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

Abstract

To evaluate compounded famciclovir suspensions for accuracy, precision, and consistency in drug content. Two compounded famciclovir concentrations were evaluated (250 and 400mg/mL, 30 preparations total from nine 503A compounding pharmacies) with U.S. Food and Drug Administration (FDA)-approved famciclovir tablets as control. Drug quantification via high-performance liquid chromatography (with famciclovir reference standard and pramipexole internal standard) was performed at 0, 14, and 28days with concentrations of 90%-110% of labeled dose considered acceptable (US Pharmacopoeia standards). FDA-approved tablets from three different manufacturers were found to be accurate and precise with acceptable drug content. A significantly greater mean deviation from labeled content was noted for 400mg/mL suspensions (-52.9%) compared to 250mg/mL suspensions (-18.0%). When assessing time points separately, 15/63 (24%) samples of 250mg/mL and 0/27 (0%) samples of 400mg/mL suspensions met the acceptance standards. Coefficients of variation (CV) in drug content among pharmacy batches ranged from 0.5% to 29%, with 5/10 formulations having significantly lower CV% compared to control (decreased precision). Similarly, drug content changed over time (0-28days) in all compounded formulations, with both downward and upward trends observed (variable consistency). Most compounded famciclovir formulations were inaccurate, imprecise, and inconsistent. FDA-approved famciclovir tablets may be preferred over compounded famciclovir formulations for the management of feline herpesvirus-1. If compounded famciclovir is used in practice, a concentration of 250mg/mL is preferred over 400mg/mL given the lower accuracy of the higher concentration.