Rocour Samuel, Cochard Baptiste, Daniel Valérie, Martin Ludovic, Corvaisier Mathieu
Department of Dermatology, University Hospital of Angers, Angers, France.
Department of Pharmacy, University Hospital of Angers, Angers, France.
J Clin Pharmacol. 2023 Jan;63(1):29-39. doi: 10.1002/jcph.2125. Epub 2022 Aug 10.
C1-inhibitor (C1INH) concentrates and the selective bradykinin B2 receptor antagonist icatibant are approved only for treating hereditary angioedema with C1INH deficiency. Yet, they are regularly prescribed off label in other types of bradykinin-mediated angioedema including angiotensin-converting enzyme inhibitor (ACEi)-related and undetermined angioedema. We conducted a retrospective chart review of inpatient prescriptions of C1INH concentrates and icatibant between 2016 and 2020 in the University Hospital of Angers. The first outcome was the proportion of prescriptions with explicit indication. Then, we determined the compliance of prescriptions with European Medicines Agency approvals and the French bradykinin-mediated angioedema reference center guidelines. Finally, we estimated the economic impact of inappropriate prescribing. The therapeutic indication was explicit in 90.4% of prescriptions (n = 66/73). Only 17.8% of prescriptions were for hereditary angioedema with C1INH deficiency, while 31.5% were for ACEi-related and 28.7% for undetermined angioedema. However, most off-label prescriptions were consistent with the French bradykinin-mediated angioedema reference center guidelines (73.3%). We estimated that 13% of drug expenditures were potentially excessive. The predominance of off-label prescriptions may be explained by the infrequency of hereditary angioedema and the absence of approved alternatives in other types of bradykinin-mediated angioedema. Most attacks were related to ACEis. Epinephrine was rarely prescribed as first-line therapy in attacks of unknown origin. Given the high prices of these drugs, we advocate the development of a readily available management algorithm of angioedema to reduce inappropriate prescriptions in our center. In addition, we think that the drug prescription circuit should be redesigned to ensure the traceability of prescribed vials in the dispensing areas.
C1抑制剂（C1INH）浓缩物和选择性缓激肽B2受体拮抗剂艾替班特仅被批准用于治疗伴有C1INH缺乏的遗传性血管性水肿。然而，它们经常被超适应症处方用于其他类型的缓激肽介导的血管性水肿，包括与血管紧张素转换酶抑制剂（ACEi）相关的血管性水肿和不明原因的血管性水肿。我们对2016年至2020年期间昂热大学医院住院患者使用C1INH浓缩物和艾替班特的处方进行了回顾性图表审查。首要结果是有明确适应症的处方比例。然后，我们确定了处方是否符合欧洲药品管理局的批准以及法国缓激肽介导的血管性水肿参考中心的指南。最后，我们估计了不适当处方的经济影响。90.4%的处方（n = 66/73）有明确的治疗适应症。只有17.8%的处方用于伴有C1INH缺乏的遗传性血管性水肿，而31.5%用于与ACEi相关的血管性水肿，28.7%用于不明原因的血管性水肿。然而，大多数超适应症处方符合法国缓激肽介导的血管性水肿参考中心的指南（73.3%）。我们估计13%的药物支出可能是过度的。超适应症处方占主导可能是由于遗传性血管性水肿发病率低以及其他类型的缓激肽介导的血管性水肿缺乏批准的替代药物。大多数发作与ACEi有关。在不明原因发作时，肾上腺素很少被用作一线治疗药物。鉴于这些药物价格高昂，我们主张制定一种易于获得的血管性水肿管理算法，以减少我们中心的不适当处方。此外，我们认为药品处方流程应重新设计，以确保配药区域所配药瓶的可追溯性。
