Related | Appendix B: Pancreas Transplant
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.
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 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.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
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.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
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.