Download Guideline for CMV Prophylaxis and Treatment in Lung Transplant

Guideline for CMV Prophylaxis and Treatment in Lung Transplant
Recipients
Indications: Post-Lung Transplant Patients
Procedure: The lung is a major site for Cytomegalovirus (CMV) latency and recurrence. All donors
and transplant candidates will be screened for CMV status prior to transplant. The transplant provider
will order appropriate medication and monitoring parameters.
Pre-Transplant Serologic Status and Risk for CMV Disease
High Risk
Donor (+) / Recipient (-)
Intermediate Risk
Donor (+) / Recipient (+)
Donor (-) / Recipient (+)
Low Risk
Donor (-) / Recipient (-)
I. CMV Prophylaxis
A. Initiated for all high and intermediate risk lung transplant recipients
Ganciclovir 5 mg/kg IV BID
^^^
Induction
High Risk
Intermediate
Risk
###
Low Risk
Cytomegalovirus Immune Globulin (Cytogam®)
• Within 72 hours: 150 mg/kg
• Weeks 2, 4, 6, 8: 100 mg/kg
• Weeks 12, 16:
50 mg/kg
Maintenance***
Valganciclovir (Valcyte®) 900 mg PO BID x 14 days
followed by
®
Valganciclovir (Valcyte ) 900 mg PO Daily x 12 months
Induction^^^
Ganciclovir 5 mg/kg IV BID
Maintenance***
Valganciclovir (Valcyte®) 900 mg PO BID x 14 days
followed by
®
Valganciclovir (Valcyte ) 900 mg PO Daily x 12 months
Induction
None
Maintenance&&
Acyclovir 400 mg Oral BID x 12 months
&
^^^ Administer ganciclovir IV therapy until patient no longer NPO and able to tolerate PO meds. If renally
impaired, dose ganciclovir appropriately
*** Begin valgancilovir once patient can swallow pills/suspension. If renally impaired, dose valganciclovir
appropriately
### Ensure leuko-depleted/CMV(-) blood products for recipient
&&& For prevention of HSV and VZV reactivation ONLY; does not cover CMV
B. If unable to acquire or tolerate valganciclovir (i.e. adverse effects, costs, insurance, etc.),
consider the following options:
1. Preemptive therapy in addition to the following:
a. Acyclovir 400 mg PO BID x 6-12 months OR
b. Valacyclovir 2 grams PO QID x 6-12 months
2. If valganciclovir is discontinued due to leucopenia, then check CMV
antigenemia weekly. If patients ANC < 1000, check CMV PCR instead.
II. CMV Treatment
A. Initiate treatment if CMV Rapid Antigen (pp65 antigenemia) is positive. Acquire CMV
DNA by PCR (quantitative) as soon as possible and continue to treat for asymptomatic or
symptomatic patients.
B. Asymptomatic patient
CMV Viral Load
(DNA PCR)
Treatment ***
Secondary Prophylaxis
^^^
Monitoring
< 1000 copies/mL
> 1000 copies/mL
None
Ganciclovir 5 mg/kg IV Q 12 Hours
or
Valganciclovir 900 mg PO BID
None
Valganciclovir 900 mg PO Daily ###
• CMV PCR weekly until 3 consecutive (-)
results
• CMV PCR weekly until negative
• CBC and BMP weekly in
treatment phase
*** Duration: minimum of 14 days based on clinical symptoms and virologic clearance (two consecutive negative
samples). Initial treatment with IV ganciclovir recommended for severe or life- threatening disease, high viral
load, or questionable GI absorption
^^^ Duration: 1-3 months, beginning 1 week after negative CMV PCR
### If recurrence of PCR > 1000 within 3 months of previous treatment, then continue valganciclovir 900 mg PO
Daily for life
C. Symptomatic patient and/or Tissue-Invasive Disease
CMV Viral Load
(DNA PCR)
> 250 copies/mL
Ganciclovir 5 mg/kg IV Q 12 Hours
Treatment ***
Secondary
Prophylaxis ^^^
Monitoring
D (+) / R (-) Cytogam® IV (100
mg/kg)###
Valganciclovir 900 mg PO Daily
• CMV PCR every 72 hours until negative
• CBC and BMP weekly while in treatment
phase
*** Duration: minimum of 14 days based on clinical symptoms and virologic clearance
^^^ Duration: 1-3 months, beginning when clinical symptoms improve
### Days 1, 4, and 7. For critically ill patients, administer additional doses on Days 14
and 21.
D. Ganciclovir Resistance (2 weeks of treatment with increasing/unchanged viral load)
1. Send for CMV genotypic resistance testing (mutations in UL97 and UL54)
2. Consult Infectious Disease service
3. Empiric Treatment:
Severe CMV Disease ***
Non-Severe CMV Disease
Ganciclovir 5 mg/kg IV Q 12 Hours
Ganciclovir 10 mg/kg IV Q 12 Hours
or
add / switch to
^^^
Foscarnet 60 mg/kg IV Q 8 Hours
Foscarnet 60 mg/kg IV Q 8 Hours
Valganciclovir 900 mg PO Daily x 1-3
Valganciclovir 900 mg PO Daily x 1-3
Secondary
months
months
Prophylaxis
• CMV PCR weekly until negative
• CMV PCR weekly until negative
Monitoring • CBC and BMP weekly while in
• CBC and BMP weekly while in
treatment phase
treatment phase
*** Consider dose reduction of immunosuppressive therapy in patients with severe CMV disease, nonresponsive
disease, high viral loads, and/or leucopenia. Consider Cytogam® as an adjunct to
antiviral therapy.
^^^ Continue therapy until symptoms improve, then start secondary prophylaxis. Adjust dosing of
medications
based upon renal function.
Treatment
4. Definitive Treatment
a. Guided by results of genotypic testing
References:
1. Zamora MR, Davis RD, Colm L. Management of cytomegalovirus infection in lung
transplant recipients: evidence-based recommendations. Transplantation. 2005;80:157-63.
2. Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the
management of cytomegalovirus in solid organ transplanatation. Transplanation. 2011;
89:779-95.
3. Razonable RR. Humar A, et al. Cytomegalovirus in solid organ transplantation. American
Journal of Transplantation. 2013; 13:93-106.
4. Snydman DR, Limaye AP, Potena L, et al. Update and review: state-of-the-art management
of cytomegalovirus infection and disease following thoracic organ transplantation.
Transplantations Proceedings. 2011; 43:S1-17.
5. Mitsani D, Nguyen MH, Kwak EJ, et al. Cytomegalovirus disease among donor-posititve /
recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis. Journal
of Heart Lung Transplant. 2010; 29:1014-20.
6. Copeland AF, Davis WA, Snyder LD, et al. Long term efficacy and safety of 12-months of
valganciclovir prophylaxis compared with 3 months after lung transplantation: a singlecenter, long-term, follow-up analysis from a randomized, controlled cytomegalovirus
prevention trial. 2011; 30:990-6.
7. Bonaros N, Mayer B, Schachner T, et al. CMV-hyperimmune globulin for preventing
cytomegalovirus infection and disease in solid organ transplant recipients: a meta-analysis.
Clin Transplant. 2008; 22:89-97.
8. Kruger RM, Paranjothi S, Storch GA, et al. Impact of prophylaxis with cytogam alone on the
incidence of CMV viremia in CMV-seropositive lung transplant recipients. Journal of Heart
Lung Transplant. 2003; 22:754.
9. Zamora MR, Nicolls MR, Hodge TN, et al. Following universal prophylaxis with
intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and
effective for prevention of CMV infection following lung transplantation. American Journal
of Transplantation. 2004; 4:1635-42.
10. Asberg A, Humar A, Rollag H, et al. Oral valganciclovir is noninferior to intravenous
ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients.
American Journal of Transplant. 2007; 2106-13.
Dosing of Antiviral Mediations for Renal Impairment
Ganciclovir (Cytovene®) - IV
Creatinine
Clearance
(mL/min)
≥ 70
Induction Dose
(mg/kg/dose)
Dosing Interval
(hours)
Maintenance Dose
(mg/kg/dose)
Dosing Interval
(hours)
5
12
5
24
50 to 69
2.5
12
2.5
24
25 to 49
2.5
24
1.25
24
10 to 24
1.25
0.625
< 10
1.25
24
3 times weekly
post-HD
24
3 times weekly
post-HD
0.625
Valganciclovir (Valcyte®)
Creatinine Clearance
(mL/min)
Induction Dose
Maintenance Dose
≥ 60
900 mg po twice daily
900 mg po daily
40-59
450 po twice daily
450 mg po daily
25-39
450 mg po once daily
450 mg po every other day
10-24
450 mg every other day
450 twice weekly
< 10 (on hemodialysis)
not recommended
not recommended
Acyclovir (Zovirax®)
Creatinine Clearance
(mL/min)
Normal Dose Regimen
Adjusted Dose Regimen
> 10
400 mg po twice daily
400 mg po twice daily
0 to 10 (post-HD)
400 mg po twice daily
200 mg po twice daily
Foscarnet (Foscavir®)
CrCl
(ml/min/kg)
Induction Dose
(equivalent to 180 mg/kg/day)
> 1.4
60 mg/kg Q 8H
> 1.0 to 1.4
45 mg/kg Q 8H
> 0.8 to 1.0
> 0.6 to 0.8
> 0.5 to 0.6
≥ 0.4 to 0.5
< 0.4
50 mg/kg Q
12H
40 mg/kg Q
12H
60 mg/kg Q
24H
50 mg/kg Q
24H
Not
recommended
90 mg/kg Q
12H
70 mg/kg Q
12H
50 mg/kg Q
12H
80 mg/kg Q
24H
60 mg/kg Q
24H
50 mg/kg Q
24H
Not
recommended
Maintenance Dose
(equivalent to 90 or 120
mg/kg/day)
90 mg/kg Q
120 mg/kg Q
24H
24H
70 mg/kg Q
90 mg/kg Q
24H
24H
50 mg/kg Q
65 mg/kg Q
24H
24H
80 mg/kg Q
105 mg/kg Q
48H
48H
60 mg/kg Q
80 mg/kg Q
48H
48H
50 mg/kg Q
65 mg/kg Q
48H
48H
Not
Not
recommended
recommended
Compliance, Policy & Regulatory Committee Approval
Reinaldo Rampolla, M.D.
Medical Director, Lung Transplantation
__________________________________________
George E. Loss, Jr., Ph.D., M.D.
Chief, Multi-Organ Transplant Institute
11/21/2013
Date
12/5/2013
Date
12/11/2013 ______
Date