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Famciclovir use for ocular, respiratory and dermatologic disease attributed to feline herpesvirus

Thomasy SM, Shull O, et al. Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006-2013). J Am Vet Med Assoc 2016;249(5):526-38.

Clinical signs associated with chronic-active feline herpesvirus type 1 (FHV-1) infection, usually ocular or upper respiratory, and sometimes dermatologic, are  among the most common problems encountered in general feline medical practice, yet no reliably successful, evidence-based treatments are available. Many clinicians rely upon antibiotic and/or anti-inflammatory therapies for patients with active FHV-1, but FHV-1 is a viral disease, and antibiotics are really only useful when a secondary bacterial infection is present.  Some anti-inflammatory medications, due to their immunosuppressive properties, may actually promote or prolong emergence of FHV-1 from the lifelong latency it generally has in most cats.

Famciclovir is an oral prodrug of penciclovir, which is a nucleoside deoxyguanosine analog with potent antiviral activity against several human herpesviruses as well as demonstrated in vitro activity against FHV-1.  The pharmacokinetics of penciclovir following oral administration of famciclovir to cats differs from that in other species, and is complex and nonlinear. Previous studies in cats have demonstrated that one oral dose of 40 mg/kg or 90 mg/kg of famciclovir resulted in similar maximum plasma concentrations of the drug.  Potentially therapeutic concentrations of penciclovir in feline tears has been achieved with oral administration of famciclovir at 40 mg/kg 3 times daily.

Even with low doses of oral famciclovir, penciclovir is significantly more bioavailable to human subjects than cats, who require oral famciclovir in doses an order of magnitude larger than people to achieve about 10% of the penciclovir bioavailability reached in humans with low doses of famciclovir.  In this retrospective case series of 59 client-owned cats with presumed FHV-1 infection, medical records as well as an owner questionnaire were reviewed to determine an optimal dosing regimen for oral famciclovir.

The patients ranged in age from 12 days to 16 years; 36 were either neutered or sexually intact males, and 23 were spayed or sexually intact females. Domestic shorthairs comprised 66% (n=39) of the patients, while 34% (n=20) were purebred. Clinical signs observed included conjunctivitis (86%), keratitis (86%), blepharitis (32%), nasal discharge or sneezing (17%), and dermatitis (7%). Results were compared in terms of resolution of clinical signs and owner satisfaction with treatment between groups receiving low-dose (approximately 40 mg/kg 3 times daily) and high-dose (approximately 90 mg/kg 3 times daily) oral famciclovir. Commercial oral famciclovir tablets were used, so there was some variation from the ideal targeted doses, depending on the body weight of the patient. Treatment of each patient with oral famciclovir was started and discontinued at the discretion of the attending clinician. Disease severity was scored as mild, moderate, or severe based on the information in the medical record.

The medical records of the patients indicated that clinical improvement was evident in 85% of the patients (n=50) who received famciclovir at either 40 mg/kg 3 times daily or 90 mg/kg 3 times daily, with or without other concurrent topical or systemic treatments. Of the 32 owners who responded to the questionnaire, 78% (n=25) said that the clinical signs of FHV-1 improved with the treatments used.  Almost three-quarters (70%) of reporting owners said they thought famciclovir was the most or second most effective drug their cat received in terms of reducing clinical signs of FHV-1. Those patients receiving the high-dose famciclovir regimen had significantly greater clinical improvement, significantly shorter time to clinical improvement, and significantly shorter duration of treatment than those in the low-dose group. Treatment duration with the famciclovir within the study group varied widely, anywhere from 4 days to 882 days, but typically those cats in the low-dose group were treated for about 36 days, and those in the high-dose group were treated for about 14 days.

Most cats (83%; n=49) experienced no adverse effects, and this included 8 patients who received famciclovir for greater than 3 months, one of whom took the drug for 2.4 years.  Gastrointestinal signs such as diarrhea, anorexia, vomiting and weight loss were the most common problems observed in the 10 cats who did experience potential side effects from famciclovir administration. One cat became polydipsic and while the polydipsia resolved with withdrawal of the famciclovir, the cat’s urine specific gravity remained low.  Although this patient may have had preexisting renal disease, the authors recommend that famciclovir be used judiciously in patients with preexisting renal disease and all cats over 10 years of age, which were considered geriatric for the purposes of the study, possibly at a decreased dose frequency as is recommended in humans receiving the drug. Renal parameters and clinical signs should be monitored closely in such patients before and during treatment with famciclovir.  Famciclovir has a much greater safety margin in cats compared with valacyclovir, the prodrug of acyclovir, which has serious adverse effects on kidney, liver, and bone marrow health in cats, and should not be used in this species.

Juvenile cats (< 7 months of age) enrolled in the study experienced no adverse effects, and some of these patients were only 12 days old; tablets had to be split for many of these patients due to their low body weight.  All 12 juvenile cats enrolled in the study became well rapidly, with clinical improvement reported within 3 to 14 days.  These findings suggest that primary FHV-1 infection causing disease may be particularly amenable to famciclovir therapy.

As a retrospective case series, this study has inherent limitations.  The authors recommend that prospective, masked, controlled studies to evaluate the safety and efficacy of famciclovir therapy in cats with confirmed active FHV-1 infection be conducted, including trials that could determine whether a dosage of 90 mg/kg versus 40 mg/kg orally three times daily would facilitate increased efficacy and shorter treatment time. [PJS]

See also:

Litster AL, Lohr BR, et al.  Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter.  Vet J 2015;203:199-204.