High-strength opioid formulations: the case for a ministerial recall

Dear Editor,

The Canadian Society of Palliative Care Physicians would like to comment on the proposal by Herder and Juurlink that the federal Minister of Health should recall from the Canadian market all high strength opioid formulations equal to 100mg morphine equivalent dose and above (1).

While we acknowledge the current opioid crisis and the recently revised opioid prescribing guidelines that apply to non-cancer pain, we have serious concerns about this proposed recall in the context of cancer pain and patients with palliative care needs including those who also suffer from opioid use disorder. The BC Practice Standard specifically indicates that such patients should not be included in the guideline (2). Our own position statement on access to opioids for patients requiring palliative care (3) and the WHO cancer pain relief document (4) recommend the use of opioids for cancer pain at doses that are titrated up to effect and tolerability with no maximum dose. We are currently producing Opioid Wisely guidelines regarding this matter for Choosing Wisely Canada.

Patients with cancer pain sometimes require large doses of opioids to control their pain, even well above 200mg oral morphine equivalent (5-7). Patients with opioid use disorder and cancer pain are often treated in addition to their Opioid Agonist Therapy with long acting oral once daily or transdermal opioid preparations (8), often at high doses due to opioid tolerance, following careful risk assessment and management (8).

Limiting the availability of high-strength opioid formulations could create difficulties and barriers for patients with cancer pain and other palliative needs. Having to take multiple doses of a lower strength preparation in the context of complex drug regimens for cancer could increase the risk of errors and poor compliance. This could also create a barrier to obtaining prescriptions from family doctors who are already cautious about prescribing opioids in large quantities. For patients with palliative care needs who also have opioid use disorder, and need high strength additional opioids for pain, it is safer to prescribe a single large once-daily supervised oral ingestion or transdermal application rather than multiple lower dose preparations spread throughout the day (9). Restricting access to products that enable this practice will increase rather than decrease the risk of diversion. The use of multiple lower dose transdermal patches could enable diversion, as the patient may be able to tolerate a small decrease in dose while some of the patches are diverted.

Ontario’s Palliative Care Facilitated Access program offers a possible solution. As of 2016, prescribing of high-strength opioid formulations is restricted to a prescriber or contact with a prescriber registered by the licensing body as a palliative care physician. This has reduced prescriptions for these formulations while maintaining access for those who need them for palliative care. All practitioners need to continue to work together to ensure the care needs of all patients are met.

Dr. Leonie Herx
President, Canadian Society of Palliative Care Physicians

References:
1. Herder M, Juurlink D. High-strength opioid formulations: the case for a ministerial recall. CMAJ 2018;190(48):E1404-E1405
2. College of Physicians and Surgeons of British Columbia. Practice standard - safe prescribing of opioids and sedatives. 2018. [updated 2018 June 4; cited 2018 Dec 6]. Available from www.cpsbc.ca/files/pdf/PSG-Safe-Prescribing.pdf
3. Canadian Society of Palliative Care Physicians. Position statement on access to opioids for patients requiring palliative care. 2016. [cited 2018 Dec 6]. Available from www.cspcp.ca/wp-content/uploads/2014/10/CSPCP-Position-Statement-on-Acce...
4. World Health Organization. Cancer pain relief: with a guide to opioid availability, 2nd ed. [Internet]. Geneva: World Health Organization. 1996. [cited 2018 Dec 6]. Available from http://www.who.int/iris/handle/10665/37896
5. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD003868.
6. Portenoy RK, Ahmed E. Principles of Opioid Use in Cancer Pain. J Clin Oncol 2014;32:1662-1670
7. Varilla V, Schneiderman H, Keefe S. No Ceiling Dose: Effective Pain Control with Extraordinary Opiate Dosing in Cancer. Connecticut Medicine 2015;79(9):521-524
8. Passik SD, Kirsh KL. Opioid Therapy in Patients with a History of Substance Abuse. CNS Drugs 2004;18(1):13-25
9. Kirsh KL, Passik SD. Palliative Care of the Terminally Ill Drug Addict. Cancer Investigation 2006; 24: 425-431

As a family doctor and palliative care enhanced competency resident, I was frustrated to read Herder and Juurlink’s editorial recommending a ministerial recall for high-strength opioid formulations. The authors’ well-intentioned suggestion would bring considerable harm to patients suffering with pain from incurable diseases, particularly advanced cancer.

Many of my patients have metastatic disease characterized by extensive bone disease and soft tissue invasion. They are able to maintain good quality of life and function at home, partly through the benefits provided by the very high-dose opioid formulations demonized in the article. Without them, they suffer from debilitating pain, and associated anxiety, depression, and loss of function which can lead to hospital admission and even earlier death.

The authors cite recent clinical practice guidelines on chronic noncancer pain to support their recommendation. These guidelines remain controversial, based on consensus and not on evidence, and they specifically exclude cancer pain from their scope. While we might wish cancer did not exist, 1 in 2 Canadians will develop cancer in their lifetimes, half of those will die from it, and many of them will have pain requiring opioid analgesia. Dismissing the pill burden in these patients as a “relatively minor inconvenience” trivializes the constant pall of medical care over their daily lives.

The comparison to thalidomide is pertinent because it too is a drug with utility in treating cancer, and it remains available for patients with multiple myeloma. The fact that a drug can be harmful in some patients is not a reason to deny it to all patients – if that were the case we’d have no pharmaceuticals at all.

A ministerial recall is an inappropriate sledgehammer that would have questionable benefit while undoubtedly causing harm to my patients. A more nuanced approach, educating clinicians and patients about the harms of high-dose opioids in chronic non-cancer pain, tracking doses, and optimizing non-opioid management would offer greater benefit while minimizing inadvertent harms of prohibition.

This marks a new low in the discussion of the so-called perils of therapeutic opiates. The authors advise Ottawa to recall "high dose" formulations of medical opiates. But what constitutes a "high" dose, when opiate dosing is properly done on a customized basis?

Whatever "high" means here, recent research suggests, not for the first time, that lower, not higher, doses wreak greater harm (https://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2018.304590?journ...). In an open letter he signed last week disparaging forced tapering (https://academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pny...), Dr Juurlink himself acknowledges this.

Research also shows that prescribed opiates are not particularly lethal at any dose. The largest study to date, of nearly 2.2M Americans, pegs the annual overdose death rate from prescribed opiates at a mere 0.022% (https://academic.oup.com/painmedicine/article/17/1/85/1752837).

Truly confounding and downright weird is the authors' claim that more is less: that, say, two 50 mcg patches of transdermal fentanyl are safer than one 100 mcg patch. They're not, of course. "Pill burden"---making patients take a bunch of pills instead of one---is not a "relatively minor inconvenience"; it's trouble. The fewer pills or patches you use to achieve a dose, the more likely you are to get your dose right. Dr Juurlink, a pharmacist, doesn't seem to know that, nor does he seem to know or care that lower-dose formulations used in multiples cost patients more. That matters, since many Canadians with chronic pain don't have jobs with insurance plans and aren't living large on their disability pensions. What the authors are actually saying is that lower-dose formulations can be weaponized against users when they're employed to prompt patients to taper or end their therapy.

Whatever we think of the laundry list of "harms" the authors cite, we should be asking every time we hear it---and we hear it frequently---why physical dependence is bad when it involves medical opiates but not when it involves the many other drugs we become dependent on. Note, too, the judicious use of "likely" throughout the piece; it's a proxy for proof. Three of the six papers on opiates the authors cite are Dr Juurlink's own work. Two come from his compatriots. How do we know, then, beyond Dr Juurlink, that these "harms" are dose-dependent?

Moreover, there's plenty of evidence that doses of 200 to 400 MME afford more benefit than harm, as the AMA told us last month (https://www.cato.org/blog/better-late-never-0). Conversely, there's no evidence, as claimed here, that doses are continually escalated in patients with chronic pain. To the contrary, when effective doses are reached, they plateau.

But why should we restrict medically-managed opiates at all, when coroners' reports and the RCMP tell us repeatedly that it's not the medical supply but rather Chinese crime rings that are causing our overdose deaths? That's the evidence we should be looking at. Herder and Juurlink are emperors with no clothes, and it's time we stood up and said so.

In response to Herder and Juurlink's call for the federal Minister of Health to recall high-strength opioid formulations, I argue that the risk of injury to the health of Canadians from such a policy would be greater than any such risk from these medications themselves.

In my opinion, recalling high-strength opioids is unlikely to change opioid prescribing patterns to any great extent. It does, however, have the very real potential to increase the amount of opioids being diverted to street use by increasing the number of opioid pills being prescribed and dispensed. It is also likely to further limit access to opioids for individuals dealing with chronic pain without addressing their underlying dependency or the tremendous lack of access to other chronic pain therapies that exist across Canada, leaving these individuals vulnerable to seeking opioids from street sources and placing themselves at a much greater risk of overdose. Last, recalling high-strength opioids may place another barrier in the way of increasing access to prescribed opioids as a harm reduction measure, a necessary step in dealing with the ongoing crisis of overdose deaths due to contaminated street drug supplies.

The authors themselves cite the 2012 move to change the formulation of OxyContin, which had the unintended consequence of increasing the demand for fentanyl and creating a black market opportunity. I hope we have learned from this example that isolated policy initiatives to change the highly complex situations of opioid overprescribing and toxic street drugs need careful analysis given the very real risk of creating net harm.