Possible Interaction Between Topical Terbinafine and Acenocoumarol

Potential therapeutic hazards due to drug–drug interaction between topically and systemically coadministered medications

“…Some factors may influence the likelihood of DDI between topically and systemically administered medications and they are as follows: (1) percentage of body surface area to which the topical formulation is applied; (2) age of the patient – the very old and very young are more likely to exhibit DDI; (3) genetic factors may affect the magnitude of DDI (eg, DDI between timolol eye drops and oral quinidine is dependent on CYP2D6 phenotype; poor metabolizers have a higher risk for DDIs with a low systemic concentration of a topical imidazole derivative than extensive metabolizers do);5,17 (4) method of application-medications applied under occlusion are more likely to cause DDI; (5) condition of the stratum corneum-topical formulations applied to mucous membranes, genital skin, or thin, macerated or ulcerated skin are more susceptible to be systemically absorbed; and (6) other concomitantly used medications are also involved in the DDI mechanism, eg, topical terbinafine (precipitant drug) impaired CYP2D6-mediated drug metabolism of diltiazem and elevated diltiazem level increased the magnitude of CYP3A4-mediated metabolism inhibition toward acenocoumarol (object drug) 9…”

“…Methods used for judging whether there are DDIs between topically and systemically administered medications are as follows: (1) pharmacokinetic interaction study; (2) randomized controlled clinical trials focusing on overall tolerability of topical formulation with concomitant use of systemically administered medication; and (3) case analysis by using the Horn Drug Interaction Probability Scale or Naranjo scale 9,10,18…”