ER (Envarsus®) from tacrolimus IR,
the total daily dose should be multiplied by 0.8,
then rounded to the nearest capsule size. (UW
Health, Very Low, Conditional)
Increased sensitivity (NPO, <80kg) Fixed dose 2 mg by mouth twice daily
Drug-drug
Interactions
(not an all-
inclusive
list)
Increases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Adjust tacrolimus dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor tacrolimus levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Monitor tacrolimus levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Concurrent use of mycophenolate +/- prednisone
Tacrolimus goals may differ if patient is not on
mycophenolate +/- prednisone regimen. Goal
level should be discussed with provider.
Target TAC Trough Level
DGF 7-9 ng/mL
0-3 months: 8-11 ng/mL
3-6 months: 7-9 ng/mL
6-12 months: 6-8 ng/mL
>12 months: 5-7 ng/mL
Below/Above
Target
>50% Adjust dose by 25-50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Laboratory Monitoring:
Tacrolimus (trough), potassium, and creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-90 Not less than weekly
91-180 Not less than twice
monthly
181-2 years Not less than once
monthly
>2 years Not less than quarterly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse
effects
Acute kidney injury • Assess tacrolimus trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease tacrolimus dose if trough is <4 ng/mL above goal
o Hold tacrolimus if trough >5 ng/mL above goal and consider increasing current prednisone
dose
Neurological symptoms (tremor, headache) • Assess tacrolimus trough level for correlation with tremors or headache
• If trough level is above goal, adjust tacrolimus dose and follow up with patient
• if trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to tacrolimus ER,
belatacept, cyclosporine, or refer to primary care provider for supportive therapy, such as
addition of low dose beta blocker (propranolol)
New onset diabetes after transplantation
(NODAT)
Diagnosis
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• No tacrolimus dose adjustment is recommended
• Consider consulting diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health
Organization (WHO) and American Diabetes Association (ADA) that develops for the first time after
transplantation
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent) and there have been 3 months of minimal glucocorticoid doses
o Consult transplant physician and consider converting the patient to cyclosporine
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Cyclosporine – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • The initiation of cyclosporine should start before
or at the time of transplantation, rather than
delayed until the onset of graft function (UW
Health, Very Low, Conditional)
Dosing
(initial)
Decreased sensitivity (African-American, >80kg) Fixed dose 150 mg by mouth twice daily • Neoral/Gengraf (cyclosporine modified) and
Sandimmune (cyclosporine non-modified) are not
bioequivalent and cannot be used
interchangeably (UW Health, Very Low,
Conditional)
• Capsules and suspension may be taken with or
without food. However, since the presence of
food affects the bioavailability of cyclosporine, if
taken with food, it should be taken consistently
the same way each time. (UW Health, Very Low,
Conditional)
Increased sensitivity (NPO, <80kg) Fixed dose 100 mg by mouth twice daily
Drug-Drug
Interactions
(not an all-
inclusive
list)
Increases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Adjust cyclosporine dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor cyclosporine levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Monitor cyclosporine levels and adjust as
needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Below/Above
Target
>50% Adjust dose 25% to 50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Goal CSA Level
0-3 months: 200-300 ng/mL
3-6 months: 150-250 ng/mL
6-12 months: 100-200 ng/mL
>12 months: 50-100 ng/mL
Laboratory Monitoring:
Cyclosporine (trough), potassium, and
creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-90 Not less than weekly
91-180 Not less than twice
monthly
181-2 years Not less than once
monthly
>2 years Not less than quarterly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse
effects
Acute kidney injury • Assess cyclosporine trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease cyclosporine dose if trough is <50 ng/mL above goal
o Hold cyclosporine if trough >50 ng/mL above goal and consider increasing current prednisone
dose
Neurological symptoms (tremor, headache) • Assess cyclosporine trough level for correlation with tremors or headache
• If trough level is above goal, adjust cyclosporine dose and follow up with patient
• if trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to tacrolimus ER,
belatacept, or refer to primary care provider for supportive therapy, such as addition of low
dose beta blocker (propranolol)
New onset diabetes after transplantation
(NODAT)
Diagnosis
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• No cyclosporine dose adjustment is recommended
• Consider consulting diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health Organization
(WHO) and American Diabetes Association (ADA) that develops for the first time after transplantation
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent) and there have been 3 months of minimal glucocorticoid doses:
o Consult transplant physician
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Belatacept – renal transplant
Recommendation Notes/Evidence
Dosing Induction dosing (starting post-transplant or
converting from CNI <6 months from transplant)
Day 0, day 4: 10 mg/kg/dose
Ends of weeks 2, 4, 8, 12: 10 mg/kg/dose
5 mg/kg/dose every 4 weeks (±3 days)
starting at week 16
• Indicated for use in patients who are EBV
seropositive as a replacement for CNIs or to allow for
CNI minimization (UW Health, Very Low, Conditional)
• EBV serostatus should be evaluated prior to
initiation of belatacept (UW Health, Very Low,
Strong)
Conversion dosing w/ CNI taper (converting from
CNI to belatacept >6 months from transplant)
Initial phase:
- Day 0: 5 mg/kg/dose
- End of weeks 2, 4, 6, and 8: 5 mg/kg/dose
Maintenance phase:
- 5 mg/kg/dose every 4 weeks (±3 days)
starting end of week 12
CNI taper:
- 100% of previous dose on days 1-14
- 50% of previous dose on days 15-28
- 25% of previous dose on days 29-41
- Discontinue CNI on day 42
Conversion dosing with no CNI taper (converting
from CNI to belatacept >6 months from
transplant)
Initial phase:
- Day 0: 10 mg/kg/dose
- End of weeks 2, 4, 6, and 8: 10 mg/kg/dose
Maintenance phase:
- 5 mg/kg/dose every 4 weeks (±3 days)
starting end of week 12
Labs Laboratory Monitoring:
Prior to initiation: EBV serostatus
Adverse
effects
Post-transplant lymphoproliferative disorder
(PTLD)
• Consult transplant provider if concerns for PTLD (weight loss, fatigue, unexplained
anemia/thrombocytopenia/leukopenia, hypercalcemia)
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Mycophenolate – renal transplant
Recommendation Notes/Evidence
Initiation Post-operative day 1 • Full dose mycophenolic acid is the preferred anti-
proliferative medication used for renal transplant
patients (UW Health, Very Low, Conditional)
• IV mycophenolate mofetil is indicated if the patient has
an acute condition that affects gastrointestinal
absorption (i.e., GI bleed or obstruction, malabsorption
syndromes, severe diarrhea or severe vomiting) (UW
Health, Very Low, Conditional)
• Mycophenolate mofetil suspension is utilized for
patients receiving medications via nasogastric or
orogastric tube
Dosing
(initial)
Mycophenolate sodium (Myfortic) 720 mg by mouth twice daily
Mycophenolate mofetil (Cellcept) 1000 mg by mouth twice daily
Drug-drug
interactions
(not an all-
inclusive
list)
Decreases mycophenolate concentration
*Check Lexicomp for dose adjustments*
• Cyclosporine
Target levels
Labs
Goal MPA Trough
CsA based
regimens:
1.3-2.8 mg/L
TAC based
regimens:
1.9-2.8 mg/L
Laboratory Monitoring:
• Lab monitoring of MPA levels is not
recommended to assess for toxicity or
efficacy
• If levels are requested, they are only
appropriate for mycophenolate mofetil
and should be drawn as a trough
• MPA AUC is a better predictor of clinical events than
MPA trough. Trough levels are poorly correlated with
AUC and are not recommended (UW Health, Very Low,
Conditional)
Adverse
effects
Diarrhea
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
o Consider colonoscopy if diarrhea persists and
all stool studies are negative
• If diarrhea work-up is negative for an infectious cause of diarrhea and it is affecting activities of daily
living or the patient is having limited and/or decreased oral intake:
o Decrease mycophenolate by 25% and increase dosing frequency (ex. 720 mg BID → 360 mg
TID)
▪ If fails, decrease mycophenolate by 50%
o Follow up with patient in 1 week
o If dose is decreased to 180 mg twice daily (MYF) or 250 mg twice daily (MMF) consult provider
to determine if other immunosuppression needs to be adjusted
o Consider adding the following:
▪ Add loperamide (Imodium®) 2 mg as needed after each loose stool (max dose: 16 mg
daily)
▪ Diphenoxylate/atropine (Lomotil®) 5 mg four times daily as needed (max dose: 20
mg/day)
▪ Psyllium fiber (Metamucil®) 3.4 g daily as needed
Heartburn/nausea • Counsel patient on taking MYF or MMF with food if not already doing so
• Convert from MMF to MYF if only upper GI complaints (heartburn, nausea)
• Add calcium carbonate as needed, or the addition of an H2RA or PPI if not already on
• If symptoms continue following 1 week of daily therapy increase H2RA or PPI dose to twice daily,
reassess in 1 week
• If symptoms persist for ≥1 week, consider EGD to rule out infection vs. ulceration
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Azathioprine – renal transplant
Recommendation Notes/Evidence
Initiation Failure to tolerate mycophenolate
Dosing
(initial)
1-2 mg/kg by mouth daily • Azathioprine is recommended for use in patients
unable to tolerate adverse effects of mycophenolate
(UW Health, Very Low, Conditional)
• Azathioprine is considered to be less effective than
MPA in preventing rejection. Prior to initiating
azathioprine, consider the total immunosuppression
for the patient and timing out from transplant
Drug-drug
interactions
(not an all-
inclusive
list)
Increases azathioprine concentration:
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Febuxostat
Adjust azathioprine dose empirically:
• Allopurinol
Labs Laboratory Monitoring:
• There is no recommended azathioprine level for monitoring purposes. However, if toxicity is
suspected, check thiopurine methyltransferase (TPMT)
Adverse
effects
Leukopenia • Consult transplant provider if WBC <3
Gastrointestinal
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
Consider colonoscopy if diarrhea persists and all stool
studies are negative
• See diarrhea work-up algorithm
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Sirolimus/everolimus – renal transplant
Recommendations Notes/Evidence
Initiation For use in patients with:
• CNI toxicity
• Skin cancer
Quadruple therapy
• Sirolimus/everolimus may impair or delay wound healing,
and should be used with caution in the peri-surgical
period (UW Health, Very Low, Conditional)
• Indicated for use in patients with recurrent skin cancers
as a replacement for azathioprine, MPA, or CNIs (UW
Health, Very Low, Conditional)
Dosing (initial) Sirolimus 6 mg load on day 1, followed by 2 mg by
mouth once daily
Everolimus 0.75 mg by mouth twice daily
Drug-drug
interactions (not
an all-inclusive
list)
Increase mTOR concentration (not an all-
inclusive list):
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Posaconazole
• Voriconazole
• Ritonavir
Monitor mTOR levels and adjust as needed:
• Fluconazole
• Ritonavir
• Letermovir
• Clarithromycin
• Erythromycin
Decrease mTOR concentration (not an all-
inclusive list)
*Check Lexicomp for dose adjustments*
Monitor mTOR levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Laboratory Monitoring:
• Recommended once weekly upon initiation and with any dose changes
• When the target trough level has been attained, recommend monitoring levels once
monthly
Goal Trough Levels
(SIRO/EVR+TAC)
Goal Sirolimus Level
(SIRO/EVR+MPA)
0-3 months: TAC: 5-7 ng/mL
SIRO/EVR: 4-7 ng/mL
SIRO/EVR: 8-10 ng/mL
3-6 months: TAC: 5-7 ng/mL
SIRO/EVR: 4-7 ng/mL
SIRO/EVR: 8-10 ng/mL
6-12 months: TAC: 3-5 ng/mL
SIRO/EVR: 3-5 ng/mL
SIRO/EVR: 5-8 ng/mL
>12 months: TAC: 3-5 ng/mL
SIRO/EVR: 3-5 ng/mL
SIRO/EVR: 5-8 ng/mL
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse effects Proteinuria • Monitor at 6 months and then annually post-transplant per standard lab monitoring
• Consider administration of angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II receptor
antagonists and reducing mTOR levels
Mouth ulcers • Development of mouth ulcers also seems to be dose-related, because they usually appear after the
loading dose and often improve after a dose reduction
• Addition of a high-potency topical steroid may be considered
Hyperlipidemia • Monitor cholesterol and lipids
• If hyperlipidemia occurs, follow current guidelines for management (diet, exercise, lipid lowering agents)
• Immunosuppressive strategies minimizing doses of mTORs, CNIs, or corticosteroids may help in
controlling hyperlipidemia
Thrombocytopenia • Consider dose reduction or temporary drug suspension if appropriate
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Prednisone – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 4 following dexamethasone taper • Prednisone 30 mg once daily will be
started on POD 4 following
dexamethasone taper and may be
continued on discharge
Dosing
(initial)
Standard steroid taper
• Prednisone taper should occur
following POD4
• Factors that may influence the
duration of prednisone taper:
o Current and historical CNI levels
o Current MPA dose
o Current renal function
o Episodes of rejection
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Discharge on 30 mg and decrease dose by 5
mg each week to a target dose of 10 mg daily
• Steroid withdrawal can be considered
for patients who receive alemtuzumab
for induction (UW Health, Very Low,
Conditional)
• Rapid steroid taper can be considered
for patients who receive alemtuzumab
or thymoglobulin for induction (UW
Health, Very Low, Conditional)
• Prednisone doses should be split to
twice daily dosing for patients requiring
insulin for glucose control (UW Health,
Very Low, Conditional)
Rapid steroid taper
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
10 mg POD5
Discharge on 10 mg and consider reduction to
5 mg at week 3 to target dose of 5 mg daily
Early steroid withdrawal
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Steroid withdrawal on POD5
Labs Laboratory Monitoring:
Glucose, bone mineral density
Adverse
effects
Hyperglycemia • Prednisone doses should be split to twice daily dosing for patients requiring insulin for glucose control
Heartburn/reflux • Start a proton pump inhibitor (PPI) at time of transplant
• If a patient complains of heartburn on daily dosing of the PPI, frequency may be increased to twice daily
(pending renal function)
• Discontinue PPI in patients with no history of heartburn/gastroesophageal reflux disease (GERD) prior to
transplant if prednisone is discontinued
Osteoporosis • Recommend calcium 2000 mg daily (based on elemental calcium dosing)
• Recommend vitamin D 2000 units daily
• For patients that are on an early steroid withdrawal maintenance immunosuppression regimen, calcium and
vitamin D supplementation are not required
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
UW Health Kidney Transplant Induction and Desensitization Protocols
Donor
Status
Protocol Virtual XM Sum MFI
PE + IVIG (100mg/kg
after each PE);
MPA / TAC Desensitization
Induction Regimen Prednisone
Taper
Live
D0 Negative -
-
ESW: Alemtuzumab 30mg x1
OR
Thymoglobulin 1.5mg/kg daily x3-4
• Discontinue POD5
- Non-ESW: Basiliximab 20mg x1
• Discharge on 10mg/day1
• Consider reduction to 5mg at week 3
• Target dose 5mg/day
D1
Weak
positive <1000 MPA/TAC:d(-7) • Discharge on 30mg/day
• Reduce daily dose by 5mg each week
• Target dose 10mg/day
D2 Positive
1,000 -
4,000
1,000 -
4,000
PE/IVIG: 2-3 pre-Tx and
post-Tx;
MPA/TAC:d(-7)
Deceased
D5a Negative -
-
ESW: Alemtuzumab 30mg x1
OR
Thymoglobulin 1.5mg/kg daily x3-4 • Discontinue POD5
- Non-ESW: Basiliximab 20mg x1
-
D5b
Weak
positive <1000 -
D5c Positive
PE/IVIG: Pre-Tx: 1
Post-Tx: 2-3 Thymoglobulin 1.5mg/kg daily x 4
1 - Rapid Steroid Taper: Dex 100mg IVx1, Dex 50mg IVx1, Pred 90mg POx1, Pred 60mg POx1, Pred 30 mg POx1, Pred 10 mg PO daily
Post-reperfusion biopsy recommended for all patients • Patients with GN should receive Thymoglobulin and steroid continuation
Patients receiving an A2 to B Transplant with anti-A titer ≥1:16 receive Thymoglobulin ≤1:8 receive 2 doses of Basiliximab
Thymoglobulin 1.5mg/kg daily x 4
OR
Thymoglobulin 1.5mg/kg daily x3-4
• Discharge on 10mg/day1
• Consider reduction to 5 mg at week 3
• Target dose 5mg/day
• Discharge on 30mg/day
• Reduce daily dose by 5mg each week
• Target dose 10mg/day
Alemtuzumab 30mg x1
OR
Thymoglobulin 1.5mg/kg daily x3-4
Non-ESW + High DGF Risk:
Alemtuzumab 30mg x1
OR
Thymoglobulin 1.5mg/kg daily x3-4
Alemtuzumab 30mg x1
OR
Thymoglobulin 1.5mg/kg daily x3-4
07/2021
Rejection Protocols
R1 Inpatient: Dex 50mg IV x 1, Dex 44mg IV x 1 (omit for outpatients), then prednisone taper2; Outpatient: Dex 50mg IV x 1, then prednisone taper2
R2 Dex 100mg IV x1, Dex 50mg IV x1, Dex 44mg IV x1 (omit for outpatients), followed by prednisone taper2
R3 R2 + Thymo (1.5mg/kg daily x 4-7)
R4a Early ABMR4: R2 + PE/IVIG (100mg/kg) x 4-6 then IVIG (500 mg/kg/week) x4 ± Ritux3 375 mg/m2 x1
R4b Late ABMR4: R2 + IVIG (500mg/kg/week) x 4 ± Ritux3 375 mg/m2 x 1
R5 R2 + PE/IVIG (early only4) x 4-6 + Thymo (1.5mg/kg daily x 5-7) + IVIG (500 mg/kg/week) x 4 ± Ritux3 375 mg/m2 x1
2 Standard Prednisone Taper: 180mg x1, 150mg x1, 120mg x1, 90mg x1, 60mg x1, 30mg daily x 7 days, then 20mg daily x 7 days,
then 10 mg daily until clinic appointment. Dexamethasone dosed daily, prednisone total daily dose split BID
3 Ritux use not recommended if ABMR injury is minimal (focal C4d, without microcirculation inflammation); following PE if concurrent
4 Early is defined as 0-6 months following transplant, late is > 6 months following transplant
All weight-based medication dosing should use IBW unless other weight is specified
Abbreviations
A2B=ABO B recipient of an A donor; ABMR=Antibody mediated rejection; CMV=Cytomegalovirus, d=Day; Dex=Dexamethasone IV; DGF=Delayed Graft Function; DSA=Donor Specific Antibody; ESW=Early Steroid Withdrawal;
GN=Glomerulonephritis; IBW=Ideal Body Weight; IVIG=Intravenous Immune Globulin; MFI=Mean Fluorescent Intensity; MPA=Mycophenolic Acid; PE=Plasma Exchange; POD=Post-Op Day;
PJP=Pneumocystis Jiroveci Pneumonia; PUD=Peptic Ulcer Disease; Ritux=Rituximab; TAC=Tacrolimus; TCMR=T-cell Mediated Rejection; Thymo=Thymoglobulin; XM=Cross match
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Disclaimer: This Clinical Practice Guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a
protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish
the only appropriate approach to a problem.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority, University of Wisconsin Medical Foundation, Inc, UW-Madison
UW Health Kidney Rejection Treatment Protocols
TCMR
IA IB IIA IIB III
Type
Banff
Protocol #
Suspicious
R1 R2 R3
Start CMV, thrush, PJP, PUD prophylaxis
Follow-up biopsy recommended at 12 weeks (± 1 week) for all patients
DSA Monitoring: Monthly x 3 months, 6 months, 12 months, annually
Mixed
-
R5
ABMR
Banff 2019
R4
Aji Djamali, MD - Nephrology
(608) 262-7330 • axd@medicine.wisc.edu
Didier Mandelbrot, MD - Nephrology
(608) 262-4352 • damandel@medicine.wisc.edu
David Hager, PharmD – Pharmacy
(608) 890-8993 • dhager@uwhealth.org
07/2021
Abdominal Transplant Immunosuppression Mananagement Adult Inpt Amb 210617
Appendix A - Liver Transplant 210617
Appendix B - Pancreas Transplant 210617
Appendix C - Renal Transplant 210617
Appendix D - Kidney Transplant Induction 210617