Torsades des Pointe (TDP) associated with methadone maintenance therapy (MMT) in a patient with hepatitis‐induced cirrhosis

Drug‐induced prolongation of the QT interval can result in TdP, reflecting bradycardia or delay of the rapidly activating component of the delayed rectifier potassium current. Methadone has been associated with QT prolongation and TdP, generally at daily doses>500 mg/d, although episodes in patients taking as little as 65 mg/d have been observed. We describe a 55 year old man with a history of 30 y of MMT and concomitant hepatitis C‐induced cirrhosis who experienced two episodes of syncope over five months reflecting QT prolongation resulting in TdP. In the first episode, the patient experienced several intervals of TdP associated with a prolonged corrected QT interval (QTc) of 494 msec while taking 300 mg of methadone daily. Discontinuation of the methadone resulted in a decrease in the QTc: 450 msec at 72 h and 417 msec at 96 h. 5 months later, the patient presented with a prolonged QTc of 553 msec and TdP associated with taking 125 mg of methadone daily. Discontinuation of methadone resulted in normalization of the QTc by 48 h, a time at which the serum methadone level was 49 ng/ml. Re‐induction of a prolonged QTc and TdP with re‐challenge followed by normalization of the QTc upon de‐challenge supports methadone as the causative agent, presumably reflecting accumulation secondary to cirrhosis and impaired clearance. This case report highlights the risk of electrophysiological events in patients with advanced liver disease administered standard doses of methadone. Clinical Pharmacology & Therapeutics (2004) 75 , P45–P45; doi: 10.1016/j.clpt.2003.11.167