Page 238 - WSAVA2018
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 25-28 September, 2018 | Singapore
Acyclovir (ACV) has relatively low antiviral potency against FHV-1, poor bioavailability, and is potentially
toxic when systemically administered to cats. Oral administration of 50 mg/kg acyclovir to cats was associated with peak plasma levels of only approximately one third required for this virus. Common signs of toxicity are referable to bone marrow suppression. However, acyclovir is also available as a 3% ophthalmic ointment
in some countries. In one study in which a 0.5% ointment was used 5 times daily, the median time to resolution
of clinical signs was 10 days. Cats treated only 3 times daily took approximately twice as long to resolve and did so only once therapy was increased to 5 times
daily. Taken together, these data suggest that very frequent topical application of acyclovir may produce concentrations at the corneal surface that do exceed
the reported concentration required for this virus but
are not associated with toxicity. There are also in vitro data suggesting that interferon exerts a synergistic effect with acyclovir that could permit an approximately 8-fold reduction in acyclovir dose. In vivo investigation and validation of these data are needed.
Valacyclovir (VCV) is a prodrug of acyclovir that, in humans and cats, is more efficiently absorbed from
the gastrointestinal tract compared with acyclovir and
is converted to acyclovir by a hepatic hydrolase. Its safety and efficacy have been studied in cats. Plasma concentrations of acyclovir that surpass the IC50 for FHV-1 can be achieved after oral administration of this drug. However, in cats experimentally infected with FHV-1, valacyclovir induced fatal hepatic and renal necrosis, along with bone marrow suppression, and did not reduce viral shedding or clinical disease severity. Therefore, despite its superior pharmacokinetics, valacyclovir should never be used in cats.
Ganciclovir (GCV) appears to be at least 10-fold more effective against FHV-1 compared with acyclovir. It
is available for systemic (IV or PO) and intravitreal administration in humans, where it is associated with greater toxicity than acyclovir. Toxicity is typically evident as bone marrow suppression. It has been released as a new topical antiviral gel in humans. There are no reports of its safety or efficacy in cats as a systemic or topical agent, although anecdotal reports from Europe (where it is much less expensive) are very promising.
Famciclovir (FamvirĀ® and generic) is a prodrug of penciclovir; however metabolism of famciclovir
to penciclovir in humans is complex; requiring di- deacetylation, in the blood, liver, or small intestine, and subsequent oxidation to penciclovir by aldehyde oxidase in the liver. Unfortunately, hepatic aldehyde oxidase activity is nearly absent in cats. This has necessitated cautious extrapolation to cats of data generated in humans. Indeed data to date suggest that famciclovir and penciclovir pharmacokinetics in the cat are
extremely complex and likely nonlinear. For example, an approximately 6-fold increase in dose produced only an approximately 3-fold increase in plasma concentration. However, in a masked, prospective, placebo-controlled study of efficacy, experimentally infected cats receiving 90 mg/kg famciclovir TID had significantly reduced clinical signs, serum globulin concentrations, histologic evidence of conjunctivitis, viral shedding, and serum FHV-1 titers, as well as increased goblet cell density. Importantly, no important adverse clinical, hematologic or biochemical changes were associated with famciclovir administration. More recently, we have shown that 90 mg/kg PO BID produces almost identical plasma and tear concentrations as did the TID dose that was so successful. Do not compound, do not taper the dose when seeing improvement. Rather, treat beyond clinical resolution and then stop.
Cidofovir (CDV) is commercially available only in injectable form in the USA but has been studied as
a 0.5% solution applied topically twice daily to cats experimentally infected with FHV-1. Its use in these cats was associated with reduced viral shedding and clinical disease. Its efficacy at only twice daily (despite being virostatic) is believed to be due to the long tissue half- lives of the metabolites of this drug. There are occasional reports of its experimental topical use in humans being associated with stenosis of the nasolacrimal drainage system components and, as yet, it is not commercially available as an ophthalmic agent in humans. Therefore, at this stage there are insufficient data to support its long term safety as a topical agent in cats.
The literature regarding lysine has become very interesting recently with some data that at first glance appear contrary to earlier study outcomes which suggested efficacy. This requires a more detailed assessment.
Lysine limits the in vitro replication of many viruses, including FHV-1. The antiviral mechanism is unknown; however, many investigators have demonstrated that concurrent depletion of arginine is essential for lysine supplementation to be effective. This finding suggests that lysine exerts its antiviral effect by antagonism of arginine. Meanwhile, results of 2 early independent in vivo studies have supported the clinical use of l-lysine
in cats. Lysine-treated cats undergoing primary herpetic disease had significantly less severe conjunctivitis than cats that received placebo, while latently infected adult cats receiving lysine had reduced viral shedding. In both studies, plasma arginine concentrations remained in the normal range, and no signs of toxicity were observed, despite notably elevated plasma lysine concentrations in treated cats. A subsequent study examined the effects of lysine in 144 shelter cats receiving oral boluses of 250 mg (kittens) or 500 mg (adult cats) of lysine once daily

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