Ganciclovir Sodium and Bone marrow suppression

• Generic Name: ganciclovir
• Dosage Forms: n.a.
• Other Brand Names: Cytovene

Initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) of CMV retinitis in immunocompromised patients, including HIV-infected adults. Also used for management of CMV retinitis in HIV-infected pediatric patients.

Like other antivirals, ganciclovir is not a cure for CMV retinitis; stabilization or improvement of ocular manifestations may occur, but relapse and/or progression of CMV retinitis possible during or following ganciclovir 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. Data are limited regarding use of intravitreal antivirals in children; intravitreal injections are impractical in most children.

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 used in immunocompromised patients for management of CMV GI disease, pneumonitis, encephalitis, or other CMV infections.

CDC, NIH, and IDSA state that IV ganciclovir usually is the preferred antiviral for initial management of CMV GI disease in HIV-infected adults and transition to oral valganciclovir may be considered when patient can tolerate and absorb oral drugs.

For management of well-documented CMV pneumonitis in HIV-infected adults, CDC, NIH, and IDSA state that either IV ganciclovir or IV foscarnet is a reasonable choice.

A combination regimen of IV ganciclovir and IV foscarnet has been used for management of CMV neurologic disease (e.g., CMV encephalitis or myelitis), and is recommended by CDC, NIH, IDSA, and others for such infections in HIV-infected individuals.

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 that oral 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 oral valganciclovir also has been used in neonates with symptomatic congenital CMV disease.

CDC, NIH, IDSA, and others state that IV ganciclovir can be considered 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 solid organ transplant recipients, bone marrow transplant (BMT) recipients, and hematopoietic stem cell transplant (HSCT) recipients at high risk for the disease.

Has been used for preemptive treatment of CMV infection and disease in transplant recipients.

Although optimal regimens for management of progressive outer retinal necrosis caused by VZV not identified, CDC, NIH, and IDSA recommend that such infections in HIV-infected adults and adolescents be treated with at least one IV antiviral (acyclovir, ganciclovir, foscarnet, cidofovir) used in conjunction with at least one intravitreal antiviral (ganciclovir or foscarnet). Some experts recommend IV ganciclovir and/or IV foscarnet used in conjunction with intravitreal ganciclovir and/or intravitreal foscarnet. Prognosis for visual preservation in patients with progressive outer retinal necrosis caused by VZV is poor; such infections should be managed in consultation with an ophthalmologist.