title: 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).
  
  
  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.
  
  
  CONCLUSIONS
  Coprescription of drugs that induce or inhibit metabolic pathways used by enzyme-targeted kinase inhibitor OADs is high. The clinical consequences need further study.
authors: Medco Research Institute LLC, Medco Health Solutions Inc, an Express Scripts Company, Bethesda, MD, USA. sjbowlin1@gmail.com
authors: Steven J
authors: SJ
authors: Bowlin
authors: Fang
authors: F
authors: Xia
authors: Wenyi
authors: W
authors: Wang
authors: Keisha D
authors: KD
authors: Robinson
authors: Eric J
authors: EJ
authors: Stanek
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D062313:Databases, Pharmaceutical; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage; D014481:United States; D055815:Young Adult
chemical_list: D001549:Benzamides; D007191:Indazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D000068877:Imatinib Mesylate; D040262:Receptors, Vascular Endothelial Growth Factor