Faculty of Health Sciences, Oslo Metropolitan University, P.O. Box 4 St. Olavs plass, N-0130, Oslo, Norway.
Department of Clinical Pharmacology, St. Olav's University Hospital, Trondheim, Norway.
Eur J Clin Pharmacol. 2022 Oct;78(10):1623-1632. doi: 10.1007/s00228-022-03364-5. Epub 2022 Jul 25.
To compare the co-prescription of metoprolol and potent CYP2D6-inhibiting antidepressants before and during a 10-year period after implementation of an optimized drug interaction database into clinical decision support systems in Norway.
The study was a retrospective, cross-sequential nationwide analysis of drug-dispensing data retrieved from the Norwegian Prescription Database over a 1-year period before (2007) and two 1-year periods after (2012 and 2017) implementation of a drug interaction database providing recommendations on non-interacting alternative medications. Primary outcome was changes in co-prescription rates of metoprolol and the potent CYP2D6-inhibiting antidepressants fluoxetine, paroxetine, or bupropion relative to alternative antidepressants with no or limited CYP2D6 inhibitory potential. To control for potential secular trend bias, a comparison group consisting of atenolol/bisoprolol users was included.
The co-prescription rate of metoprolol with potent CYP2D6 inhibitors declined following implementation of the optimized database, by 21% (P < 0.001) after 5 years and by 40% (P < 0.001) after 10 years. Compared with atenolol/bisoprolol users, patients treated with metoprolol had significantly reduced likelihood of being prescribed a CYP2D6-inhibiting antidepressant in the two post-implementation periods (OR 0.61 (95% CI 0.54-0.69) and OR 0.45 (95% CI 0.40-0.51), respectively, versus OR 0.84 (95% CI 0.74-0.94) prior to implementation). Small and mostly insignificant differences in average daily metoprolol dosage were found between patients treated with the various antidepressants.
The present study suggests that implementation of a drug interaction database providing recommendations on non-interacting drug alternatives contributes to reduced co-prescribing of drug combinations associated with potentially serious adverse effects.
比较在挪威将优化后的药物相互作用数据库纳入临床决策支持系统前后的 10 年期间，美托洛尔与强效 CYP2D6 抑制性抗抑郁药联合处方的情况。
这是一项回顾性、交叉性全国性药物配药数据分析研究，数据来自挪威处方数据库，时间跨度为实施药物相互作用数据库前的 1 年（2007 年）、实施后 2 年（2012 年和 2017 年），该数据库提供关于非相互作用替代药物的建议。主要结局指标是美托洛尔与氟西汀、帕罗西汀或安非他酮等强效 CYP2D6 抑制剂联合处方的比例相对于无或有限 CYP2D6 抑制潜力的替代抗抑郁药的变化。为了控制潜在的季节性趋势偏差，纳入了阿替洛尔/比索洛尔使用者作为对照组。
实施优化数据库后，美托洛尔与强效 CYP2D6 抑制剂联合处方的比例下降，5 年后下降 21%（P<0.001），10 年后下降 40%（P<0.001）。与阿替洛尔/比索洛尔使用者相比，接受美托洛尔治疗的患者在实施后的两个时期，被开处方使用 CYP2D6 抑制剂抗抑郁药的可能性显著降低（OR 0.61（95%CI 0.54-0.69）和 OR 0.45（95%CI 0.40-0.51），而实施前为 OR 0.84（95%CI 0.74-0.94））。接受各种抗抑郁药治疗的患者之间，美托洛尔的平均日剂量差异较小且大多无统计学意义。
本研究表明，实施提供非相互作用药物替代方案建议的药物相互作用数据库有助于减少与潜在严重不良反应相关的药物联合处方。
