Table 1.
Select Classes of Drugs and Their Reported Cardiotoxicities in Drug Labels
| Class of Anticancer Drug | Example | Initial FDA Approval∗ | Boxed Warning∗ | W and P Label∗ |
|---|---|---|---|---|
| Alkylating agents | Cyclophosphamide | 1959 | Myocarditis, pericarditis, pericardial effusion, arrhythmias, and CHF | |
| Antimetabolites | 5-fluorouracil (5-FU) | 1962 | Myocardial ischemia, angina | |
| Anthracyclines | Doxorubicin | 1974 | CHF | Arrhythmia |
| Liposomal doxorubicin | 1995 | CHF | ||
| Epirubicin | 1999 | CHF | Arrhythmia, thrombophlebitis | |
| Taxanes | Paclitaxel | 1992 | Severe conduction abnormalities, hypotension, bradycardia, and HTN | |
| HER2 inhibitors | Trastuzumab | 1998 | CHF | Cardiac dysfunction, arrhythmia, HTN |
| Pertuzumab | 2012 | Cardiac dysfunction | ||
| Ado-trastuzumab emtansine | 2013 | LV dysfunction | ||
| Tyrosine kinase inhibitors (TKIs) | Imatinib | 2001 | Edema, CHF, hypereosinophilic cardiac toxicity | |
| Dasatinib | 2006 | Cardiac dysfunction, PAH, QT prolongation, fluid retention including pleural and pericardial effusion | ||
| Nilotinib | 2007 | QT prolongation, torsades de pointes, sudden death | Ventricular repolarization abnormalities, cardiac and arterial vascular occlusive events, fluid retention including pleural and pericardial effusion | |
| Crizotinib | 2011 | Bradycardia, QT prolongation | ||
| Ponatinib | 2012 | Arterial thrombosis (fatal MI, stroke) | CHF, HTN, fluid retention, arrhythmia | |
| Cabozantinib | 2012 | Severe hemorrhage | Arterial thromboembolic events (MI, stroke), HTN | |
| Ibrutinib | 2013 | Atrial fibrillation | ||
| VEGF signaling pathway inhibitors | Bevacizumab | 2004 | Severe hemorrhage | MI, stroke, DVT, HTN |
| Sorafenib | 2005 | Ischemia, QT prolongation, HTN | ||
| Sunitinib | 2006 | Ischemia, CHF, QT prolongation, torsades de pointes, HTN | ||
| Pazopanib | 2009 | QT prolongation, torsades de pointes, cardiac dysfunction, HTN, arterial and venous thrombotic events | ||
| Vandetanib | 2011 | QT prolongation, torsades de pointes, sudden deaths | Ischemic cerebrovascular events, hemorrhage, heart failure, HTN | |
| Axitinib | 2012 | HTN, arterial and venous thrombotic events, hemorrhagic events | ||
| Regorafenib | 2012 | Myocardial ischemia, HTN, hemorrhagic events | ||
| mTOR inhibitors | Temsirolimus | 2007 | Hyperglycemia, hyperlipidemia | |
| Everolimus | 2009 | Hyperglycemia, hyperlipidemia, hypertriglyceridemia | ||
| Immunomodulators | Thalidomide | 1998 | DVT, PE | MI, stroke, bradycardia |
| Lenalidomide | 2005 | DVT, PE | ||
| Pomalidomide | 2013 | DVT, PE | ||
| Proteasome inhibitors (PIs) | Bortezomib | 2003 | Hypotension, heart failure, few cases of PAH | |
| Carfilzomib | 2012 | Heart failure, myocardial ischemia, PAH, HTN, venous thrombotic events | ||
| Cancer immunotherapies | Ipilimuab | 2011 | <1% Pericarditis and myocarditis | |
| Nivolumab | 2014 | |||
| Pembrolizumab | 2014 |
CHF = congestive heart failure; DVT = deep vein thrombosis; FDA = Food and Drug Administration; HTN = hypertension; MI = myocardial infarction; NA = not applicable; PAH = pulmonary hypertension; PE = pulmonary embolism; W and P = warnings and precautions.
Data from the U.S. FDA (100). Both boxed warnings and W and P sections of labeling for human prescription drugs are recommended by the FDA as industry guidance to categorize reporting of various adverse reactions. The boxed warnings highlight serious cardiotoxicities (fatal, life-threatening, or permanently disabling), adverse reactions that can be prevented or alleviated, or use with safety restrictions. In addition to the boxed warning, the W and P section describes a discrete set of cardiovascular adverse reactions that are serious or are otherwise clinically significant because they have implications for prescribing decisions or for patient management.