Methadone and prolongation of QT interval

• there is a risk of QT interval prolongation in patients taking methadone, especially those on high doses (1)
  • there is evidence that very-high-dose methadone may be associated with torsade de pointes (2)
• recommended that patients with the following risk factors for QT interval prolongation are carefully monitored whilst taking methadone:
  • heart or liver disease, electrolyte abnormalities, concomitant treatment with CYP 3A4 inhibitors, or medicines with the potential to cause QT interval prolongation (1)
    • also any patient requiring more than 100mg of methadone per day should be closely monitored (1)
    • the RCGP guidance also notes that the risk of QT-interval prolongation may be dose-dependent (3)
      • "..methadone may be a risk factor for QT prolongation and torsade de pointes with a possible dose-dependent action... recommends monitoring for patients on high dose methadone (>100 mg daily) and with other QT interval prolongation risk factors where appropriate.."

Reference:

• (1) Current Problems in Pharmacovigilance 2006;31:1-12.
• (2) Krantz MJ et al. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med. 2002 Sep 17;137(6):501-4.
• (3) RCGP (2007). Drug misuse and dependence: UK guidelines on clinical management