Interactions between cardiology and oncology drugs in precision cardio-oncology

Abstract

Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.

Keywords: Cardio-Oncology; Drug Interactions; cancer; cardiovascular disease; cyp450; p-glycoprotein.

Figure 1.

Sample substrates, inhibitors, and inducers of CYP450 and P-g in Cardio-Oncology

Figure 2.. Example case of a patient on ibrutinib who develops atrial fibrillation and is initiated on low-dose apixaban

Moderate potential drug interaction between ibrutinib and Factor Xa inhibitors (e.g., apixaban, rivaroxaban, edoxaban) is mediated by P-g (ibrutinib is an inhibitor of P-g), and both ibrutinib and Factor Xa inhibitors are substrates of P-g and cytochrome protein 450 3A4 (CYP3A4). When ibrutinib is used concurrently, the dose of Factor Xa inhibitors should be reduced (supported by expert opinion [9,13] and recommendations/guidelines [14]) (e.g., apixaban dose reduced to 2.5 mg twice daily compared with the usual 5 mg twice daily). Concurrent use of direct thrombin inhibitors (e.g., dabigatran not illustrated here) should be avoided due to a major drug interaction mediated by P-g (ibrutinib is an inhibitor of P-g). Stock photo not of actual patient.

Figure 3.. The modified P*3 pathway for clinical implementation of precision cardiovascular medicine

Used with permission [5], adapted from [121].