General Information

Valcyte tablets have been approved by the FDA for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Valcyte is an oral prodrug of Cytovene, a currently approved and widely prescribed anti-CMV medication.

The active ingredient in Valcyte is valganciclovir, which exists as a mixture of two diastereomers (compounds with the same atoms, but in different arrangements). In the body, the diastereomers are converted to ganciclovir, which inhibits the replication of human cytomegalovirus.

CMV belongs to the family of herpes viruses. The virus remains inactive in individuals with normal immune function; however, it can cause illness in those with compromised immune systems, such as individuals with AIDS or patients taking post-transplant immunosuppressants. In patients with HIV/AIDS, the most common form of CMV is CMV retinitis, an infection of the eye that can lead to blindness.

Mechanism of Action

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir that exists as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human cytomegalovirus in vitro and in vivo.

In CMV-infected cells, ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase, pUL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly. As the phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by ganciclovir triphosphate (from Valcyte Prescribing/Label Information).

Side Effects

Adverse events reported from two trials of Valcyte include (but are not limited to) the following:

• diarrhea
• nausea
• pyrexia (fever)
• neutropenia (decreased number of white blood cells)
• anemia
• headache
• vomiting
• abdominal pain
• insomnia
• retinal detachment

Clinical Trial Results

A randomized, open-label, controlled trial evaluated 160 subjects with AIDS and newly diagnosed CMV retinitis. Subjects were randomized to receive treatment with either Valcyte tablets or intravenous ganciclovir solution (Cytovene-IV). The median age of the participants was 39 years, the median baseline HIV-1 RNA was 4.9 log10 and the median CD4 cell count was 23 cells/mm3. A determination of CMV retinitis progression by the masked review of retinal photographs taken at baseline and week four was the primary outcome measurement of the three-week induction therapy. At four weeks, Valcyte tablets were found to have comparable efficacy for induction therapy when evaluated against Cytovene-IV.