San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
Ann Pharmacother. 2010 Jan;44(1):28-34. doi: 10.1345/aph.1M475. Epub 2009 Dec 29.
Black box warnings represent the strongest safety warning that the Food and Drug Administration can issue for a marketed prescription drug. Some black box warnings recommend against coadministration of specific medications due to an increased risk for serious, perhaps life-threatening, effects.
To determine the level of agreement in presence, clinical severity scores level of documentation ratings, and alert content among 3 leading drug interaction screening programs with regard to contraindicated comedications that are mentioned in black box warnings.
We reviewed the prescribing information for currently marketed prescription drugs with a black box warning that mentioned a contraindicated drug combination. We selected the drug interaction databases Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Comp Lexi-Interact to evaluate the interactions. Discrepancies in the inclusion of interactions and level of agreement in clinical severity scores and level of documentation ratings for each interaction were assessed, using descriptive statistics, Spearman's correlation coefficient, Kendall-Stuart tau-c, and Cronbach's alpha.
We identified 11 drugs with black box warnings that contained information on 59 unique contraindicated drug combinations, only 68% of which were covered by any source. Lexi-Comp detected the most interactions (n = 29) and DRUG-REAX the least (n = 18). Only 3 drug combinations were detected and rated as contraindicated or potentially life-threatening in all 3 databases. The severity scores and level of documentation ratings varied widely.
There are discrepancies among major drug interaction screening programs in the inclusion, severity, and level of documentation of contraindicated drug combinations mentioned in black box warnings. Further studies could explore the implications of these inconsistencies, particularly with regard to the integration of black box warning information in clinical practice. Clinicians should consult multiple drug resources to maximize the potential for detecting a potentially severe drug interaction.
黑框警告代表了美国食品和药物管理局（FDA）对已上市处方药发出的最强安全警告。一些黑框警告建议避免联合使用特定药物，因为这会增加严重的、可能危及生命的影响风险。
确定 3 个主要药物相互作用筛选程序在存在、临床严重程度评分级别、文档记录评级和警示内容方面对黑框警告中提到的禁忌药物组合的一致性水平。
我们审查了目前市场上有黑框警告的处方药的处方信息，这些警告提到了禁忌药物组合。我们选择了 Facts & Comparisons 4.0、MICROMEDEX DRUG-REAX 和 Lexi-Comp Lexi-Interact 等药物相互作用数据库来评估这些相互作用。使用描述性统计、Spearman 相关系数、Kendall-Stuart tau-c 和 Cronbach's alpha 评估每个相互作用的纳入差异和临床严重程度评分以及文档记录评级的一致性水平。
我们确定了 11 种带有黑框警告的药物，其中包含了 59 种独特的禁忌药物组合的信息，只有 68%的信息被任何来源涵盖。Lexi-Comp 检测到的相互作用最多（n=29），而 DRUG-REAX 检测到的最少（n=18）。只有 3 种药物组合在所有 3 个数据库中被检测到并被评为禁忌或潜在危及生命。严重程度评分和文档记录评级差异很大。
在纳入、严重程度和文档记录评级方面，主要药物相互作用筛选程序存在差异，这些差异涉及黑框警告中提到的禁忌药物组合。进一步的研究可以探讨这些不一致性的影响，特别是在将黑框警告信息整合到临床实践中的问题。临床医生应咨询多种药物资源，以最大限度地提高发现潜在严重药物相互作用的可能性。
