Summary Safety Review - Hydromorphone Controlled Release Capsules - Assessing the Increased Risk of Serious Infections Linked to the Injection of the Content of the Capsules into Veins

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2020-09-10

Product

HYDROmorph Contin and generic hydromorphone controlled release capsules.

Potential Safety Issue

Increased risk of serious infections such as infection of the inner lining of the heart chambers and valves (infective endocarditis), and bloodborne infections caused by human immunodeficiency virus (HIV) or hepatitis C virus (HCV) linked to the injection of the content of oral hydromorphone controlled release capsules into the veins.

Key Messages

  • Hydromorphone controlled release capsules are prescription opioid drugs authorized for sale in Canada to be taken by mouth (orally) for the long term management of pain when:
    • the pain is severe enough that it needs daily, around-the-clock pain medication.
    • other treatment options are not working.
  • Health Canada reviewed the potential increased risk of infections, such as infective endocarditis (IE) and bloodborne infections caused by human immunodeficiency virus (HIV) or hepatitis C virus (HCV), related to the problematic use of oral hydromorphone controlled release capsules (injection of the content of the capsules into veins) among people who inject drugs. This safety review was triggered by a study published in the Canadian Medical Association Journal (CMAJ)1 and discussions between Health Canada and the authors of the study.
  • Health Canada's review of the available information could not link the increased risk of IE and bloodborne infections caused by HIV or HCV with the injection of the content of the capsules into veins compared to the injection of other prescription opioids because of a lack of information.
  • Health Canada will continue to monitor the safety of hydromorphone-containing products including hydromorphone controlled release capsules.

Overview

Health Canada reviewed the potential increased risk of infections (such as IE and bloodborne infections caused by HIV or HCV) related to the problematic use of the oral hydromorphone controlled release capsules (injection of the content of the capsules into the veins) when compared to other oral opioid products among people who inject drugs. The review was triggered by a study published in the CMAJ and discussions between Health Canada and the authors of the study.

The article described that the equipment (for instance, cookers and filters) used to prepare the content of the hydromorphone controlled release capsules for injection was shared and re-used more often for hydromorphone than for other opioid products. The authors proposed that this practice could lead to more germs being present and, as a result, could increase the chances of spreading infections such as IE, and bloodborne infections caused by HIV or HCV. It was further suggested that the equipment is reused and shared more often because it is more difficult to extract hydromorphone from the other components (excipients) in the capsules than it is for other opioid products (for instance, extracting oxycodone from controlled release products) and users believe that the equipment may contain residual hydromorphone.

This safety review does not apply to the authorized oral use of hydromorphone controlled release capsules.

Use in Canada

  • At the time of the review, the following hydromorphone capsules and tablets were marketed in Canada:
    • hydromorphone hydrochloride controlled release capsules (HYDROmorph Contin and its generic version, Apo-HYDROmorphone CR), and
    • hydromorphone hydrochloride tablets (Dilaudid and its generic versions: Apo-HYDROmorphone, Teva-HYDROmorphone and pms-HYDROmorphone).
  • HYDROmorph Contin was the first hydromorphone controlled release product for oral use authorized in Canada in 1994.
  • From 2014 until the end of September 2019, HYDROmorph Contin has been the most prescribed oral hydromorphone product (about 10 million prescriptions), followed by pms-HYDROmorphone (about 9 million prescriptions) and Dilaudid (about 3 million prescriptions). There were approximately 25 million prescriptions for all oral hydromorphone products during this period.

Safety Review Findings

  • Health Canada's safety review looked at population-based studies (11 epidemiological studies, one case series, 5 cross-sectional studies and one systematic review), 2 in vitro studies, 3 review articles, and 8 individual Canadian case reportsa.
  • Health Canada's review of the available evidence from these studies and reports, did not find a direct link between the use of oral hydromorphone controlled release capsules injected into the veins and an increased spread of IE and bloodborne infections caused by HIV or HCV. This was due to lack of information on the number of:
    • patients with IE, and bloodborne infections caused by HIV or HCV among people who inject drugs by region across Canada, and
    • people who use opioids problematically as well as how they use them.
  • There is evidence in the epidemiological studies that HIV, HCV and IE outbreaks have occurred in some regions of Canada and in other countries that have been associated with the injection of different oral prescription opioids (such as oxymorphone and oxycodone) into the veins. This situation could be related to the wide availability of certain prescription opioids in the community, and high-risk injection drug use practices and behaviours.
  • Oral hydromorphone is widely prescribed in Canada and its availability seems to be one of the key factors related to its problematic use. From 2014 through 2019, the number of prescriptions dispensed from retail pharmacies for hydromorphone was more than double (about 25 million) the number of prescriptions for other oral opioids, including morphine (about 11 million) and oxycodone (about 10 million).
  • Health Canada's review of the 8 Canadian case reports did not find a link between the use of hydromorphone controlled release products injected into the veins and an increased risk of infections such as IE and bloodborne infections caused by HIV or HCV because:
    • detailed medical information in the reports was not available,
    • there were no reports confirming injection drug use of hydromorphone controlled release products, and
    • persons described in the cases used several drugs at the same time, which made it difficult to assess the effect of hydromorphone controlled release capsules.
  • The safety review used estimates found in the literature as it was challenging to obtain accurate information on the number of people infected with IE and bloodborne infections caused by HIV, and HCV, and the patterns of problematic drug use in Canada. These populations vary across Canada based on their access to health care, illnesses, living conditions, injection drug practices and participation in needle exchange programs.
  • Overall, a higher number of new cases of IE and bloodborne infections caused by HIV and HCV was observed in the epidemiological studies reviewed among people who inject drugs compared to the general population. The use of non-sterile injecting equipment, sharing the injecting equipment and unprotected sex are known risk factors to getting these types of infections, regardless of the type of drug used.

Conclusions and actions

  • Health Canada's review of the available evidence did not find a direct link between the use of oral hydromorphone controlled release capsules injected into the veins and an increased risk of the spread of IE and bloodborne infections caused by HIV or HCV.
  • More population-based (epidemiological) information is needed to understand how oral prescription opioids are prescribed as well as how they are problematically used by injection in Canada. The Department will work with the Drug Safety and Effectiveness Network (DSEN) to gather additional information on this topic.
  • Health Canada will also inform manufacturers of controlled release opioid formulations that they should be monitoring the risk of increased IE and bloodborne infections caused by HIV or HCV with improper use of these formulations as part of their risk management plans and report the results to Health Canada.
  • Health Canada will continue to monitor safety information involving hydromorphone-containing products to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.
  • Health Canada will continue to share information with different stakeholders such as provincial and territorial governments, municipalities, health organizations, substance use experts, and people who inject drugs to improve the content of educational programs on problematic use.

Additional information

Manipulating opioid products and using them in ways they are not intended to be used can lead to serious consequences, including overdose and death.

Additional information on opioid overdose, short and long-term effects of opioids, safe use of opioids, and where to get help is available at About Opioids.

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of this drug, both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Weir MA, Slater J, Jandoc R, et al. The risk of infective endocarditis among people who inject drugs: a retrospective, population-based time series analysis. CMAJ January 28, 2019 191 (4) E93-E99

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.

Report a problem or mistake on this page
Please select all that apply:
Date modified: