Correspondence: Oxycodone; Morphine formulations; Patients expectations

We thank our correspondent for his candid comments which add to the debate on the challenges of prescribing opioids for use in the community.

In the article “Oxycodone – How did we get here and how do we fix it?” (BPJ 62, Jul, 2014), we discussed the available evidence on the efficacy and adverse effects of oxycodone. The problem is that there are very few high quality, head-to-head trials comparing oxycodone with other strong opioids. Perhaps it is better to view the evidence in terms of what is not proven, which would lead to the conclusion that we cannot say for certain that oxycodone is superior to morphine in terms of adverse effects. There is some evidence that oxycodone may be less associated with nausea and vomiting than morphine, but there is also some evidence that it is more associated with constipation. If in balance, these two medicines are considered similar in efficacy and adverse effect profile, it then comes down to a decision based on other risks and benefits. The emerging misuse and addiction problems with oxycodone in New Zealand, coupled with the lessons learnt from other countries that have been dealing with these problems, swings the balance in favour of morphine, if a strong opioid is required at all. This is actually the bigger message in the “oxycodone story” – with the exception for use in malignant pain, why are we prescribing strong opioids in the community at all?

Although the prompt to explore and write about medicines is often directed at those medicines with significant cost to the health system, in order to reap the health benefit of this expenditure the medicines need to be used in accordance with best available evidence and practical application of this evidence, which is the thrust of many of our articles. This is true of medicines that are relatively inexpensive and used frequently in medicine (often general practice), as it is true of more expensive treatments that are used in a very few patients. Cost is relevant to many patients, who make cost-benefit decisions daily in all aspects of their lives. Patients are sometimes flabbergasted when they find out the actual cost of their medicine, as opposed to the $5 prescription fee they pay at the pharmacy.

In the case of oxycodone, we have collaborated with both PHARMAC and Medsafe to highlight the general safety issues with this medicine, and cost has not been a significant factor in these discussions.

As for the final point - the amount of strong opioids being used in New Zealand is increasing, as evidenced by national pharmaceutical dispensing data. It is difficult to say with certainty what is driving this increased use, but it is likely to be a combination of many factors, including widespread use of strong opioids for both malignant and non-malignant pain, misuse and misappropriation of prescriptions and pressures on the health care system to meet demands for definitive treatment of painful conditions.

We hope that the article in this edition, “Helping patients cope with chronic non-malignant pain: it’s not about the opioids” may at least give clinicians some tools to help stem the tide of opioids.

It is pleasing that points made in the article “Oxycodone – How did we get here and how do we fix it?” (BPJ 62, July, 2014) have been found to be relevant to our correspondent and useful in his clinical practice.

It is also interesting to review some of the history of the introduction of m-Eslon and oxycodone in New Zealand. When prescribing a new product, be it a new medicine (in the case of oxycodone) or a new product formulation (in the case of m-Eslon) there will be a period of gaining experience with prescribing it, understanding its effect and effectiveness for patients, and learning where it fits into your own, and wider, clinical practice.

As substantiated by our correspondent, when m-Eslon became funded on the Pharmaceutical Schedule there were anecdotal reports that its analgesic effect did not always last the expected 12-hour duration; this may have been more prevalent at lower daily doses of m-Eslon. However, there have also been reports of the MS Contin formulation not controlling cancer pain using a 12-hourly dosing regimen: in an review of early studies of patients with moderate to severe cancer-related pain who were transferred from a 4-hourly, immediate-release morphine dosing regimen to 12-hourly, sustained release MS Contin, 93% of patients were successfully treated with 12-hourly MS Contin, but 7% required 8-hourly MS Contin dosing.*

Similarly, we have learned more about oxycodone and its formulations as experience has been gained. So is it the medicine, the new formulation, the patient or the change?

* Kaiko R, Grandy R, Oshlack B, et al. The United States experience with oral controlled-release morphine (MS Contin tablets). Cancer 1989;63:2348-54.

Response from Dr Jeremy McMinn:

Dr Wright’s experiences are common – “inheriting” patients in whatever capacity, e.g. as a locum, present compelling opportunities to re-consider diagnosis and the consequences of earlier treatment. The patients on long-term opioids seeking escalating doses demonstrate the need to review the original treatment contract in the light of incomplete recovery or, worse, emerging iatrogenic deficits.

How to address this depends on which prescriber(s) will be able to see a revised treatment approach through. The duration of the cover will determine how much can be tackled – often setting the scene for change (but not actually making changes) is a powerful tool to hand over to the returning doctor, who may be grateful for the opportunity to use a colleague’s second opinion to good effect. But if you are taking over the prescribing for the longer haul, this needs to fit with your prescribing integrity – after six months, every treatment contract with the patient is yours, not the earlier doctor’s!

The combination of oxycodone and naloxone has much false promise, in my view. The key concern is that this maintains a perspective that chronic opioids are a normal, valid, readily used intervention – we should be questioning this with wise and grave doubt.

As for the alleged effects on constipation and abuse potential, it is important to distinguish between evidence and marketing. There is little good evidence for oxycodone, but one can extrapolate from other combination attempts. Naloxone, when combined with buprenorphine (in the form of Suboxone), has no clinically useful effect on constipation. Research by Larance et al*demonstrated that even buprenorphine with naloxone in a buccal film preparation was still subject to significant rates of abuse. That having been noted, buprenorphine alone may have a greater abuse potential: the same may be true for oxycodone alone.

The analogy of low tar cigarettes springs to mind – the gains are so little, but the product has a seductive sense of being safer.

* Larance B, Lintzeris N, Ali R, et al. The diversion and injection of a buprenorphine-naloxone soluble film formulation. Drug Alcohol Depend 2014;136:21-7.

We apologise for this oversight. You are correct, this was just a graphic and is not a real dispensing container. We have corrected this graphic in our online version of this article.