Fomivirsen (Vitravene), an anti-CMV agent, is the first antisense oligonucleotide to be approved by the U. S. Food and Drug Administration (FDA) as an antiviral therapy. Fomivirsen is an oligonucleotide complemen-tary to the major immediate early region 2 (IE2) of CMV mRNA. By binding to IE2 mRNA, fomivirsen prevents its translation to protein and thereby blocks viral replication. Because this mechanism of action isdifferent from that of other antiviral agents, cross-resistance with other drugs used to treat CMV is unlikely.
Fomivirsen is injected directly into the vitreous humor of the eye. Animal studies have shown that this drug ac-cumulates in the retina and iris over 3 to 5 days and is cleared from the vitreous humor within 7 to 10 days. Fomivirsen exhibits minimal systemic absorption and is degraded locally by cellular exonucleases.
Fomivirsen is used to treat CMV retinitis in patients with AIDS who have not responded to other treatments or in whom other treatments are contraindicated. It ap-pears to be at least as effective as other treatments and produces fewer side effects. Because CMV retinitis is often associated with CMV infection elsewhere in the body, patients undergoing treatment with fomivirsen should be monitored for extraocular CMV disease.
Iritis, which affects up to 25% of patients undergoing fomivirsen therapy, can be managed with topical corti-costeroids. Vitreitis and increased intraocular pressure may also result from fomivirsen administration. Fomivirsen is contraindicated in patients who have been treated with cidofovir within the previous 2 to 4 weeks because cidofovir increases the risk of ocular in-flammation.