Fomivirsen
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.
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