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Direct oral anticoagulants have become increasingly used for atrial fibrillation and venothromboembolic disease. Thus far, there have been a few published cases of pericardial effusion associated with rivaroxban. However, there has been little published regarding the effects of concurrent medications and their effect on the cytochrome enzyme systems involved in rivaroxaban metabolism. We present a case of a 76-year-old female who develops a spontaneous haemopericardium after initiating rivaroxaban. After thorough medical reconciliation, we offer pharmacokinetic mechanisms that may have contributed to the haemopericardium. This case demonstrates the importance of reviewing patients medication lists and utilizing basic pharmacokinetics to prevent adverse events.