DataSheet1_Potentially Hazardous Drug-Drug Interactions Associated With Oral Antineoplastic Agents Prescribed in Chinese Tertiary Care Teaching Hospital Settings: A Multicenter Cross-Sectional Study.docx

Background: Oral administration increases the risk of interactions, because most oral antineoplastic agents (OAAs) are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Potential drug–drug interactions (DDIs) are commonly observed in patients with cancer, while the extent to which OAAs related hazardous DDIs remains unclear.Methods: We studied the contraindication patterns between oral antineoplastic agents and other medications among cancer patients in two tertiary care teaching hospitals in China. A total of 20 clinically significant hazardous DDI pairs that involved 30 OAAs were identified based on the predetermined criteria. Patient medications were checked for DDIs by using the US Food and Drug Administration approved labeling. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out.Results: In this study, 13,917 patients were included and a total of 297 DDIs were identified. The results revealed that proton pump inhibitors (PPIs), dexamethasone and fluoroquinolones were the most often involved hazardous DDIs with OAAs. The most prevalent contraindication is the simultaneous use of certain molecular targeted agents and PPIs. In the result of the multivariate analysis, younger age (0–20 group), increasing number of drugs and patient treated with targeted therapy had a higher risk for DDIs.Conclusion: The prevalence of OAAs related hazardous DDIs appears to be low in the cancer patients. However, physicians and clinical pharmacologists should be aware of the potential hazardous DDIs when prescribing OAAs, especially certain pH-dependent molecular targeted agents and potential QTc prolonging drugs.

背景：口服给药增加了药物相互作用的风险，因为大多数口服抗癌药物（OAAs）均为每日服用。药物相互作用可能增加抗肿瘤药物暴露或导致治疗失败。在癌症患者中，潜在的药物-药物相互作用（DDIs）普遍存在，而与OAAs相关的有害DDIs的程度尚不明确。方法：本研究在中国两家三级甲等教学医院中研究了口服抗癌药物与其他药物之间的禁忌症模式。根据预定的标准，确定了20对具有临床意义的危险DDI，涉及30种OAAs。通过使用美国食品药品监督管理局批准的标签对患者的药物进行检查以确定DDI。结果：本研究纳入了13,917名患者，共确定了297个DDI。结果显示，质子泵抑制剂（PPIs）、地塞米松和氟喹诺酮类是常与OAAs相关的危险DDIs。最常见的禁忌症是某些分子靶向药物与PPIs的联合使用。在多变量分析结果中，年轻年龄（0-20组）、药物数量增加以及接受靶向治疗的患者DDI风险较高。结论：与OAAs相关的有害DDIs在癌症患者中的发生率似乎较低。然而，医生和临床药理学家在开具OAAs处方时，应警惕潜在的DDIs，尤其是某些pH依赖性的分子靶向药物和可能延长QTc的药物。