Torsades de pointes associated with methadone and voriconazole

This report concerns a case of torsades de pointes (TdP) associated with the concomitant administration of methadone and voriconazole in a patient with comorbid medical conditions. A 57-year-old man, with a medical history of human immunodeficiency virus, infective endocarditis, hepatitis C and orbital Aspergillus infection, was admitted to the intensive care unit following several episodes of TdP. The patient was being treated with methadone for opioid addiction and had started taking voriconazole 2 weeks prior for orbital Aspergillosis. He experienced multiple episodes of TdP with a prolonged QTc interval (>600 ms). The pronounced inhibitory impact of voriconazole on methadone metabolism via the cytochrome P450 (CYP)2B6 isoenzyme was identified as a probable cause of the arrhythmia. Voriconazole was subsequently temporarily withheld and the methadone dose was significantly reduced. The patient received an implantable cardioverter-defibrillator, did not experience additional episodes of TdP during hospitalisation, and was discharged from the hospital on day 13.