To the Editor:Amorolfine, a morpholine derivative, is a topical antifungalagent active against yeasts, dermatophytes, and moulds. Itblocks and depletes ergosterol and accumulations of ignos-terol in the fungal cytoplasmic membrane. Amorolfine has alow systemic absorption and its free fraction seems to beinactivated rapidly [1]. Acenocoumarol, an anticoagulantdrug, inhibits activation of vitamin-K-dependent clottingfactors. It is metabolized in the liver by cytochrome P450.Interactions between topicallyadministered antifungal drugsand orally administered anticoagulant agents could increasethe risk of hemorrhaging and bleeding [2]. However, fewcases have reported an increase in International NormalizedRatio (INR) values. We describe two cases of interactionbetween amorolfine used topically and acenocoumarol.Case 1In May 2009, a 60-year-old white woman came for a check-up at the Hematology Department. She had previously beendiagnosed with arterial hypertension, dyslipidemia, andnon-insulin-dependent diabetes mellitus. She had been re-ceiving acenocoumarol treatment for a mechanical aorticvalve prosthesis since 1994. She reported no significantchanges in her diet or treatment regimen (carvedilol, fluvas-tatin, metformin, glibenclamide). In April 2009, the patientwas diagnosed with onychomycosis of the fingernail. Shehad begun treatment with amorolfine (Odenil 5 % naillacquer) once every 2 weeks. One month later, and aftertwo applications of amorolfine, her INR increased to 7.7.Two weeks later, the patient reapplied two new doses ofamorolfine and her INR increased again to 5.9 (Table 1).Case 2In October 2010, a 71-year-old white woman came for acheckup at the Hematology Department. She had previouslybeen diagnosed with an overactive bladder, arterial hyper-tension, atrial fibrillation, and Parkinson’s disease. She hadbeen receiving acenocoumarol treatment for mechanicalmitral and aortic valve prostheses since 2001. She reportedno significant changes in diet or treatment regimen (solife-nacin, captopril, furosemide, digoxin, levodopa-carbidopa).In September 2010, the patient was diagnosed with onycho-mycosis of the fingernail. She began treatment with amor-olfine (Odenil 5 % nail lacquer) once every 2 weeks. Fifteendays later, and following two applications of amorolfine, herINR increased to 5.7.In our study, both patients were being treated with aceno-coumarol and multiple drugs. They presented stable INR val-ues within the therapeutic range (2.5–3.5) when they begantreatment with topically administered amorolfine. After one totwodoses,theybothdevelopeda dramaticincreaseinINRwithno evidence of bleeding. In both cases, both drugs werestopped and INR values normalized within 1 week. Up to10 % of topically administered amorolfine can be absorbedsystemically [1]. In addition, different substances have beenreported as potentially increasing its systemic absorption sig-nificantly[3].Also,bothdrugsareextensivelyboundtoplasmaproteins[1,2].Introductionofamorolfinecouldhaveproduceddisplacement of acenocoumarol from plasma-protein-binding