Surveillence of Drug Metabolizing Enzyme and Transporter-Based Drug-Drug Interaction Potential in Patients Receiving Oral Antineoplastic Agents

Surveillence of Drug Metabolizing Enzyme and Transporter-Based Drug-Drug Interaction Potential in Patients Receiving Oral Antineoplastic Agents.

Authors: S. J. Bowlin, F. Xia, W. Wang, K. D. Robinson, E. J. Stanek

BACKGROUND: Enzyme-targeted oral antineoplastic drugs (OAD) have advanced cancer care but are expensive and have narrow therapeutic indices. Drug metabolizing enzymes and transporters are key to OAD disposition, and create potential for drug-drug interactions (DDIs) that may reduce effectiveness or increase toxicity of OADs. We conducted a retrospective surveillance of DDI burden and co-prescribing (Co-Rx) patterns among patients on OADs.

METHODS: We used deidentified pharmacy claims to identify patients prescribed 1 of 9 OADs (data shown for 6) from January 2008 to May 2010, with the date of the first claim as the index date. We searched for DDI drug use for the 12-months including and after the index date; Co-Rx was defined as ≥1 overlapping days of supply with the OAD. Drugs with DDI potential mediated through CYP P450 or p-glycoprotein pathways were identified from OAD labels and other published sources. We calculated statistics for Co-Rx, and categorized DDIs as either potentially reducing OAD effectiveness or increasing toxicity.

RESULTS: Co-Rx rates are presented below. Co-Rx pattern data relate to the Co-Rx group they are listed under.

CONCLUSION: This surveillance of pharmacy claims found the frequency of potential DDIs in patients on OADs high with interactions that may reduce OAD effectiveness or increase toxicity. Several OADs had high proportions of Rx days with Co-Rx. Clinical implications of this warrant more investigation, and may provide opportunities for expanded DDI monitoring in those taking OADs.

Citation: Clin Pharmacol Ther 91: S57-S58.

Link: http://www.nature.com/clpt/journal/v91/n1s/pdf/clpt2011361a.pdf