Twelve-month frequency of drug-metabolizing enzyme and transporter-based drug-drug interaction potential in patients receiving oral enzyme-targeted kinase inhibitor antineoplastic agents

Abstract

Objective: To describe 12-month rates and patterns of coprescription of drugs that potentially create drug-drug interactions (DDIs) through shared metabolic or transport pathways for 9 enzyme-targeted kinase inhibitor oral antineoplastic drugs (OADs).

Patients and methods: We used a deidentified pharmacy claims database identifying patients prescribed dasatinib, erlotinib, everolimus, imatinib, lapatinib, nilotinib, pazopanib, sorafenib, or sunitinib between January 1, 2008, and May 31, 2010. Coprescribing was 1 or more overlapping days of supply between the OAD and potential DDI drugs during the 12-month period beginning on the OAD index date. Product labels identified the cytochrome P450 metabolic enzymes used and whether P-glycoprotein was used by the OADs. Drugs that induce and/or inhibit these pathways were identified from the label and online resources.

Results: Sample sizes ranged from 96 (pazopanib group) to 4617 (imatinib group). Coprescribing rates with drugs that may decrease OAD effectiveness were 359/1546 (23%) (sunitinib group) to 1851/3263 (57%) (erlotinib group). Coprescribing rates with drugs that may increase OAD toxicity were 364/1546 (24%) (sunitinib group) to 71/96 (74%) (pazopanib group). Patients coprescribed DDI drugs had a median of 1 to 4 more medications present on the OAD index date than those not coprescribed a DDI drug. Most groups coprescribed DDI drugs had a median of 180 or more OAD days of supply during follow-up. The proportion of OAD days of supply with overlapping days of DDI drugs ranged from 7% to 85%. Generally, oncologists prescribed the OAD and nononcologists the DDI drug.

Conclusion: Coprescription of drugs that induce or inhibit metabolic pathways used by enzyme-targeted kinase inhibitor OADs is high. The clinical consequences need further study.