Camille Morival1,2,3,4, Richard Westerlynck2,3,5,6, Guillaume Bouzillé2,3,5, Marc Cuggia2,3,5, Pascal Le Corre7,8. 1. CHU Rennes, Pôle Pharmacie, Service Hospitalo-Universitaire de Pharmacie, 35033, Rennes Cedex, France. 2. CHU Rennes, CIC Inserm 1414, 35000, Rennes, France. 3. Université de Rennes 1, LTSI, Inserm U1099, 35000, Rennes, France. 4. Laboratoire de Pharmacie Galénique, Laboratoire de Biopharmacie et Pharmacie Clinique, IRSET U1085, Faculté de Pharmacie, Université de Rennes 1, 35043, Rennes Cedex, France. 5. CHU Rennes, Centre de Données Cliniques, 35000, Rennes, France. 6. Ecole nationale de la statistique et de l'analyse de l'information, 35000, Rennes, France. 7. CHU Rennes, Pôle Pharmacie, Service Hospitalo-Universitaire de Pharmacie, 35033, Rennes Cedex, France. pascal.le-corre@univ-rennes1.fr. 8. Laboratoire de Pharmacie Galénique, Laboratoire de Biopharmacie et Pharmacie Clinique, IRSET U1085, Faculté de Pharmacie, Université de Rennes 1, 35043, Rennes Cedex, France. pascal.le-corre@univ-rennes1.fr.
Abstract
AIM: Our aim was to describe prevalence, nature, and level of severity of potential statin drug-drug interactions in a university hospital. METHODS: In a cross-sectional study, statin drug-drug interactions were screened from medical record of 10,506 in-patients treated stored in the clinical data warehouse "eHOP." We screened drug-drug interactions using Theriaque and Micromedex drug databases. RESULTS: A total of 22.5% of patients were exposed to at least one statin drug-drug interaction. Given their lipophilicity and CYP3A4 metabolic pathway, atorvastatin and simvastatin presented a higher prevalence of drug-drug interactions while fluvastatin presented the lowest prevalence. Up to 1% of the patients was exposed to a contraindicated drug-drug interaction, the most frequent drug-drug interaction involving influx-transporter (i.e., OATP1B1) interactions between simvastatin or rosuvastatin with cyclosporin. The second most frequent contraindicated drug-drug interaction involved CYP3A4 interaction between atorvastatin or simvastatin with either posaconazole or erythromycin. Furthermore, our analysis showed some discrepancies between Theriaque and Micromedex in the prevalence and the nature of drug-drug interactions. CONCLUSIONS: Different drug-drug interaction profiles were observed between statins with a higher prevalence of CYP3A4-based interactions for lipophilic statins. Analyzing the three most frequent DDIs, the more significant DDIs (level 1: contraindication) were reported for transporter-based DDI involving OATP1B1 influx transporter. These points are of concern to improve prescriptions of statins.
AIM: Our aim was to describe prevalence, nature, and level of severity of potential statin drug-drug interactions in a university hospital. METHODS: In a cross-sectional study, statin drug-drug interactions were screened from medical record of 10,506 in-patients treated stored in the clinical data warehouse "eHOP." We screened drug-drug interactions using Theriaque and Micromedex drug databases. RESULTS: A total of 22.5% of patients were exposed to at least one statin drug-drug interaction. Given their lipophilicity and CYP3A4 metabolic pathway, atorvastatin and simvastatin presented a higher prevalence of drug-drug interactions while fluvastatin presented the lowest prevalence. Up to 1% of the patients was exposed to a contraindicated drug-drug interaction, the most frequent drug-drug interaction involving influx-transporter (i.e., OATP1B1) interactions between simvastatin or rosuvastatin with cyclosporin. The second most frequent contraindicated drug-drug interaction involved CYP3A4 interaction between atorvastatin or simvastatin with either posaconazole or erythromycin. Furthermore, our analysis showed some discrepancies between Theriaque and Micromedex in the prevalence and the nature of drug-drug interactions. CONCLUSIONS: Different drug-drug interaction profiles were observed between statins with a higher prevalence of CYP3A4-based interactions for lipophilic statins. Analyzing the three most frequent DDIs, the more significant DDIs (level 1: contraindication) were reported for transporter-based DDI involving OATP1B1 influx transporter. These points are of concern to improve prescriptions of statins.
Entities:
Keywords:
Clinical data warehouse; Data mining; Drug databases; Drug transporters; Drug-drug interactions; Metabolic enzymes; Pharmacokinetics; Statins
Authors: Jacob Abarca; Daniel C Malone; Edward P Armstrong; Amy J Grizzle; Philip D Hansten; Robin C Van Bergen; Richard B Lipton Journal: J Am Pharm Assoc (2003) Date: 2004 Mar-Apr
Authors: Richard T Scheife; Lisa E Hines; Richard D Boyce; Sophie P Chung; Jeremiah D Momper; Christine D Sommer; Darrell R Abernethy; John R Horn; Stephen J Sklar; Samantha K Wong; Gretchen Jones; Mary L Brown; Amy J Grizzle; Susan Comes; Tricia Lee Wilkins; Clarissa Borst; Michael A Wittie; Daniel C Malone Journal: Drug Saf Date: 2015-02 Impact factor: 5.606