Drug content on receipt and over time for compounded formulations of famciclovir

Abstract

Objectives The aim of this study was to determine famciclovir content (strength) in compounded formulations and to determine if potency changed over time. Methods Four concentrations of oral oil suspension in three distinct flavors, three concentrations of oral paste, three chew treats and 62.5 mg tablets from one compounding pharmacy were evaluated for famciclovir content. Specific sample preparation procedures were used for each drug formulation prior to determination of famciclovir content through mass spectrometry tandem liquid chromatography. Analysis was performed on arrival from the compounder and on days 7, 14, 28, 56 and 120. Samples were run in triplicate and concentration determined by comparison with a standard curve. Content was considered appropriate if within 90–110% of the labeled concentration. Results On arrival from the compounding pharmacy, 5/12 oral oil suspensions of varying concentrations were <90% of the labeled concentration and 3/3 oral pastes were >110%. Famciclovir content in oil suspensions ranged from 72% to 118% of the label value while oral pastes ranged from 95% to 202% of the label concentration over the 120 study days, and all concentrations varied in an unpredictable fashion. Tablets contained 90–110% of the labeled value throughout the study period. Chew treats could not be successfully analyzed. Conclusions and relevance This study found substantial variation in famciclovir content in the compounded products evaluated, which, in turn, raises concerns that substandard dosing could result in lack of efficacy or a failed treatment trial. Drug toxicity might also be encountered. Veterinarians must be aware that while compounded medications can improve compliance, they might not deliver the drug dose expected.

Evaluation of compounded cidofovir, famciclovir, and ganciclovir for the treatment of feline herpesvirus ocular surface disease in shelter‐housed cats

“…Two recent studies have assessed actual concentrations of compounded liquid famciclovir relative to the labeled concentration (from unidentified veterinary compounding pharmacies). 47,48 While one of these prior studies detected wide variability in 400 mg/ml labeled compounded medications, accuracy was generally higher in 250 mg/ml compounded medications. 47 The second study demonstrated variable (increasing and decreasing) famciclovir concentrations over time, for compounded famciclovir suspensions obtained from a single unidentified compounding pharmacy.…”

“…47 The second study demonstrated variable (increasing and decreasing) famciclovir concentrations over time, for compounded famciclovir suspensions obtained from a single unidentified compounding pharmacy. 48 To ensure compounded medication accuracy in the present study, certificates of analysis for each compounded medication were obtained from an independent external laboratory with all concentrations falling within the USP standard of 90%-110% of target drug concentrations. 47 Medications were also ordered in small batches to minimized potential temporal variation in drug concentrations due to prolonged storage.…”

“…One potential explanation for the lack of efficacy of famciclovir in this clinical trial is due to the use of a compounded famciclovir suspension instead of FDA approved famciclovir tablets. Two recent studies have assessed actual concentrations of compounded liquid famciclovir relative to the labeled concentration (from unidentified veterinary compounding pharmacies) 47,48 . While one of these prior studies detected wide variability in 400 mg/ml labeled compounded medications, accuracy was generally higher in 250 mg/ml compounded medications 47 .…”

Variable accuracy, precision, and consistency of compounded famciclovir formulated for management of feline herpesvirus‐1 in cats

“…In contrast, none of the generic famciclovir tablets were inaccurate (0/42 samples, 0%), highlighting the difference between FDA‐approved medications—prepared under good manufacturing principles and undergoing stringent analyses to assess drug content, stability, and safety—and compounded formulations of drugs, that do not have to adhere to such regulations to assure quality 16 . In fact, poor accuracy in compounded formulations has been reported in veterinary medicine, as exemplified by studies on compounded doxycycline, 12 cyclosporine, 10 and famciclovir 17 . For the latter, a recently published study evaluated drug content in different formulations of famciclovir (chews, treats, pastes, suspensions, tablets) compounded from a single pharmacy; as a comparison, our study focused on a single type of formulation (oil suspension) but from multiple compounding pharmacies.…”

“…16 In fact, poor accuracy in compounded formulations has been reported in veterinary medicine, as exemplified by studies on compounded doxycycline, 12 cyclosporine, 10 and famciclovir. 17 For the latter, a recently published study evaluated drug content in different formulations of famciclovir (chews, treats, pastes, suspensions, tablets) compounded from a single pharmacy; as a comparison, our study focused on a single type of formulation (oil suspension) but from multiple compounding pharmacies. Both studies showed significant variation and deviation in measured drug content from labeled drug content, a finding confirmed in various compounded formulations and multiple compounding pharmacies.…”