Coadministration with acid-reducing agents (ARAs), including proton pump inhibitors (PPIs), histamine H₂-receptor antagonists (H₂ blockers), and antacids has been demonstrated to reduce antiviral exposure and efficacy. Therefore, it is essential that US Food and Drug Administration (FDA) drug labels include recommendations to manage these drug–drug interactions (DDIs). This investigation analyzed information in FDA drug labels to manage DDIs between ARAs and antivirals approved from 1998 to 2019. To ascertain clinical adoption, we assessed whether FDA label recommendations were incorporated into current antiviral clinical practice guidelines. We identified 82 label recommendations for 43 antiviral approvals. Overall, 56.1% of recommendations were deemed clinically actionable, with the most common actionable management strategies being dose adjustment during coadministration (40.2%) and coadministration not recommended (9.8%). The sources informing DDI recommendations were clinical DDI studies (59.8%) and predictions of altered exposure (40.2%). Antivirals with low aqueous solubility were more likely to have label recommendations and were more commonly investigated using clinical DDI studies (P < 0.01). For recommendations informed by clinical DDI studies, changes in drug exposure were associated with actionable label recommendations (P < 0.01). The frequency of exposure changes in clinical DDI studies was similar across antiviral indications, but exposure changes were numerically higher for antacids (71.4%) relative to PPIs (42.9%) and H₂ blockers (28.6%). Of DDI pairs identified within drug labels, 76.8% were included in guidelines, and recommended management strategies were concordant in 90.5% of cases. Our findings demonstrate that current regulatory oversight mostly (but not completely) results in actionable label recommendations to manage DDIs for high-risk antivirals.

中文翻译：

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美国食品和药物管理局药物标签建议抗病毒药和酸还原剂联合用药的评估

与减酸剂 (ARAs) 共同给药，包括质子泵抑制剂 (PPIs)、组胺 H ₂ -受体拮抗剂 (H ₂阻滞剂）和抗酸剂已被证明可以减少抗病毒药物的暴露和疗效。因此，美国食品和药物管理局 (FDA) 的药物标签必须包含管理这些药物相互作用 (DDI) 的建议。该调查分析了 FDA 药物标签中的信息，以管理 1998 年至 2019 年批准的 ARA 和抗病毒药物之间的 DDI。为确定临床采用情况，我们评估了 FDA 标签建议是否已纳入当前的抗病毒临床实践指南。我们为 43 种抗病毒药物批准确定了 82 项标签建议。总体而言，56.1% 的建议被认为在临床上是可行的，最常见的可行管理策略是在共同给药期间调整剂量 (40.2%) 和不推荐共同给药 (9.8%)。提供 DDI 建议的来源是临床 DDI 研究 (59.8%) 和暴露改变的预测 (40.2%)。水溶性低的抗病毒药物更可能有标签推荐，并且更常使用临床 DDI 研究进行研究（P  < 0.01）。对于临床 DDI 研究提供的建议，药物暴露的变化与可操作的标签建议相关（P  < 0.01）。临床 DDI 研究中暴露变化的频率在抗病毒适应症中相似，但抗酸剂 (71.4%) 的暴露变化在数值上高于 PPI (42.9%) 和 H 2_阻滞剂(28.6%)。在药物标签中确定的 DDI 对中，76.8% 包含在指南中，推荐的管理策略在 90.5% 的案例中是一致的。我们的研究结果表明，当前的监管监督主要（但不完全）会产生可操作的标签建议，以管理高风险抗病毒药物的 DDI。