Beth Israel Deaconess Medical Center
Transplant Manual
Title: Sirolimus Conversion - Calcineurin Inhibitor Withdrawal Protocol
Purpose: To provide a rational approach to sirolimus conversion for liver
transplant patients
Policy statement:
1. The use of calcineurin inhibitor-based immunosuppression has led to an
increased incidence of renal failure in liver transplant recipients, with 50-80% of
patients developing renal dysfunction at some time post-transplant and up to
15% of patients progressing on to ESRD at 5 years.
2. Renal transplant recipients receiving a sirolimus-based immunosuppression
protocol have demonstrated a more consistent improvement in renal function
post-op compared to calcineurin inhibitor-based protocols.
3. Conversion from a calcineurin inhibitor-based protocol to a sirolimus-based
protocol has been shown to result in improvement in renal function in both
renal and liver transplant recipients.
4. Sirolimus has been shown to inhibit growth of human hepatoma cells in vitro; in
contrast, tacrolimus has been shown to accelerate hepatoma cell growth.
5. Sirolimus may have beneficial effects on tumor recurrence in liver transplant
recipients who have a history of hepatoma.
Recommendations for evaluation and conversion to sirolimus
The following conditions should exist for patient to be eligible for conversion:
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Patients with evidence of calcineurin inhibitor nephrotoxicity defined as an
increase in an SCR of >30% from baseline or a GFR of less than 55 ml/min but
greater than 40 ml/min;
Patients transplanted for a primary diagnosis of hepatocellular cancer (HCC) or
an incidental finding of HCC in the explanted liver;
Patient must be a minimum of 6 weeks post liver transplantation;
No evidence of thrombosis or of clinically significant stenosis of hepatic artery,
hepatic vein, or portal vein as documented on ultrasound within 4 weeks prior
to conversion;
All surgical wounds must be fully healed;
Total white blood cell count >3,000/mm3, platelet count >75,000/mm3, fasting
triglycerides <350 mg/dL, fasting cholesterol <300 mg/dL.
Patients should not be converted if they have had a recent rejection episode (within
the previous 4 weeks), if they have any evidence of systemic infection (i.e., sepsis,
bacteremia, pneumonia, etc.), or if they have a history at any time of hepatic artery
thrombosis, portal vein thrombosis, or a hypercoagulable state.
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Conversion protocol for patients < 6 months post-transplant:
Day 1:
Decrease calcineurin inhibitor dose to ½ of current dose and continue
for a minimum of 3 days post conversion or until a sirolimus trough of 6
ng/mL has been achieved. If patient is still on fluconazole prophylaxis,
start sirolimus at 2 mg daily. If patient is not on fluconazole prophylaxis,
start at 4 mg daily.
Day 5:
Check a sirolimus trough.
Time post conversion
0-3 months
3-6 months
6-12 months
Target trough
8-10 ng/mL
6-8 ng/mL
6 ng/mL
Conversion protocol for patients > 6 months post transplant:
Day 1:
Discontinue calcineurin inhibitor on the evening prior to conversion. Start
sirolimus at 4 mg daily and check a trough 5 days post conversion.
Target above trough levels.
Following conversion patients must have their dose adjusted to obtain a target trough
of 6-10 ng/mL. If the trough level is outside the target range, the formula below can
be used to calculate the new maintenance dose. Check a trough 5-7 days after dose
change.
NEW DOSE =
(mg)
CURRENT
DOSE
(mg)
as currently
given
X
DESIRED TROUGH
LEVEL
CURRENT TROUGH
LEVEL
(ng/mL)
Additional monitoring parameters:
1. Sirolimus trough on day 5 after initiation of therapy or after change of sirolimus
dose. Biweekly sirolimus troughs for the first 4 weeks after conversion or
dosage change. Once stable, sirolimus trough levels may be drawn on a
weekly, biweekly or monthly basis
2. Fasting lipid panel at baseline prior to conversion and q 4 months until 12
months post conversion, then q 6 months
3. Liver function tests, CBC, renal panel biweekly for 2 weeks, weekly for 1
month; then resume regular lab schedule
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Vice President Sponsor:
Approved by:
x Liver Selection Committee
Requestor Name:
Original Date Approved:
Next Review Date:
Revised:
Dianne Anderson, Sr. VP PCS
Douglas W. Hanto, MD, PhD and Michael Curry, MD
Co-Chairs
Michael Curry, MD
2/05
1/08
12/06
Eliminated:
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