Teva Pharmaceutical Industries Ltd, Petach Tikva, Israel.
IQVIA (formerly IMS Health), Munich, Germany.
Curr Med Res Opin. 2019 Jan;35(1):33-40. doi: 10.1080/03007995.2018.1499507. Epub 2018 Aug 21.
In response to safety concerns, risk minimization measures (RMM) for flupirtine were implemented in Europe in 2013 to reduce hepatotoxicity risk. This study aims to characterize compliance and prescribing practices of flupirtine before and after RMM implementation. A retrospective pre-post design cohort study was conducted in the outpatient setting using a longitudinal electronic medical record database in Germany. The study population included patients who initiated flupirtine. One-year pre- and post-implementation periods were assessed. Six RMM elements were evaluated, including indication of acute pain, use for maximum of 2 weeks, use when other analgesics are contraindicated, no pre-existing liver disease or alcohol abuse, no concomitant drug induced liver injury, and weekly liver function tests. The number of flupirtine users decreased by 34.4% from 18,291 in the pre-implementation period (2012) to 12,000 in the post-implementation period (April 2015 to March 2016). Elements of RMM with substantial improvement included flupirtine prescription duration, where the proportion of patients with duration ≤14 days increased significantly by 16.5% from 74.8% to 91.3% in the pre- and post-implementation periods, respectively. RMM with a moderate-to-high degree of compliance during the post-implementation period, although with a very small or no change from the pre- implementation period, included restriction of flupirtine prescribing to patients with acute pain when other analgesics are contraindicated, and avoiding use in patients with either pre-existing liver disease or concomitant drugs known to have a potential hepatotoxic effect. Weekly liver function tests had a low degree of compliance. These findings demonstrate that, while physicians restricted flupirtine prescriptions to short-term use in the target population of acute pain, not all drug labeling elements were followed to the same extent in routine practice.
针对安全性问题，欧洲于 2013 年实施了氟比洛芬的风险最小化措施（RMM），以降低肝毒性风险。本研究旨在描述 RMM 实施前后氟比洛芬的使用情况和处方实践。这是一项在德国门诊环境下进行的回顾性前后设计队列研究，使用纵向电子病历数据库。研究人群包括开始使用氟比洛芬的患者。评估了实施前后各 1 年的情况。评估了 6 个 RMM 要素，包括急性疼痛的适应证、最长使用 2 周、其他镇痛药禁忌时使用、无预先存在的肝病或酒精滥用、无伴随的药物性肝损伤、以及每周肝功能检查。氟比洛芬的使用者数量从实施前的 18291 人减少到实施后的 12000 人，减少了 34.4%。RMM 要素中，氟比洛芬的处方持续时间有了显著改善，在实施前后的比例分别从 74.8%增加到 91.3%，有 16.5%的患者持续时间≤14 天。在实施期间，尽管从实施前到实施后仅有很小或没有变化，但仍有一定程度的符合 RMM 要求的要素，包括限制氟比洛芬仅用于其他镇痛药禁忌的急性疼痛患者，避免在有预先存在的肝病或已知有潜在肝毒性的伴随药物的患者中使用。每周肝功能检查的符合率较低。这些发现表明，尽管医生将氟比洛芬的处方限制在急性疼痛的目标人群中短期使用，但并非所有药物标签要素在常规实践中都得到了同等程度的遵循。
