Cardiology, Medical Affairs, Bayer Brasil SA, Sao Paulo, Brazil.
Medical Information, Medical Affairs, Bayer Brasil SA, Sao Paulo, Brazil.
Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620936325. doi: 10.1177/1076029620936325.
Data on drug-drug interactions (DDI) of antineoplastic drugs with anticoagulants is scarce. We aim to evaluate factors associated with DDI of antineoplastic and supportive care drugs with anticoagulants resulting in modification of pharmacokinetics of these last mentioned. A literature review on DDI databases and summaries of products characteristics (SmPC) was done. Drug-drug interactions of 257 antineoplastic and supportive care drugs with direct oral anticoagulants (DOACs), warfarin, enoxaparin, or fondaparinux were categorized as no clinically significant expected DDI, potentially weak DDI, potentially clinically significant DDI, and recommendation against coadministration. Logistic regression models were performed to analyze the association between the dependent variable potentially clinically significant interaction/recommendation against coadministration and the mechanisms of DDI. Of the 1799 associations, 84.4% were absence of DDI, 3.6% potentially weak DDI, 10.2% potentially clinically relevant DDI, and 2.0% recommendation against coadministration. Warfarin has higher DDI potential than other anticoagulants. Enoxaparin and fondaparinux have fewer DDI than others. There was no difference between DOACs. Drug-drug interactions with apixaban and rivaroxaban was independently associated with the absence of CYP3A4 competition, P-glycoprotein inhibition, CYP3A4 induction, and drug class of tyrosine kinase inhibitors. Drug-drug interactions with dabigatran and edoxaban was associated with inhibition of P-glycoprotein and tyrosine kinase inhibitors. Warfarin, induction of CYP3A4, and inhibition of CYP2C9. Enoxaparin and fondaparinux, only tyrosine kinase inhibitors. Direct oral anticoagulants did not differ regarding DDI with antineoplastic agents. Warfarin presented more DDI than other anticoagulants. P-glycoprotein inhibition and CYP3A4 induction were independently associated with DDI of antineoplastic agents with DOACs.
抗肿瘤药物与抗凝剂的药物-药物相互作用（DDI）数据很少。我们旨在评估与抗凝剂相关的抗肿瘤和支持性治疗药物的 DDI 因素，这些相互作用会改变后者的药代动力学。对 DDI 数据库和产品特征摘要（SmPC）进行了文献复习。将 257 种抗肿瘤和支持性治疗药物与直接口服抗凝剂（DOAC）、华法林、依诺肝素或磺达肝素的 DDI 分为无临床显著预期 DDI、潜在弱 DDI、潜在临床显著 DDI 和不建议联合用药。进行逻辑回归模型分析潜在临床显著相互作用/不建议联合用药的因变量与 DDI 机制之间的关系。在 1799 种关联中，84.4%无 DDI，3.6%潜在弱 DDI，10.2%潜在临床相关 DDI，2.0%不建议联合用药。华法林比其他抗凝剂具有更高的 DDI 潜力。依诺肝素和磺达肝素的 DDI 比其他药物少。DOAC 之间没有差异。阿哌沙班和利伐沙班与 CYP3A4 竞争、P-糖蛋白抑制、CYP3A4 诱导和酪氨酸激酶抑制剂药物类别无关的 DDI 独立相关。达比加群和依度沙班与 P-糖蛋白抑制和酪氨酸激酶抑制剂相关的 DDI。华法林、CYP3A4 诱导和 CYP2C9 抑制。依诺肝素和磺达肝素，仅与酪氨酸激酶抑制剂相关。直接口服抗凝剂与抗肿瘤药物的 DDI 无差异。华法林比其他抗凝剂有更多的 DDI。P-糖蛋白抑制和 CYP3A4 诱导与 DOAC 与抗肿瘤药物的 DDI 独立相关。
