Prior Auth Protocol

FDA Approved Indications:

Adult patients

For the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS)
For the prevention of CMV disease in kidney, heart, or kidney-pancreas transplant patients at high risk (donor CMV seropositive/recipient CMV seronegative [D+/R-])

Pediatric patients

For the prevention of cytomegalovirus (CMV) disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk

Health Net Approved Indications and Usage Guidelines:

Treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)

OR

Prophylaxis of CMV disease in solid organ transplant patients

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and usage guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Based on the 2009 Solid Organ Transplant Guidelines for CMV prophylaxis and the 2010 International guidelines, 3 to 6 months of prophylaxis therapy is recommended for donor+/recipient- heart transplant recipients and kidney/pancreas recipients. Three months of prophylactic therapy is recommended for recipient+ heart transplant recipients.
Based on the results of the IMPACT study, Valcyte prophylaxis for 200 days in kidney transplant patients resulted in a reduction in CMV disease. At 2 years post-transplant, CMV disease occurred in significantly less patients in the 200- vs. the 100-day group: 21.3% vs. 38.7%, respectively (P<0.001).
Although Valcyte is not FDA approved for the prevention of CMV disease in liver transplant patients, consensus treatment guidelines support the use of Valycte in this transplant type.
Data supporting the use of Valcyte for lung transplant patients come from Finlen et al, who concluded that 12 months of Valcyte prophylaxis compared with 3 months provided a protective benefit with a CMV incidence of 12% vs 55% respectively (HR 0.13, CI: 0.03-0.61, p = 0.009). In another randomized clinical trial by Palmer et al, extending the duration of Valcyte prophylaxis from 3 months to 12 months decreased the incidence of CMV disease from 64% to 10% (p < 0.001).
The prescribing information contains a boxed warning regarding potential toxicity including severe leukopenia, neutropenia, pancytopenia, bone marrow aplasia, aplastic , anemia and thrombocytopenia. It notes that animal studies have demonstrated carcinogenicity, teratogenicity and caused aspermatogenesis.
Per CDC guidelines for the treatment of CMV retinitis, Valcyte may be used in combination with ganciclovir intraocular implant for patients with immediate sight-threatening lesions (adjacent to the optic nerve or fovea).
The safety and efficacy of Valcyte for oral solution and tablets have not been established in children for prevention of CMV disease in pediatric liver transplant patients, in kidney transplant patients less than 4 months of age, in heart transplant patients less than 1 month of age, in pediatric AIDS patients with CMV retinitis, and in infants with congenital CMV infection
In 2010, the FDA added an upper limit to pediatric dosing calculation to prevent Valcyte overdoing in children with low body weight, surface area and below normal serum creatinine

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
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* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Valcyte^R (valganciclovir)	CMV Retinitis Induction 900 mg PO BID for 21 days Maintenance 900 mg PO QD Prevention of CMV disease in lung transplant (17 years and older) 900 mg PO per day starting within 10 days of transplant Prevention of CMV disease in heart, liver, kidney, and kidney-pancreas transplant (17 years and older) 900 mg PO per day starting within 10 days of transplant Prevention of CMV disease in kidney transplant (4 months to 16 years of age) Dose once a day within 10 days of transplant until 200 days post transplant according to dosage algorithm (dose varies based on BSA and CrCl). Maximum dose of 900 mg per day Prevention of CMV disease in heart transplant patients (1 month to 16 years of age) Dose once a day within 10 days of transplant until 100 days post transplant according to dosage algorithm (dose varies based on BSA and CrCl). Maximum dose of 900 mg per day	CMV Retinitis Induction: One time Maintenance: Length of Benefit Prevention of CMV disease in lung and liver transplant (17 years and older) 12 months Prevention of CMV disease in heart, kidney, and kidney-pancreas transplant (17 years and older) Up to 200 days Prevention of CMV disease in kidney transplant (4 months to 16 years of age) 200 days Prevention of CMV disease in heart transplant patients (1 month to 16 years of age) 100 days

Product Availability:

Tablet: 450 mg
Powder for oral solution: 50 mg/ml

References:

Valcyte [Prescribing Information] South San Francisco, CA: Genentech USA, INC, A Member of Roche Group; April 2015.
Humar A, Snydman D, AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplant recipients. Am J Transplant 2009; 9 (Suppl4):S78-S86.
Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation. Transplantation. 2010;89:779.
Finlen Copeland CA, 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 single-center, long-term follow-up analysis from a randomized, controlled cytomegalovirus prevention trial. J Heart Lung Transplant 2011 Sep;30(9):990-6.
Palmer SM, Limaye AP, Banks M, et al. Extended Valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized controlled trial. Ann Intern Med. 2010;152(12):761-769.
Humar A, Limaye AP, Blumberg EA et al. Extended valganciclovir prophylaxis in D+/R- kidney transplant recipients is associated with long-term reduction in cytomegalovirus: two-year results of the IMPACT study. Transplantation 2010;90(12):1427-31.
Centers for Disease Control and Prevention. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from CDC, the National Institutes of Health and the HIV Medicine Association / Infectious Diseases Society of America. MMWR 2009;58(No.RR-4):57. Available at http://www.cdc.gov/mmwr/pdf/rr/rr5804.pdf. Accessed January 5, 2016.
Valcyte. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed January 5, 2016.
Valcyte. In: DrugPoints^R System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed January 5, 2016.
Valcyte. MedWatch: The FDA Safety Information and Adverse Event Reporting Program Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm225888.htm . Accessed January 5, 2016.