Valganciclovir Hydrochloride and Aortic stenosis

• Generic Name: valganciclovir
• Dosage Forms: n.a.
• Other Brand Names: Valcyte

Initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) of CMV retinitis in HIV-infected adults, including those with acquired immunodeficiency syndrome (AIDS). Also used for management of CMV retinitis in certain HIV-infected pediatric patients.

Like other antivirals, valganciclovir is not a cure for CMV retinitis; relapse and/or progression of CMV retinitis possible during or following valganciclovir therapy.

Retinitis is the most common clinical manifestation of CMV end-organ disease in HIV-infected patients; ideally should be managed in consultation with an ophthalmologist familiar with diagnosis and treatment of retinal diseases.

Select antiviral regimen for initial treatment of CMV retinitis in HIV-infected individuals based on location and severity of CMV retinal lesions, severity of underlying immunosuppression, concomitant drug therapy, and patient’s ability to adhere to the treatment regimen. Select antiviral regimen for maintenance therapy based on location of CMV retinal lesions, vision in contralateral eye, patient's immunologic and virologic status, and patient's response to antiretroviral therapy.

For management of immediate sight-threatening CMV retinal lesions (e.g., within 1.5 mm of the fovea) in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the preferred regimen is initial treatment (induction therapy) with intravitreal ganciclovir or intravitreal foscarnet (1–4 doses given over a period of 7–10 days) in conjunction with oral valganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily). One alternative regimen recommended by these experts for sight-threatening CMV retinitis in HIV-infected adults and adolescents is intravitreal ganciclovir or intravitreal foscarnet (1–4 doses given over a period of 7–10 days) in conjunction with IV ganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily). Systemic antivirals (without an intravitreal antiviral) usually adequate for management of CMV retinitis in patients with only small peripheral lesions.

For management of CMV retinitis in HIV-infected pediatric patients, CDC, NIH, IDSA, and others state that IV ganciclovir is drug of choice for initial treatment (induction therapy) and one of several options for maintenance therapy (secondary prophylaxis). These experts state that oral valganciclovir may be considered in older children and adolescents transitioning from IV ganciclovir to oral valganciclovir to complete treatment and/or for maintenance therapy following improvement of retinitis.

Because of risk of relapse, chronic maintenance therapy (secondary prophylaxis) of CMV retinitis usually continued until immune reconstitution occurs as a result of effective antiretroviral therapy. CDC, NIH, and IDSA state that discontinuance of maintenance therapy of CMV retinitis can be considered in HIV-infected adults and adolescents if CMV lesions have been treated for ≥3–6 months and are inactive and there has been a sustained (i.e., 3–6 months) increase in CD4+ T-cell count to >100/mm3 in response to antiretroviral therapy. Although safety of discontinuing maintenance therapy of CMV retinitis in HIV-infected pediatric patients not well studied, discontinuance of such therapy can be considered in those receiving antiretroviral therapy who have a sustained (i.e., >6 months) increase in CD4+ T-cell percentage to >15% (children <6 years of age) or increase in CD4+ T-cell count to >100/mm3 (children ≥6 years of age).

If maintenance therapy of CMV is discontinued, continue regular ophthalmologic monitoring (optimally every 3–6 months) for early detection of CMV relapse or immune reconstitution uveitis. If CD4+ T-cell count decreases to <100/mm3 (adults, adolescents, children ≥6 years of age) or CD4+ T-cell percentage decreases to <15% (children <6 years of age), reinitiate CMV retinitis maintenance therapy.

Although safety and efficacy not established for management of extraocular CMV infections, has been recommended as an alternative for CMV esophagitis or colitis in HIV-infected adults.

CDC, NIH, and IDSA state that IV ganciclovir usually the preferred antiviral in HIV-infected adults with CMV GI disease, but transition to oral valganciclovir may be considered for management of CMV GI disease when patient can tolerate and absorb oral drugs. Also can consider valganciclovir for initial management of CMV esophagitis or colitis in patients with GI symptoms that do not interfere with oral absorption.

Although safety and efficacy not established, has been used for management of symptomatic congenital CMV disease.

Transmission of CMV from infected mothers to their fetuses occurs as a result of maternal viremia and transplacental infection; perinatal infection also can occur from exposure to CMV shedding in mother's genital tract. Approximately 10% of neonates with congenital CMV infection are symptomatic at birth; mortality is about 10% and approximately 50–90% of symptomatic surviving neonates experience substantial morbidity (e.g., mental retardation, sensorineural hearing loss, microcephaly, seizures). Risk of congenital CMV infection resulting from primary maternal CMV infection may be higher and the disease more severe than that resulting from reactivation of maternal CMV infection.

AAP and others recommend valganciclovir be considered in neonates with moderate to severe symptomatic congenital CMV disease (with or without CNS involvement) when an antiviral indicated. Regimen of IV ganciclovir either alone or followed by valganciclovir also has been used.

CDC, NIH, IDSA, and others state consider IV ganciclovir for initial treatment of symptomatic congenital CMV disease with CNS involvement in HIV-exposed or HIV-infected infants.

Antivirals not usually recommended for neonates with asymptomatic congenital CMV infection or only mildly symptomatic infection without evidence of CNS involvement.

Prophylaxis to prevent CMV infection and disease in adult kidney, heart, and kidney-pancreas transplant recipients considered at high risk for the disease (CMV-seronegative recipient/CMV-seropositive donor).

Prophylaxis to prevent CMV infection and disease in pediatric kidney transplant recipients 4 months to 16 years of age and pediatric heart transplant recipients 1 month to 16 years of age considered at high risk (CMV-seronegative recipient/CMV-seropositive donor).

Although safety and efficacy not established, has been used for preemptive treatment of CMV infection in solid organ transplant recipients (kidney, heart, pancreas).

Has been recommended for prophylaxis or preemptive treatment of CMV infection in liver transplant recipients; however safety and efficacy not established in adult or pediatric liver transplant patients and low efficacy reported in a study in adults.

Has been used for prophylaxis or preemptive treatment of CMV infection and disease in hematopoietic stem cell transplant (HSCT) recipients.