title: Prescription behavior for gastroprotective drugs in new users as a result of communications regarding clopidogrel - proton pump inhibitor interaction.
abstract: Safety concerns of the concomitant use of clopidogrel and proton pump inhibitors (PPIs) were published in 2009 and 2010 by the medicines regulatory agencies, including a direct healthcare professional communication. We examined the association between various safety statements and prescription behavior for gastroprotective drugs in naïve patients in the Netherlands during the years 2008-2011. Data from the PHARMO Database Network were analyzed with interrupted time series analyses to estimate the impact of each communication on drug prescriptions. Dispensings were used as a proxy variable for prescription behavior. After the early communication in January 2009, 15.5% (95% CI 7.8, 23.4) more patients started concomitantly with (es)omeprazole and 13.8% (95% CI 6.5, 21.2) less with other PPIs. Directly after the first statement in June 2009, we found a steep increase in histamine 2-receptor antagonists (H2RA) peaking at 25%, placing those patients at risk for gastrointestinal events. This effect for H2RA faded away after a few months. In February 2010, when the official advice via an adjusted statement was to avoid (es)omeprazole, we found a decrease of 11.9% (95% CI 5.7, 18.2) for (es)omeprazole and an increase of +16.0% (95% CI 10.3, 21.7) for other PPIs. Still 22.6% (95% CI 19.5, 25.7) of patients started on (es)omeprazole in February 2010, placing them at risk for cardiovascular events. Advices of regulatory authorities were followed, however, reluctantly and not fully, probably partly because of the existing scientific doubt about the interaction.
authors.affiliation: Department of Clinical Pharmacy Medisch Spectrum Twente Enschede The Netherlands; Present address: Department of Clinical Pharmacy Saxenburgh Group Hardenberg The Netherlands.
authors.forename: Willemien J
authors.initials: WJ
authors.lastname: Kruik-Kollöffel
authors.affiliation: Medical School Twente Medisch Spectrum Twente Enschede The Netherlands; Department of Research Methodology, Measurement and Data Analysis University of Twente Enschede The Netherlands.
authors.forename: Job
authors.initials: J
authors.lastname: van der Palen
authors.affiliation: Department of Cardiology Hospital Group Twente Almelo and Hengelo The Netherlands.
authors.forename: H Joost
authors.initials: HJ
authors.lastname: Kruik
authors.affiliation: Pharmo Institute Utrecht The Netherlands.
authors.forename: Myrthe P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.affiliation: Department of Clinical Pharmacy Medisch Spectrum Twente Enschede The Netherlands.
authors.forename: Kris L L
authors.initials: KL
authors.lastname: Movig
keywords: Antiulcer agents; clopidogrel; drug interactions; drug safety; histamine H2 antagonists; pharmacoepidemiology; pharmacovigilance; proton pump inhibitors; risk assessment; risk factors