Health Canada has launched a review of the increasingly popular pharmaceutical drug tramadol – a move that could prompt the department to reverse its controversial, decade-old decision not to classify the medication as an opioid.
A change in the classification would put the drug on the same regulatory footing as opioids such as morphine, hydromorphone and oxycodone. It would also subject tramadol to tighter controls and enhanced reporting and record keeping.
Health Canada told The Globe and Mail late Tuesday that it is launching the review in response to recent data showing a dramatic rise in tramadol prescriptions. Once the assessment is complete, the department will determine whether the drug should be reclassified and regulated as an opioid. Currently, the painkiller is marketed in Canada as a non-opioid.
"Scheduling decisions are done in consultation with stakeholders, in order to balance all views," a spokesman said in an e-mail.
The review coincides with the release of new figures Wednesday from the Canadian Institute for Health Information (CIHI) that provide the most comprehensive publicly released national review of opioid-prescribing trends. The report reveals for the first time that doctors dispensed smaller quantities of opioids for shorter durations in each prescription between 2015 and 2016. While the institute describes the overall decline as "good news," it also highlighted concerns related to the growing use of two drugs – tramadol and hydromorphone.
Prescriptions for tramadol rose 30 per cent between 2012 and 2016. The CIHI report notes that Health Canada allows the drug to be marketed as a non-narcotic even though the department recognized back in 2007 that higher-dose formulations of tramadol "may be abused or misused in the future."
Wednesday's report is aimed at addressing gaps in Canada's ability to monitor a worsening and deadly opioid epidemic. Former health minister Jane Philpott pledged last November to create a central clearing house for tracking prescribing trends, emergency-department visits and overdose deaths.
Overprescribing is behind the opioid crisis, which has worsened in recent years with the arrival of illicit fentanyl, leading to a sharp spike in overdose deaths.
Canada ranks as the world's second-biggest consumer of pharmaceutical opioids.
A Globe and Mail investigation found that Ottawa and the provinces have failed to take adequate steps to stop the indiscriminate prescribing of opioids, a class of painkillers that includes hydromorphone, oxycodone and fentanyl.
The fact that tramadol is even included in CIHI's report is noteworthy. Because Health Canada considers tramadol to be a non-narcotic, the department does not list it as an opioid under the Controlled Drugs and Substances Act (CDSA). This puts the department out of step with international regulators. The World Health Organization and the United States' Drug Enforcement Administration classify tramadol as an opioid. As well, the manufacturers' own scientific descriptions describe tramadol as an "opioid analgesic."
"It kind of walks and talks like a narcotic, but it's not classified as one in Canada now," said report co-author Michael Gaucher, who is CIHI's director of pharmaceuticals and health workforce information services. He said the institute included the drug in its report in large part because CIHI follows WHO's classification system.
Because tramadol is not subject to the reporting requirements laid out in the CDSA, data about the extent of its abuse and misuse in Canada are lacking. South of the border, the U.S. Substance Abuse and Mental Health Services Administration found that the number of emergency-department visits related to the abuse or misuse of tramadol rose from 6,255 to 21,649 between 2005 and 2011 – an increase of roughly 250 per cent.
Tara Gomes, a scientist at Toronto's St. Michael's Hospital, described Ottawa's 2007 decision to continue to allow tramadol to be marketed as a non-opioid as a "strange" one. "We can start to see more people getting put on tramadol and being told that it is a safer alternative to other opioids, which is exactly what happened with OxyContin all those years ago, and we've seen what that did," she said.
Both Mr. Gaucher and Ms. Gomes spoke with The Globe before Health Canada's statement regarding the review.
When tramadol came on the market in Canada in 2005, it was sold as a low-dose product combined with acetaminophen – best known as the drug in Tylenol – and was not considered to pose a significant risk of dependence or abuse. By 2007, two drug companies gained approval for their once-daily, higher-dose formulations, even as one of those companies struggled to get the same product approved for sale in the United States.
That same year, Health Canada seriously considered – and then backed away from – a regulatory change that would have seen tramadol classified as a Schedule 1 drug under the CDSA.
According to a July 7, 2007, posting in the federal government's official newspaper, Health Canada recognized that higher doses of tramadol could lead to dependence in much the same way as other opioid painkillers, such as oxycodone and morphine.
"In particular, extended release formulations could be abused by dissolving, crushing, chewing or snorting the product, which may result in uncontrolled delivery of the opioid, and could result in overdose and death," the Canada Gazette posting said. "This regulatory amendment will benefit Canadians as the increased control of tramadol will serve to minimize its diversion, and the health risks associated with its illicit use."
The proposal was supported by provincial and territorial licensing bodies such as the College of Pharmacists of British Columbia and the Saskatchewan College of Pharmacists. However, the department faced resistance from officials from two tramadol manufacturers who expressed concern over the proposed change.
In the end, Health Canada did not go through with the regulatory change.
Two years later, in 2009, Health Canada conducted a second assessment of the health and safety risks associated with tramadol, but concluded that the drug did not warrant a reclassification as an opioid. "The available evidence suggested that tramadol had lower potential for abuse than other prescription opioids," the department said in its statement Tuesday evening.
The CIHI report also showed that doctors are prescribing higher-potency painkillers at an increasing rate, despite heightened awareness of the risks of addiction and overdoses associated with strong opioids.
Strong opioids accounted for 57.3 per cent of all prescription painkillers dispensed by retail pharmacies across Canada in 2016, a five-percentage-point increase from 2012.
Benedikt Fischer, a senior scientist at Toronto's Centre for Addiction and Mental Health, said it is not known whether the trend toward prescribing strong opioids has provided better care for patients – "probably not," he said – because the evidence for the efficacy of these drugs is limited.
"But it definitely has put a lot more people at higher risk, specifically in regard to misuse, potential addiction and also death," said Dr. Fischer, whose earlier research on opioid-prescribing trends is cited in the CIHI report.
The number of prescriptions for hydromorphone, a highly potent controlled-release drug, soared 57 per cent over the past five years, accounting for one of every five opioid prescriptions in 2016. The drug is largely behind the move away from weak opioids to potentially highly addictive strong painkillers.
Many doctors began shifting patients to hydromorphone in 2012, after the blockbuster drug OxyContin – a brand-name version of oxycodone made by Purdue Pharma – was no longer available in Canada. At one time, the country's top-selling long-acting opioid, OxyContin also became a lightning rod in the early 2000s, as reports of addiction and overdoses exploded. Purdue pulled the drug from the market; alternative painkillers, notably hydromorphone, filled the void.
"I think [hydromorphone] is the sleeper opioid drug, if you will, that we neglect," Dr. Fischer said. "It has almost the same profile as oxycodone, but we haven't really been paying a lot of attention to it. … The risks for dependency, misuse or overdose are very, very high. It can kill a lot of people."
Hydromorphone is five times stronger than morphine, and morphine, in turn, is five to 10 times stronger than codeine.
As part of the trend away from weak drugs, the number of prescriptions for codeine declined 10 per cent over the past five years. Still, it remains the most widely prescribed opioid in Canada. Among the less-potent opioids, tramadol, which is similar in potency to codeine, bucked the trend.
CIHI used numbers from health-data company Quintiles IMS to calculate that opioid prescriptions increased to 21.5 million in 2016, up 7 per cent over the five years. (The Globe reported in March that prescriptions for opioids totalled 19 million in 2016, based on data from Quintiles IMS that did not include tramadol and some other codeine products. Tramadol accounted for 70 per cent of the discrepancy.)
What the crisis looks like across the country
When it comes to the number of prescriptions dispensed during the study period, Quebec's data did not differ significantly from other provinces. But in terms of the actual quantity of opioids prescribed, the province was at the bottom of the low end – and by far. Doctors in Quebec are prescribing smaller amounts of opioids per prescription, whether through lower dosages or shorter treatments. In September, the Canadian Institute for Health Information (CIHI) released a report that found Quebec also had the lowest rate of opioid-related hospitalizations. "Understanding the relationship between opioid prescribing and harms such as hospitalizations in Quebec could have valuable implications for best practices in the future," Wednesday's report says.
NEWFOUNDLAND AND LABRADOR
Health professionals in the Atlantic province prescribed the second-largest quantity of opioids per 1,000 people, behind only Alberta. Unlike Alberta, which saw its opioid quantities decrease between 2015 and 2016, Newfoundland and Labrador saw a 0.8-per-cent rise in the amount of opioids prescribed per 1,000 during the same period. Only one other province – Saskatchewan – saw an increase in quantities, up 0.5 per cent. Benedikt Fischer, a senior scientist at Toronto's Centre for Addiction and Mental Health, said that while much of the focus has been on the crisis unfolding in the west, and to some extent Ontario, "some of the lingering problems are in the east, where we're not paying so much attention."
BRITISH COLUMBIA AND NOVA SCOTIA
The largest decreases in the quantity of opioids prescribed per 1,000 people between 2015 and 2016 were seen in British Columbia and Nova Scotia, down 11.8 per cent and 6 per cent respectively. The report notes that the College of Physicians and Surgeons in both of those provinces endorsed new opioid-prescribing guidelines issued by the U.S. Centers for Disease Control and Prevention soon after they came out in March, 2016. Experts said the U.S. guidelines – which address treating patients with acute pain, where opioid addiction often begins – could be among the reasons B.C. and Nova Scotia saw their quantities decline between 2015 and 2016. Increased awareness of the epidemic in hard-hit B.C., for example, may also have contributed to the decrease in the quantity of opioids prescribed there.