‘Black box warning’ (BBW) labels for selected antiplatelet agents
| Drug | FDA initial approval | Date of BBW | Warning |
| Clopidogrel (Plavix) | November 17, 1997 | March 12, 2010 | The effectiveness of clopidogrel results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP-450) system, principally CYP2C19. Clopidogrel at recommended doses forms less of the active metabolite and has a reduced effect on platelet activity in patients who are homozygous for non-functional alleles of the CYP2C19 genes (termed ‘CYP2C19 poor metabolizers’). Tests are available to identify patients who are CYP2C19 poor metabolizers. Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers |
| Dipyridamole/ASA (Aggrenox) | November 22, 1999 | N/A | – |
| Eptifibatide (Integrilin) | June 8, 2001 | N/A | – |
| Prasugrel (Effient) | July 10, 2009 | July 10, 2009 | Prasugrel can cause significant and sometimes fatal bleeding. Do not use prasugrel in patients with active pathological bleeding or a history of transient ischemic attack or stroke. Risk factors for bleeding include bodyweight <60 kg, propensity to bleed, and concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic, chronic use of NSAIDs). Prasugrel is not recommended in patients 75 years of age or older, except for high-risk situations (diabetes, history of prior myocardial infarction). Do not start prasugrel in patients likely to undergo urgent CABG and discontinue at least 7 days before any surgery. If possible, manage bleeding without discontinuing prasugrel, as discontinuation in the first few weeks after acute coronary syndrome may increase risk for subsequent cardiovascular events |
| Ticagrelor (Brilinta) | July 20, 2011 | July 20, 2011 | Ticagrelor can cause significant, sometimes fatal, bleeding. Do not use in patients with active pathological bleeding or history of intracranial hemorrhage. Do not start in patients undergoing urgent CABG. If possible, manage bleeding without discontinuing ticagrelor. Stopping ticagrelor increases the risk of subsequent cardiovascular events. Maintenance doses of aspirin above 100 mg in patients with acute coronary syndrome reduce the effectiveness of ticagrelor and should be avoided |
Reference: https://www.fda.gov/drugs/drug-safety-and-availability/drug-safety-communications Accessed November 1, 2022.97
ASA, aspirin; CABG, coronary artery bypass grafting; FDA, US Food and Drug Administration; NSAIDs, non-steroidal anti-inflammatory drugs.