title: Drug interactions involving antiepileptic drugs: assessment of the consistency among three drug compendia and FDA-approved labels.
abstract: Interactions of antiepileptic drugs (AEDs) with other substances may lead to adverse effects and treatment failure. To avoid such interactions, clinicians often rely on drug interaction compendia. Our objective was to compare the concordance for twenty-two AEDs among three drug interaction compendia (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug Administration-approved product labels. For each AED, the overall concordance among data sources regarding existence of interactions and their classification was poor, with less than twenty percent of interactions listed in all four sources. Concordance among the three drug compendia decreased with the fraction of the drug excreted unchanged and was greater for established inducers of hepatic drug-metabolizing enzymes than for the drugs that are not inducers (R-square=0.83, P<0.01). For interactions classified as contraindications, major, and severe, concordance among the four data sources was, in most cases, less than 30%. Prescribers should be aware of the differences between drug interaction sources of information for both older AEDs and newer AEDs, in particular for those AEDs which are not involved in hepatic enzyme-mediated interactions.
authors.affiliation: Department of Neurology, Agnes Ginges Center of Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address: dekstein@hadassah.org.il.
authors.forename: Dana
authors.initials: D
authors.lastname: Ekstein
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: matir24@gmail.com.
authors.forename: Matanya
authors.initials: M
authors.lastname: Tirosh
authors.affiliation: Myers-JDC-Brookdale Institute, Jerusalem, Israel. Electronic address: eyal.yonatan@gmail.com.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Eyal
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel; Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel; David R. Bloom Centre of Pharmacy and Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology and Therapeutics, The Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: sarae@ekmd.huji.ac.il.
authors.forename: Sara
authors.initials: S
authors.lastname: Eyal
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D062313:Databases, Pharmaceutical / Q000592:standards*; D004347:Drug Interactions; D004348:Drug Labeling / Q000592:standards*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000927:Anticonvulsants; D003577:Cytochrome P-450 Enzyme System
keywords: Antiepileptic drugs; Compendia; Cytochrome P450; Drug information; Drug interactions