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Famciclovir is an antiviral drug used in veterinary medicine predominantly to treat cats suffering from feline herpes virus and FHV (feline viral rhinotracheitis). Famciclovir itself is not active in either humans or cats; it is metabolized to an active form, penciclovir. Although there is still some debate about how cats absorb and use this drug, there have been some very persuasive studies that show that famciclovir can be useful to treat cats with clinical disease due to FHV-1.

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Methods: Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis.

Conclusions and relevance: This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.

Population-level management strategies can reduce stress, such as minimizing primary enclosure movement within the facility, which has been associated with a lower risk of URTD [10]. One study highlighted the importance of housing features that promote welfare in reducing stress levels among shelter cats [11]. Another study showed that shelter cats receiving human interactions had a lower incidence of URTD compared to a control group [12]. Other mitigation strategies address known risk factors for URTD in feline populations, including inadequate sanitation practices and overcrowding [13]. Eliminating URTD morbidity completely can be challenging, and utilizing medical treatment to minimize the severity and hasten resolution of clinical signs is important to improving individual animal health and welfare, as well as having population-level impacts. Population monitoring and prompt identification of cats with URTD are critical in the shelter environment to promote population health [14,15]. Supportive care and antimicrobial therapy are common in URTD treatment plans, and one study of North American shelters found that doxycycline and amoxicillin/clavulanic acid were the most frequently chosen antimicrobials for the treatment of URTD in shelter cats [16].

Antiviral therapy has been considered as a promising treatment option for URTD in cats, but to date, clinical evaluation of its use in cats has been limited. The antiviral agent famciclovir and its active metabolite penciclovir have been studied as a treatment for FHV-1 in vitro, in experimental FHV-1 infection, and in naturally occurring URTD in both client-owned and shelter cats. Numerous in vitro studies of penciclovir have documented antiviral efficacy against FHV-1 [17,18,19,20]. In vivo, famciclovir has complex and non-linear pharmacokinetics [21,22,23]. In a pilot study, a famciclovir dose of 40 mg/kg three times daily resulted in variable tear famciclovir concentrations in cats [24], while in another study, a dose of 90 mg/kg q12h achieved plasma and tear concentrations likely to be therapeutic for FHV-1 treatment [23].

Famciclovir has been shown to be effective in treating experimentally FHV-1-infected cats, resulting in lower median clinical disease scores compared to cats receiving placebo [25]. Additionally, the efficacy of oral famciclovir has been reported in two retrospective case series of client-owned cats with suspected or confirmed FHV-1 infection, with minimal adverse effects [26,27]. In contrast to the aforementioned studies, in a recent randomized study of shelter cats with URTD, administration of famciclovir at 30 mg/kg or 90 mg/kg q12h for seven days did not result in improved clinical scores compared to placebo or no treatment but was associated with lower FHV-1 conjunctival shedding on days eight and 15 [28]. Prophylactic oral administration of famciclovir to shelter cats has not been shown to reduce the incidence of URTD [28,29]. Given the current state of clinical equipoise, further studies are needed to clarify the role of famciclovir in the treatment of clinical URTD in shelter cats.

Cat body weight at the time of study enrollment was utilized to determine target dosing of famciclovir between 40 and 90 mg/kg, designed for tablet administration using commercially available products in a shelter setting.

The previously published clinical scoring system on which ours was based was reported in a study investigating the efficacy of a trivalent feline vaccine against FHV-1, feline calicivirus, and feline panleukopenia [30]. Additionally, those authors reported that the scoring system had been approved by the Center for Veterinary Biologicals in the original immunogenicity investigations for the licensure of the vaccine [30]. This scoring system was adapted to remove some redundancy and aid in usefulness for true daily scoring since the previous score assigned weight to the number of days a given clinical sign had been present such that daily scores were not independent observations. In addition to removing the weighting for the duration of clinical signs, we removed some score components: salivation, as it is likely closely linked to ulcer severity, hypothermia, as body temperature is not taken daily in shelter cats, and coughing, as this is likely to be an intermittent clinical sign that could be missed during a short observation period. We also removed the reference to conjunctivitis but retained ocular discharge in the score, and for both the ocular and nasal discharge, retained greater weighting in the score for mucopurulent versus serous discharge. We also retained weighting of oral ulcer severity based on size and number, and lip/nose ulcer severity based on the presence or absence of bleeding.

All 22 cats were included in the intention-to-treat analysis. Major protocol violations were reported for three cats in the famciclovir group. Two cats were withdrawn from the study from shelter A; one cat due to inability to administer any treatments, and the other due to hypersalivation and vomiting after being administered famciclovir. The third cat, from shelter B, was randomized to receive famciclovir, however received a placebo for the duration of enrollment.

Median clinical scores (middle line), interquartile ranges (boxes), and minimum and maximum (whiskers) clinical scores of shelter cats with upper respiratory tract disease randomized to receive famciclovir (a) or placebo (b). Eleven cats were represented on day one in both the famciclovir and placebo groups (intention-to-treat), with cat numbers by day varying on the number of days in the study.

Cats in the famciclovir group had a longer median duration of study enrollment (Table 3). Seven cats in total reached the end of the 21-day study, at which time 2/3 cats in the famciclovir group (clinical scores of 1 and 3) and 2/4 cats in the placebo group (both with clinical scores of 2) still had clinical signs of URTD.

RT-PCR detection results of upper respiratory tract disease pathogens for 21 shelter cats with naturally occurring upper respiratory tract disease enrolled in a randomized, placebo-controlled clinical trial of famciclovir.

These results, reported as an intention-to-treat analysis, are particularly remarkable, given the high number of protocol violations. While protocol violations are not ideal, the persistence of a treatment effect despite them suggests the potential for a clinically relevant outcome. Given the pragmatic design of this study, the observed protocol violations may reflect challenges in the shelter setting. It also could highlight the difficulty in administering famciclovir to cats in this study or aversiveness to medicating, supporting considerate patient selection. This study demonstrates that famciclovir has the potential to benefit shelter cats with URTD, even if some doses are inadvertently missed.

The treatment effect was evident despite two shelter locations with different supportive care protocols and varied administration of antibiotics. When considering the population of cats with URTD reported herein, the low clinical scores observed, the relatively low prevalence of FHV-1 by RT-PCR, and the low viral shedding suggestive of recrudescence of latent infection may have all resulted in an underestimation of the broader treatment effect of famciclovir. It is possible that in cat populations with more severe clinical signs, higher prevalence of FHV-1, and a greater proportion of new FHV-1 infections, treatment with famciclovir may have greater clinical benefit. On the contrary, it is possible that in populations with lower FHV-1 positivity, famciclovir may have no treatment benefit. This study was based on the empirical treatment approach with famciclovir, which we believe will be informative for shelters. Evidence-based decision-making informs the empirical therapy choices often made for URTD in shelter cats, as RT-PCR testing is not routinely performed for all individual shelter cats with URTD.

One difference between our study and a previous randomized study of famciclovir in shelter cats is the duration of treatment [28]. Our study continued treatment for up to 21 days, compared with seven days of treatment in the previous study, where a difference in clinical score was not observed between groups [28]. We planned to continue therapy for up to 21 days based on a previous experimental study of FHV-1 infection [25]. However, given our goal to prevent shelter pathway impediments for cats in the study, the duration of enrollment of individual cats was varied, achieving a median of 18 days treatment in the famciclovir group. The lack of standard duration of enrollment in the study could have resulted in an underestimation of the famciclovir treatment effect. Additionally, a longer duration of famciclovir administration may be indicated in some cats, given that seven cats in this study still had URTD clinical signs at 21 days. Nonetheless, the approach to the duration of therapy adopted in this study, for up to 21 days or until appropriate based on the shelter pathway, is likely practical for shelters to implement. We were unable to directly assess the impact of the treatment on length of stay with this study design, but improvement in clinical signs has the potential to reduce the length of stay for shelter cats with URTD. Since the length of stay is an important outcome measure in shelter cats, it should be investigated in future studies of famciclovir treatment. 041b061a72