Létinier Louis, Ferreira Amandine, Marceron Alexandre, Babin Marina, Micallef Joëlle, Miremont-Salamé Ghada, Pariente Antoine
Univ. Bordeaux, INSERM, BPH, U1219, Team Pharmacoepidemiology, Bordeaux, France.
CHU de Bordeaux, Pole de Santé Publique, Service de Pharmacologie Médicale, Centre de Pharmacovigilance de Bordeaux, Bordeaux, France.
Front Pharmacol. 2021 Mar 24;11:624562. doi: 10.3389/fphar.2020.624562. eCollection 2020.
Few data are available on the clinical impact of drug-drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients' characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63-84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the "antithrombotic agents" subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs.
关于药物相互作用（DDIs）的临床影响，可用数据较少。大多数研究仅限于分析潜在药物相互作用的暴露情况，或少数几种药物或治疗类别联合使用的靶向影响。药物不良反应（ADR）报告分析可能是一种用于总体研究药物相互作用所致不良反应的方法。我们的目的是描述向法国药物警戒系统报告的由药物相互作用导致的药物不良反应的特征，并确定这些药物不良反应中最常涉及的药物。考虑2012年1月1日至2016年12月31日期间的所有药物不良反应报告，我们确定了所有由药物相互作用导致的药物不良反应病例（药物相互作用导致的药物不良反应）。然后，我们根据患者特征、药物不良反应的严重程度、涉及的药物（每个病例两种或更多）以及药物不良反应类型对这些病例进行了描述。在4027份与药物相互作用导致的药物不良反应相关的报告中，3303份与严重药物不良反应相关。发生严重药物相互作用导致的药物不良反应的患者中位年龄为76岁（四分位间距：63 - 84岁）；53%为男性。在所有严重药物相互作用导致的药物不良反应中，11%危及生命，8%致命。在36%的病例中，导致药物不良反应的药物相互作用涉及至少三种药物。总体而言，在考虑的3303份严重药物相互作用导致的药物不良反应报告中提到了8,424种不同的药物。总共，“抗血栓药物”亚组的药物在34%的严重药物相互作用导致的药物不良反应中被认定有罪。抗抑郁药是第二大最具代表性的治疗/药理亚组（占严重药物相互作用导致的药物不良反应的5%）。在考虑的3303份严重药物相互作用导致的药物不良反应报告中报告的3843种药物不良反应类型中，最常见的是出血（40%为临床出血；6%为生物学出血）、肾衰竭（8%）、药代动力学改变（5%）和心律失常（4%）。出血性事故仍然是法国报告中由药物相互作用导致的严重药物不良反应的重要组成部分。药物相互作用的其他临床后果似乎在药物警戒中识别得较少。此外，超过三分之一的严重药物相互作用导致的药物不良反应涉及至少三种药物。
Zotero 插件