Other safety alerts
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| Canada: Summary Safety Review: Prescription Opioids (buprenorphine, butorphanol, codeine, diamorphine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, nalbuphine, normethadone, oxycodone, tapentadol and tramadol): Assessing the potential risk of esophageal dysfunction with long-term use |
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Product
Prescription opioids (buprenorphine-, butorphanol-, codeine-, diamorphine-, fentanyl-, hydrocodone-, hydromorphone-, meperidine-, methadone-, morphine-, nalbuphine-, normethadone-, oxycodone-, tapentadol- and tramadol-containing products)
Potential Safety Issue
Esophageal dysfunction (impaired function of the esophagus) with long-term use (daily for a few weeks) of prescription opioids
Key Messages
- Health Canada’s review found a possible link between the long-term use of prescription opioids and the risk of esophageal dysfunction.
- Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for prescription opioids to include the risk of esophageal dysfunction with long-term use.
Overview
Health Canada reviewed the potential risk of esophageal dysfunction with the long-term use of prescription opioids. The safety review was triggered by Health Canada’s identification of several scientific studies reporting a possible association between the long-term use of opioids and esophageal dysfunction, confirmed by tests measuring how well the esophagus is working (esophageal pressure testing). Health Canada’s review did not include non-prescription opioid-containing products since this risk has not been reported with these products.
Use in Canada
- Prescription opioids are authorized in Canada for the treatment of various conditions including certain types of pain, opioid use disorder and chronic non-productive cough.
- Prescription opioids are widely used and have been marketed in Canada for over 50 years. The prescription opioids included in this safety review are: buprenorphine, butorphanol, codeine, diamorphine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, nalbuphine, normethadone, oxycodone, tapentadol and tramadol. These opioids are available in various formulations and combinations under different brand names. Generic versions are also available.
- While the number of prescriptions dispensed for the majority of opioids has decreased from 2018 to 2023, the overall number of prescriptions remains high.
Safety Review Findings
- Health Canada reviewed the available information from searches of the Canada Vigilance database and the scientific literature.
- At the time of the review, Health Canada had received 28 Canadian reports of esophageal dysfunction in patients taking prescription opioids. However, none of these cases met the criteria for further assessment to determine if there was a link due to several contributing factors, such as: incomplete information in the reports, lack of information about when or how long the opioid was taken relative to the esophageal dysfunction, or the reported diagnosis was not confirmed by esophageal pressure testing.
- Health Canada reviewed 14 international cases of esophageal dysfunction in patients taking prescription opioids. Of the 14 cases, 3 were found to be probably linked to the use of prescription opioids and 11 were found to be possibly linked. One death occurred among the 3 cases found to be probably linked, although the death was unlikely to be linked to the use of prescription opioids.
- The patients in the 14 cases were taking doses equivalent to between 30 and 300 mg of morphine per day, with a midrange daily dose of 67.5 mg. Esophageal dysfunction was more likely to occur in patients taking a higher daily opioid dose. The time to onset of symptoms ranged from several weeks to months, with the most common symptoms reported being difficulty swallowing, gastroesophageal reflux and chest pain.
- Health Canada also reviewed articles published in the scientific literature, which identified potential biological mechanisms that may explain how the long-term use of prescription opioids could lead to esophageal dysfunction.
Conclusions and Actions
- Health Canada’s review found a possible link between the long-term use of prescription opioids and the risk of esophageal dysfunction.
- Health Canada will work with the manufacturers to update the CPM for prescription opioids to include the risk of esophageal dysfunction with long-term use.
- Health Canada will continue to monitor safety information for prescription opioids, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.
Please refer to the following website in Health Canada for details:
http://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1750686507938
In Hong Kong, there are registered pharmaceutical products containing buprenorphine (4 products), codeine (346 products), fentanyl (14 products), meperidine (pethidine) (7 products), methadone (2 products), morphine (15 products), nalbuphine (1 product), oxycodone (14 products) and tramadol (42 products). These products are pharmacy-only medicines or prescription-only medicines. There is no registered pharmaceutical product containing butorphanol, diamorphine, hydrocodone, hydromorphone, normethadone and tapentadol. So far, the Department of Health (DH) has received adverse drug reaction with regard to codeine (4 cases), fentanyl (6 cases), meperidine (pethidine) (5 cases), methadone (5 cases), morphine (11 cases), oxycodone (2 cases) and tramadol (9 cases) but these cases were not reported as esophageal dysfunction. The DH has not received any case of adverse drug reaction with regard to buprenorphine and nalbuphine.
Related news regarding the long-term use of opioids was previously issued by the United States Food and Drug Administration, and was posted on the Drug Office website on 1 Aug 2025. The risk of inhibited gastrointestinal motility associated with the use of opioid analgesics is documented in overseas reputable drug references such as the “Martindale: The Complete Drug Reference”. The DH will remain vigilant on any safety update of the drugs issued by other overseas drug regulatory authorities for consideration of any action deemed necessary.
Ends/Monday, Sep 29, 2025
Issued at HKT 17:45
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