Methadone Treatment of Opioid Dependence and Potential Risk of Lack of Effect when Switching between Different Products

Starting date:
July 17, 2020
Posting date:
July 17, 2020
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals, Hospitals
Identification number:
RA-73547

Last updated:

Audience

Healthcare professionals including general practitioners, family physicians, nurse practitioners, pharmacists and addiction specialists.

Key messages

  • A safety review completed by Health Canada has found that there may be a link between switching methadone-containing products used to treat opioid dependence and the risk of lack of effect, which may present as withdrawal symptoms, although the reason for this is unclear.
  • Healthcare professionals should be aware that:
    • Some patients may experience withdrawal symptoms after being switched from one methadone-containing product to another; these patients should be clinically managed and monitored regularly.
    • Dose adjustments may be necessary in some patients. 
    • Withdrawal symptoms can lead to a failure to remain in treatment and subsequent problematic substance use, which can lead to serious harms.
  • Health Canada will be working with the manufacturers to update the Canadian product information to warn of this potential safety issue.

     

Issue

Health Canada has completed a safety review which examined how patients respond when they are switched from one methadone-containing product to another for the treatment of opioid dependence. The review found that there may be a link between switching methadone-containing products and the risk of lack of effect which may present as withdrawal symptoms. Health Canada is informing healthcare professionals of this safety issue and will be updating the product information to warn of this safety issue.

Products affected
Brand/
Product Name
Medicinal Ingredient and Strength DIN Manufacturer
Jamp Methadone Oral Concentrate* methadone hydrochloride oral concentrate, 10 mg/mL 02495783 Jamp Pharma Corporation
Metadol-D methadone hydrochloride oral solution, 1 mg/mL 02247374 Paladin Labs Inc.
Metadol-D methadone hydrochloride oral concentrate, 10 mg/mL 02244290 Paladin Labs Inc.
Methadose methadone hydrochloride oral concentrate, 10 mg/mL 02394618 Mallinckrodt Canada ULC
Methadose methadone hydrochloride oral concentrate, 10 mg/mL 02394596 Mallinckrodt Canada ULC
Odan-Methadone* methadone hydrochloride oral concentrate, 10 mg/mL 02495872 Odan Laboratories Ltd.
Odan-Methadone* methadone hydrochloride oral concentrate, 10 mg/mL 02495880 Odan Laboratories Ltd.
Sandoz Methadone methadone hydrochloride oral concentrate, 10 mg/mL 02481979 Sandoz Canada Inc.

* Jamp Methadone Oral Concentrate and Odan-Methadone have been authorized for use in Canada since January 2020; as of the date of this communication, they are not marketed. 

Background information

Currently in Canada, Metadol-D, Methadose, and Sandoz Methadone are used for substitution treatment for opioid dependence in adults. Jamp Methadone Oral Concentrate and Odan-Methadone have been authorized for this use since January 2020; as of the date of this communication, they are not marketed. Methadone powder is also available to pharmacists to compound their own methadone solutions.

In March 2020, Health Canada issued a risk communication to inform healthcare professionals that it had received reports from patients and healthcare professionals that there may be variations in how patients respond to different methadone-containing products when used for opioid substitution treatment in opioid drug dependence.

Health Canada has reviewed the potential risk of lack of effect when switching between different methadone-containing products used to treat opioid dependence. The analysis included scientific and medical literature, Canadian and international information including case reports and engagement with Canadian healthcare professionals and patients, and what is known about the use of methadone both in Canada and internationally.

Despite widespread use of these products in Canada, only a small number of Canadian cases of lack of effect or drug withdrawal following methadone-containing product switch were received and assessed by Health Canada. Health Canada did not identify a pharmacological basis for the reported and observed differences in clinical response to different methadone-containing products. A specific sub-population at risk was also not identified. Canadian and international literature, as well as feedback from Canadian healthcare professionals, suggest that psychosocial factors may play a role and some patients do not tolerate methadone-containing product changes.

While the underlying cause has not been attributed to any specific problems with the drug itself, patients experiencing withdrawal symptoms when switching products may reinitiate or increase problematic substance use and risk quitting their treatment program, which can have a significant impact on their well-being, and the well-being of their families.

Who is affected

Information for consumers

Methadone is prescribed for use in patients requiring substitution treatment for opioid drug dependence. It can also be used as part of a treatment plan that includes social and psychological support. It is important that patients comply with their dosing schedule in order to maximize their treatment success. 

Some patients, after being switched from one methadone-containing product to another, may experience symptoms of opioid withdrawal. Patients taking these products who develop symptoms of opioid withdrawal should seek medical help. Symptoms may include rapid heart rate, feeling nervous or restless, swelling, nausea, vomiting, diarrhea, anxiety, shivering, cold and clammy skin, body aches, loss of appetite, and sweating.

Patients should contact their healthcare professional if they have concerns about how well their medication is working as adjustments to their dose may be required.

Information for healthcare professionals

Healthcare professionals are being advised that:

  • Patients may experience withdrawal symptoms after being switched from one methadone-containing product to another; these patients should be clinically managed and monitored regularly.
  • Dose adjustments may be necessary for some patients.
  • Withdrawal symptoms can lead to a failure to remain in treatment and subsequent problematic substance use, which can lead to serious harms.

Action taken by Health Canada

Health Canada will be working with the manufacturers to update the Canadian product information to warn of this potential safety issue.

Health Canada will continue to assess this safety issue on a regular basis through planned, ongoing reviews. Should new evidence emerge, Health Canada will update and communicate its recommendations.

Health Canada is communicating this important safety information to healthcare professionals and Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians Web Site. This communication will be further distributed through the MedEffect™ e-Notice email notification system as well as social media channels including LinkedIn and Twitter.

 

Report health or safety concerns

Health Canada’s ability to monitor the safety of marketed health products depends on healthcare professionals and consumers reporting adverse reactions and medical device incidents. Any changes in patient response, including withdrawal symptoms, or other serious or unexpected adverse reactions in patients receiving methadone should be reported to Health Canada.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

  • Calling toll-free at 1-866-234-2345; or
  • Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax.

For other health product inquiries related to this communication, contact Health Canada at:

Marketed Health Products Directorate
E-mail: mhpd-dpsc@canada.ca
Telephone: 613-954-6522
Fax: 613-952-7738