Restriction and Dosing Guidelines
CMV-IG is FDA-approved for the prophylaxis of cytomegalovirus (CMV) disease associated with kidney, lung, liver, pancreas or heart transplantations.1 The additional benefit of CMV-IG when added to effective antiviral agents (e.g ganciclovir, valganciclovir) for CMV prophylaxis in solid organ transplantation is questionable and supporting evidence is limited.2,3 Some centers utilize CMV-IG for prophylaxis but recent international consensus guidelines leave the issue unanswered. They suggest CMV-IG may be considered in addition to antiviral agents for CMV prophylaxis only in heart, lung, and intestinal transplants (Grade III recommendation, expert opinion & descriptive studies).3 Furthermore, current guidelines do not recommend routine use of CMV-IG for the treatment of CMV disease as there are a paucity of data supporting this practice. The data that do exist consists of nonrandomized or retrospective studies primarily evaluating CMV pneumonitis. 3-9 (Please see attached literature review.)
Due to questionable benefit, significant expense, and to ensure the appropriate usage of CMV-IG, the following restrictions for CMV-IG use are proposed:
- CMV-IG may be used without restriction when ordered as part of an approved TNMC CMV prophylaxis protocol (e.g. small bowel transplant). Protocols containing CMV-IG must be submitted and approved by the Pharmacy and Therapeutics Committee.
- Orders for CMV-IG outside of approved protocols require transplant infectious diseases (ID) service review and approval prior to dispensing. The ordering physician is responsible for contacting the transplant ID service.
- If CMV-IG use is approved by the transplant ID service, the transplant ID Service will relay this information to the ordering physician as well as to the pharmacy. If CMV-IG is thought to be inappropriate, the transplant ID Service will provide alternative recommendations and communicate these recommendations to the physician originating the CMV-IG order.
- Transplant ID may decide that a formal consultation is necessary for approval. In this instance, a formal transplant ID consultation will be required for use of CMV-IG.
Suggested dosing guidelines:1,7,8
- CMV pneumonia: 150mg/kg IV on days 1, 4, and 7 in conjunction with ganciclovir IV or other antiviral
- Higher doses and/or additional weekly doses on days 14 and 21 may be considered in critically ill patients
- Dose rounding is recommended to maximize use of vials (available as 2.5g/50ml vial)
- Cytogam [package insert]. King of Prussia, PA: CSL Behring LLC, 2007.
- Hodson EM, Jones CA, Strippoli GFM, Webster AC, Craig JC. Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients (Review). Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005129.
- Kotton CN, Kumar D, Caliendo AM, Asberg A, Chou S, Snydman DR, Allen U, Humar A. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation. 2010;89(7):779-95.
- Baden LR, Bensinger W, Casper C et al. Prevention and Treatment of Cancer Related Infections. NCCN Clinical Practice Guidelines in Oncology. Version 2.2011, updated 06/14/2011. Accessed 11/30/11. Available at http://www.nccn.org/professionals/physician_gls/pdf/infections.pdf
- Ljungman P, Reusser P, de la Camara R et al. Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant. 2004 Jun;33(11):1075-81.
- George MJ, Snydman DR, Werner BG et al. Use of ganciclovir plus cytomegalovirus immune globulin to treat CMV pneumonia in orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG-Study Group. Transplant Proc. 1993 Oct;25(5 Suppl 4):22-4.
- Alexander BT, Hladnik LM, Augustin KM et al. Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients. Pharmacotherapy 2010; 30(6):554-61.
- Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann Intern Med 1988 Nov 15; 109(10):783-8.
- Ljungman P, Engelhard D, Link H et al. Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group. Clin Infect Dis 1992; 14: 831–835.