Azacitidine-Induced Pericarditis: A Case Series

Abstract

Azacitidine is a DNA methyltransferase inhibitor approved by the United States Food and Drug Administration for the treatment of myelodysplastic syndromes, and used off-label for the treatment of acute myeloid leukemia and chronic myelomonocytic leukemia.Azacitidine is cytotoxic at high doses, whereas at lower doses, it induces DNA demethylation and differentiation. Commonly reported adverse effects include cytopenias, gastrointestinal symptoms such as nausea and vomiting, and injection-site erythema. To our knowledge, no reports of pericarditis secondary to azacitidine have been published. We describe three cases of pericarditis possibly related to azacitidine administration in a span of 3 years at our center. Patient no. 1 presented with pericarditis after cycle 2 of azacitidine, patient no. 3 presented 3 weeks after completing cycle 5, and patient no. 2 presented during cycle 1 and had prior history of pericarditis, although she was completely asymptomatic at the start of treatment. In addition, transthoracic echocardiography in patient no. 1 was within normal limits whereas that of patient nos. 2 and 3 showed a new pericardial effusion. The onset of symptoms with repeated administration may suggest that cardiotoxicity could be secondary to a hypersensitivity or immune reaction. This would be also supported by the quick resolution of symptoms with corticosteroid therapy in the three patients. Use of the Naranjo adverse drug reaction probability scale indicated a probable adverse drug reaction (score of 6) for patient nos. 1 and 3 and a possible adverse drug reaction (score of 3) for patient no. 2. With the exclusion of other common causes of pericarditis, we believe it is likely that azacitidine was responsible for the findings in our patients. Providers caring for patients receiving hypomethylating agents should consider this potential adverse drug reaction in the setting of unexplained chest pain or other clinical signs consistent with cardiotoxicity. We encourage providers to report similar and new adverse drug reactions to the United States Food and Drug Administration, as we did through their MedWatch program, or their appropriate local agencies.

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