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Published: 5 September 2014

Methadone - Don't Break Your Heart (QT Prolongation)

Prescriber Update 35(3): 35
September 2014

Key Messages

  • QT prolongation has been reported in patients receiving doses of methadone greater than 100 mg/day.
  • ECG monitoring is recommended before dose titration above 100 mg/day and at seven days after titration in patients with no risk factors for QT prolongation.


Methadone is an opioid analgesic for moderate to severe pain used in the treatment of opioid dependence. QT prolongation has been reported in patients receiving doses above 100 mg/day with no prior cardiac history.

QT prolongation is used as a surrogate marker for the risk of developing the potentially fatal arrhythmia Torsades de Pointes (TdP).

The risk of QT prolongation with methadone is increased in the presence of other risk factors. These include a genetic predisposition or pre-existing QT prolongation, increasing age, female gender, hypokalaemia or hypomagnesaemia, and medicine interactions1. An up-to-date database of medicines with the potential to cause QT prolongation/TdP, including a separate list of medicines to be avoided by patients with congenital long QT syndrome, is available on-line at www.qtdrugs.org.

In patients with risk factors for QT prolongation, ECG monitoring is recommended prior to methadone treatment, at dose stabilisation, after dose increases, or after starting any potentially interacting medicine2.

In patients without risk factors for QT prolongation, ECG monitoring is recommended before dose titration above 100 mg/day and at seven days after titration2.

The Centre for Adverse Reactions Monitoring (CARM) has received five reports of QT prolongation and/or TdP with the use of methadone at doses between 110 and 160 mg/day. One of these cases reported a cardiac arrest secondary to TdP.

Medsafe is currently working with the relevant sponsors to ensure all methadone data sheets contain these new recommendations.

References:
  1. Medsafe, 2010. Drug-induced QT prolongation and Torsades de Pointes - the facts. Prescriber Update 31(4): 27-29. URL: www.medsafe.govt.nz/profs/PUArticles/DrugInducedQTProlongation.htm (accessed 10 July 2014).
  2. Thornton & Ross Ltd, 2014. Methadone 1mg/ml Oral Solution BP - Sugar Free SPC 12 March 2014. URL: www.medicines.org.uk/emc/medicine/25339 (accessed 10 July 2014).
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