Famciclovir substitution for patients with acyclovir-associated renal toxicity

Htwe, Tin Han; Bergman, Scott; Koirala, Janak

doi:10.1016/j.jinf.2008.06.008

Cited by 17 publications

(6 citation statements)

References 7 publications

(3 reference statements)

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“…In humans, famciclovir has been substituted for acyclo-vir in patients with acyclovir-associated renal toxicosis secondary to crystallizing nephropathy. 24 The pharmacokinetics of famciclovir has been assessed in humans with renal compromise, and a decrease in dose frequency is recommended in this patient population. 25 Therefore, despite the low frequency of renal signs in patients of the present study and inability to establish causation, famciclovir should be used judiciously in feline patients with preexisting renal disease, perhaps at a decreased dose frequency as is recommended in humans, and renal variables and clinical signs should be closely monitored in such patients.…”

Section: Discussionmentioning

confidence: 99%

Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006–2013)

Thomasy

Shull

Outerbridge

et al. 2016

javma

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OBJECTIVE To evaluate outcomes for cats treated with orally administered famciclovir 3 times/d for clinical signs attributed to naturally occurring feline herpesvirus type 1 (FHV-1) infection and to assess variables related to owner satisfaction with the treatment. DESIGN Retrospective case series. ANIMALS 59 client-owned cats. PROCEDURES Medical records were reviewed to identify cats treated for presumed FHV-1 infection from 2006 through 2013 with ≥ 1 follow-up visit. Signalment, duration of clinical signs, prior treatment, examination findings, diagnostic test results, concurrent treatments, and outcome data were recorded. Owners were asked to complete a survey regarding patient- and treatment-related variables. Data were compared between cats that received low (approx 40 mg/kg [18 mg/lb]) and high (approx 90 mg/kg [41 mg/lb]) doses of famciclovir, PO, 3 times/d. RESULTS Patient age ranged from 0.03 to 16 years. Conjunctivitis (51/59 [86%]), keratitis (51 [86%]), blepharitis (19 [32%]), nasal discharge or sneezing (10 [17%]), and dermatitis (4 [7%]) were common findings. Clinical improvement was subjectively graded as marked in 30 (51%) cats, mild in 20 (34%), and nonapparent in 9 (15%). Median time to improvement was significantly shorter, and degree of improvement was significantly greater in the highdose group than in the low-dose group. Adverse effects potentially attributable to famciclovir administration were reported for 10 cats. On the basis of survey responses, most (29/32 [91%]) owners were satisfied with their cat's treatment. CONCLUSIONS AND CLINICAL RELEVANCE Famciclovir at the prescribed dosages was associated with improved clinical signs in cats with presumed FHV-1 infection, and few adverse effects were attributed to the treatment. Further studies are needed to assess whether a famciclovir dosage of 90 versus 40 mg/kg, PO, 3 times/d would result in increased efficacy and shorter treatment time.

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Section: Discussionmentioning

confidence: 99%

Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006–2013)

Thomasy

Shull

Outerbridge

et al. 2016

javma

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“…2,36 The published literature lacks information on the safety of substitution with other antiviral agents; however, it has been proposed anecdotally that famciclovir may be a candidate for substitution-at least in patients who develop nephrotoxicity. 37,38 However, famciclovir treatment may still be associated with some risk of neuropsychiatric events. 39 Finally, we strongly recommend the accumulation of more cases similar to our own, thereby allowing us to clarify the nature of adverse valacyclovir-mediated reactions more precisely as well as establish an optimum management strategy, especially regarding appropriate valacyclovir dosing regimens in elderly patients with HZ who barely appear to have a favorable renal function.…”

Section: Discussionmentioning

confidence: 99%

Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia

Murakami

Akimoto

Okada

et al. 2018

dti

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A 66-year-old women with no history of renal disease was admitted due to a coma and acute kidney injury with a serum creatinine level of 7.44 mg/dL which were ascribed to valacyclovir neurotoxicity and nephrotoxicity, respectively. She had received valacyclovir at a standard dosage for the treatment of herpes zoster and was finally discharged, having fully returned to her normal baseline mental status with a recovered serum creatinine level of 0.68 mg/dL. We feel that awareness of this pathology remains a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own. Our experience underscores the pitfalls of administering valacyclovir to elderly patients who barely appear to have a favorable renal function. Several concerns regarding the therapeutic management, including blood purification strategies, that emerged in this case are also discussed.

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“…For example, famciclovir is used as a rescue antiviral drug for human patients with renal toxicosis induced by administration of acyclovir. 32 Furthermore, in a study 9 in which 59 client-owned cats with suspected herpetic disease were treated with famciclovir, only 10 (17%) developed adverse effects potentially attributable to famciclovir; only 1 of those 10 cats had adverse effects referable to the urinary tract (polydipsia without a concurrent decrease in urine specific gravity). Adverse effects were not associated with the dosage of famciclovir (40 or 90 mg/kg, PO, q 8 h) administered in that study.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

Sebbag

Thomasy

Woodward

et al. 2016

ajvr

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TitlePharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir OBJECTIVESTo determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS7 male domestic shorthair cats. PROCEDURESIn a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTSCompared with penciclovir concentrations, BRL42359 concentrations were 5-to 11-fold greater in plasma and 4-to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCEIn cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus. (Am J Vet Res 2016;77:833-845)

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Famciclovir substitution for patients with acyclovir-associated renal toxicity

Cited by 17 publications

References 7 publications

Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006–2013)

Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006–2013)

Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia

Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

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