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Non-Thoracic Solid Organ Transplant Antiviral Prophylaxis – Adult – Inpatient [17]

Non-Thoracic Solid Organ Transplant Antiviral Prophylaxis – Adult – Inpatient [17] - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Delegation/Practice Protocols, Inpatient Delegation Protocols


Delegation Protocol Number: 17
Delegation Protocol Title:
Non‐Thoracic Solid Organ Transplant Antiviral Prophylaxis - Adult ‐ Inpatient
Delegation Protocol Applies To:
UW Health adult inpatients on the (kidney, liver, medical or pancreas) transplant service who have received a
kidney, liver or pancreas transplant or any combination thereof, and who do not have clinical or laboratory
evidence of or diagnosis of active CMV disease.
Target Patient Population:
Any adult patients who have received non‐thoracic solid organ transplant (a kidney, liver, pancreas transplant or
any combination thereof) or who are actively undergoing treatment for rejection of a non-thoracic solid organ
transplant.
Delegation Protocol Champions:
Arjang Djamali, MD, Department of Medicine – Nephrology
John Rice, MD, Department of Medicine – Gastroenterology
Delegation Protocol Reviewer:
David Hager, PharmD, Pharmacy – Inpatient Services
Responsible Department:
Department of Pharmacy
Purpose Statement:
To delegate authority from the attending physician to clinical pharmacists to determine and order the
appropriate antiviral prophylaxis for solid organ transplant patients (kidney, liver, pancreas or any combination
thereof) postoperatively and based on their rejection treatment regimen.
Who May Carry Out This Delegation Protocol:
Inpatient clinical pharmacists trained in the use of this delegation protocol.
Guidelines for Implementation:
1. The clinical pharmacist identifies a patient with a non‐thoracic solid organ transplant during the current
hospitalization or a patient actively treated for rejection of a non‐thoracic solid organ transplant. The
induction or rejection agent used in treatment is identified through the Health Link medication record.
2. For new kidney, liver, pancreas, or any combination of these transplants the clinical pharmacist determines
the appropriate anti‐viral regimen based on the recipient CMV status documented Health Link, the donor
CMV status, and induction agent. The organ donor CMV status is obtained from the University of Wisconsin
Organ and Tissue Donation via the patient unit specific fax machine.
3. The pharmacist orders appropriate antiviral therapy per protocol after surgery according to Table 1 using
the doses listed in Tables 2 and 3 and the patient’s most recent creatinine clearance estimate.
4. In patients who receive a liver transplant alone or in combination with any other abdominal organ and is to
receive valganciclovir based on Table 1, the pharmacist orders IV ganciclovir based on the doses listed in
Table 4 and the patient’s most recent creatinine clearance estimate. When the patient transfers to the floor,
the clinical pharmacist discontinues IV ganciclovir and initiates the appropriate PO valganciclovir therapy
based on Table 1, Table 2, and the patient’s most recent creatinine clearance estimate.
5. If a patient is admitted to the medical, kidney, liver or pancreas transplant service and is treated for
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 11/2017CCKM@uwhealth.org


rejection, defined as at least one dose of intravenous dexamethasone 20 mg or greater, lymphocyte
depleting agents (alemtuzumab, antithymocyte globulin) or agents for the treatment of antibody-
mediated rejection (bortezomib, eculizumab, rituximab) , then the clinical pharmacist initiates the
appropriate antiviral therapy:
5.1. If the patient is CMV seropositive (R+) valganciclovir will be initiated at the prophylactic dose
listed in Table 2 for 1 month if treated with steroids alone and no historical CMV infection,
otherwise total duration of 3 months.
5.2. If the patient is CMV seronegative (R-) repeat CMV IGG will be sent to determine presence of
seroconversion.
a If repeat IGG negative and the historical donor was CMV seronegative (D-); acyclovir
will be initiated for 1 month at the prophylactic dose listed in Table 3.
b If repeat IGG negative and the historical donor was CMV seropositive (D+);
valganciclovir will be initiated as per 5.1.
c If repeat IGG positive; valganciclovir will be initiated as per 5.1.
5.3. If the patient is already on valganciclovir prophylaxis as an outpatient, it will be continued for an
additional 1 or 3 months (in accordance to 5.1) from the time treatment for rejection occurred.
6. The clinical pharmacist enters orders to discontinue anti‐viral prophylactic therapy not in agreement with
this protocol and enters the appropriate antiviral therapy in Health Link.
7. The pharmacist enters a note in the electronic medical record indicating antiviral prophylaxis therapy has
been ordered per protocol. For a new transplant patient, the clinical pharmacist will document the induction
agent used, recipient CMV immune status, donor CMV immune status, UNOS ID number of the donor, and
anti-viral regimen selected. For a patient being treated for rejection, the clinical pharmacist will document
the rejection agent, additional information about donor CMV immune status if necessary (see 5.0), and anti‐
viral regimen selected.
8. This protocol may be overridden at any time by an order for anti‐viral prophylaxis that indicates “antiviral
prophylaxis–dispense as written” or similar designation in the administration instructions of the order.

Table 1. Antiviral agent for antiviral prophylaxis based on induction agent
Agent for Induction
Recipient & Donor CMV
Status
Antiviral Agent
Antithymocyte rabbit
thymoglobulin (ATG)
If either status if positive Valganciclovir for 6 months
If both are negative Acyclovir for 3 months
Alemtuzumab
(Campath®)
If either status if positive Valganciclovir for 6 months
If both are negative Acyclovir for 3 months

Basiliximab
(Simulect®)
Or
No Induction
Recipient negative; donor
positive (D+/R-) Valganciclovir for 6 months
Recipient positive (R+) Valganciclovir for 3 months (6 months for pancreas)
If both are negative (D-/R-) Acyclovir for 3 months
*Valganciclovir dosing per Table 2
**Acyclovir dosing per Table 3






Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


Table 2. Valganciclovir Dosing for Antiviral Prophylaxis
Creatinine Clearance Oral Valganciclovir Dose
> 60 mL/min 900 mg daily
40‐59 mL/min 450 mg daily
25‐39 mL/min 450 mg every other day
< 25 mL/min 450 mg twice weekly

*Under-dosed (val)ganciclovir is a risk-factor for ganciclovir resistant CMV or non-responsiveness to therapy. Dose
reduce for renal function conservatively; select the higher dose for borderline or improving creatinine clearance.






**Switch patients who develop leukopenia (ANC < 500/mm3) on valganciclovir to pre-emptive monitoring. Dose
reduction is a risk factor for ganciclovir resistance and should not be done.

Table 3. Acyclovir Dosing for Antiviral Prophylaxis
Creatinine Clearance Oral Acyclovir Dose
> 10 mL/min/1.73m2 e400 mg twice daily
< 10 mL/min/1.73m2 200 mg twice daily

Table 4. Ganciclovir IV Dosing for Antiviral Prophylaxis
Creatinine Clearance IV Ganciclovir Dose**
> 70 mL/min 5 mg/kg every 24 hr
50‐69 mL/min 2.5 mg/kg every 24 hr
25‐49 mL/min 1.25 mg/kg every 24 hr
10‐24 mL/min 0.625 mg/kg every 24 hr
< 10 mL/min 0. 625 mg/kg 3 times/week after
hemodialysis
Dose based on ideal body weight (IBW). If 130% above IBW, use adjusted body weight, or if ABW < IBW then
use ABW
Order Mode: Protocol/Policy, Without Cosign

References:
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suppression of cytomegalovirus disease after renal transplantation. Clin Pharmaco Ther. Aug
1988;44(2):158‐163.
2. Martin M, Mañez R, Linden P, et al. A prospective randomized trial comparing sequential ganciclovir‐high
dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant
recipients. Transplantation. Oct 1994;58(7):779‐785.
3. Cytomegalovirus. Am J Transplant. Nov 2004;4 Suppl 10:51‐58.
4. Razonable R. Cytomegalovirus infection after liver transplantation: current concepts and challenges. World J
Gastroenterol. Aug 2008;14(31):4849‐4860.
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liver transplant recipients. Antimicrob Agents Chemother. Oct 2000;44(10):2811‐2815.
6. Cochrane A. Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant
recipients. Am J Health Syst Pharm. Oct 2006;63(19 Suppl 5):S17‐21.
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ganciclovir or valganciclovir prophylaxis. Am J Transplant. Jun 2003;3(6):731‐735.
8. Keven K, Basu A, Tan H, et al. Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney
and pancreas‐kidney transplantation under antibody preconditioning. Transplant Proc. Dec
2004;36(10):3107‐3112.
9. Paya C, Humar A, Dominguez E, et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention
of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. Apr 2004;4(4):611‐620.
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org


10. Weng F, Patel A, Wanchoo R, et al. Oral ganciclovir versus low‐dose valganciclovir for prevention of
cytomegalovirus disease in recipients of kidney and pancreas transplants. Transplantation. Feb
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11. Kletzmayr J, Kotzmann H, Popow‐Kraupp T, Kovarik J, Klauser R. Impact of high‐dose oral acyclovir
prophylaxis on cytomegalovirus (CMV) disease in CMV high‐risk renal transplant recipients. J Am Soc
Nephrol. Feb 1996;7(2):325‐330.
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ganciclovir for cytomegalovirus prophylaxis in high‐risk kidney transplant recipients. Transplantation. Dec
1998;66(12):1682‐1688.
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patients: an evidence‐based reassessment of safety and efficacy. PLoS One. 2009;4(5):e5512.
14. Fletcher C, Englund J, Edelman C, Gross C, Dunn D, Balfour HJ. Pharmacologic basis for high dose oral
acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients. Antimicrob Agents Chemother.
May 1991;35(5):938‐943.
15. Bertoni E, Rosati A, Zanazzi M, et al. Cytomegalovirus disease prophylaxis in renal transplantation by high
dose oral acyclovir: efficacy and limits. Transplant Proc. Aug 1998;30(5):2094.
16. Rubin R, Kemmerly S, Conti D, et al. Prevention of primary cytomegalovirus disease in organ transplant
recipients with oral ganciclovir or oral acyclovir prophylaxis. Transpl Infect Dis. Sep 2000;2(3):112‐117.
17. Winston D, Busuttil R. Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction
with intravenous ganciclovir for long‐term prophylaxis of cytomegalovirus disease in cytomegalovirus‐
seropositive liver transplant recipients. Transplantation. Jan 2003;75(2):229‐233.
18. Winston D, Wirin D, Shaked A, Busuttil R. Randomised comparison of ganciclovir and high‐dose acyclovir for
long‐term cytomegalovirus prophylaxis in liver‐transplant recipients. Lancet. Jul 1995;346(8967):69‐74.
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UWHC Internal Document References:
1. UW Health Renal Function-Based Dose Adjustment Adult – Inpatient/Ambulatory [8] Delegation Protocol.
Accessed March 20, 2017.

Approved By:
UWHC Antimicrobial Use Subcommittee: May 2012; *March 2015; *March 2017
UWHC Pharmacy & Therapeutics Committee: May 2012; *March 2015; *April 2017
UWHC Medical Board: June 2012; *March 2015; *April 2017

Effective Date: April 2017

Scheduled for Review: April 2020
*Expedited Review Process












Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised:
 
11/2017CCKM@uwhealth.org