Author/Editor		Grabnar, Iztok; Locatelli, Igor; Herman, Darja; Peternel, Polona; Stegnar, Mojca; Lainščak, Mitja; Breskvar, Katja; Dolžan, Vita; Mrhar, Aleš
Title		Drug interactions with carbamezapine: a case study on influence on anticoagulation treatment with warfarin
Translated title		Interakcije zdravil s karbamazepinom: primer raziskave vpliva na antikoagulacijsko zdravljenje v varfarinom
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 76, št. Suppl 2
Publication year		2007
Volume		str. II-41-7
Language		eng
Abstract		Background Drug interactions are an important segment of drug related problems. Therefore their evaluation should be an integral component of patient management, especially in elderly patients who often receive multiple medications. In this manuscript drug interactions with emphasis on their relevance and mechanism are reviewed. Additionally, as an example a detailed analysis of induction of warfarin metabolism during co-treatment with carbamazepine is presented. Patients and methods We searched MEDLINE and tertiary sources. 188 patients on warfarin therapy in the maintenance phase were retrospectively analysed to study the interaction of carbamazepine with warfarin. Blood plasma concentrations of warfarin enantiomers and their metabolites were measured by high performance liquid chromatography. Results In patients co-treated with carbamazepine daily warfarin dose necessary to maintain INR in the range between 2.0 in 3.0 was significantly higher (9.00 versus 4.07 mg/day). Despite the difference in daily dose requirement plasma concentrations of warfarin enantiomers were similar, due to the enhanced metabolism of predominantly R-warfarin by cytochrome P450 (CYP) 3A4. Consequently, the concentration of 10-hydroxywarfarin, which isformed by CYP3A4 was 9-times higher. Conclusions With this study relevance and mechanism of carbamazepine interaction with warfarin was assessed. The study confirmed that the need for warfarin dosage adjustment during initiation and discontinuation of carbamazepine treatment is caused by induction of marfarin metabolism, predominantly by CYP3A4.
Summary		Izhodišča Interakcije med zdravili predstavljajo pomemben del težav povezanih z zdravili. Njihovo prepoznavanje mora zato biti sestavni del obravnave bolnikov, zlasti starostnikov, ki običajno jemljejo več zdravil sočasno. V prispevku je podan pregled interakcij med zdravili s stališča njihovega kliničnega pomena in mehanizma. Podrobneje je predstavljena indukcija presnove varfarina pri sočasnem zdravljenju s karbamazepinom. Bolniki in metode Literaturne podatke smo zajemali iz zbirke MEDLINE in terciarnih virov. V retrospektivno raziskavo interakcije med karbamazepinom in varfarinom smo vključili 188 bolnikov v vzdrževalni fazi zdravljenja z varfarinom. Bolnikom smo s tekočinsko kromatografijo visoke ločljivosti v krvni plazmi določili koncentracijo obeh enantiomer varfarina in njunih presnovkov. Rezultati Pri vključenih bolnikih, ki so bili sočasno zdravljeni s karbamazepinom, smo ugotovili, da so dnevni odmerki varfarina potrebni za vzdrževanje INR v intervalu med 2,0 in 3,0 značilno večji (9,00 proti 4,07 mg/dan), kljub temu pa so plazemske koncentracije obeh enantiomer varfarina podobne. Vzrok za to je pospešena presnova zlasti R-varfarina preko citokroma P450 (CYP) 3A4. Posledično je bila 9-krat povišana tudi koncentrctcija 10-hidroksivarfarina, ki nastaja s CYP3A4. Zaključki Z našo raziskavo smo opredelili pomen in mehanizem interakcije med karbamazepinom in varfarinom. Potrdili smo, da je vzrok za potrebo po povečanju odmerka varfarina pri uvedbi zdravljenja s karbamazepinom in zmanjšanja pri njegovi odtegnitvi indukcija presnove predvsem s CYP3A4.
Descriptors		DRUG INTERACTIONS CARBAMAZEPINE WARFARIN