Oxycodone and QTc prolongation

Editor, – Thank you to Michael McDonough for his comprehensive article on the safe prescribing of opioids (Aust Prescr 2012;35:20-4 ). In particular, Table 1 provides useful recommendations for the monitoring and management of possible emerging adverse effects.

The inclusion of oxycodone as a medication which prolongs QTc was surprising. This precaution does not appear in other sources of information discussing oxycodone, such as the reference cited for Table 1¹ , the approved product information for oxycodone, the Australian Medicines Handbook,² Therapeutic Guidelines³ or the database which records medications that prolong QTc (www.qtdrugs.org). However, there has been research published which supports the occurrence of prolonged QTc by oxycodone in a dose-dependent manner.⁴ Is there any other literature that the author can refer us to which supports the prolongation of QTc by oxycodone?

The suggested strategy to manage this potential adverse effect in his article is to recommend an ECG. Given that the prescribing of oxycodone and oxycodone-related deaths have increased in Australia since 2002,⁵ does the author, as a practical consideration, advise that in all cases an ECG be performed before the initiation of all formulations of oxycodone?

Margaret Jordan
NPS facilitator
Illawarra Shoalhaven Medicare Local

Tania Colarco
Clinical pharmacist and NPS facilitator
Drug and Therapeutics Information Service (DATIS)
Repatriation General Hospital, Adelaide

Kirsty Lembke
Program officer
NPS, Sydney

Michael McDonough, author of the article, comments:

Thank you for raising two further questions from my article. As you have noted, I was also referring to the article about dose-dependent QTc prolongation by oxycodone.⁶

The concern is that drugs like oxycodone and others yet to be associated with QT prolongation appear to be identified later rather than sooner. We remain uncertain about the precise mechanism of fatal toxicity in both methadone- and more recently the rising number of oxycodone-related deaths in Victoria⁷ and the USA.⁸ However, the possibility, even if somewhat small, that QT prolongation may be a predisposing factor together with other arrhythmogenic risk factors – such as hypokalaemia, hypomagnesaemia, other drug interactions and heart disease – should be considered.

I believe baseline ECG recording is not appropriate as a screening recommendation because there is no evidence to guide the implementation of such a strategy. Also, this might give rise to concerns about degrees of variation in the QTc interval in various patients and potentially lead to excessive investigation and possibly over-intervention. Consensus recommendations about QTc monitoring in patients on methadone also draw attention to the controversies surrounding the management of degrees of QTc prolongation and the complexities involved in ‘risk versus benefit’ analyses in this scenario.⁹

I believe an annual ECG recording in the context of long-term and especially high-dose oxycodone treatment would constitute reasonable care and is preferable to not doing so. Furthermore, undertaking an ECG in any patient on oxycodone and with additional risk factors (mentioned above) would no doubt be a more compelling recommendation.