Other safety alerts
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| Canada: Summary Safety Review: Gadolinium-based Contrast Agents: Assessing the potential risk of serious adverse reactions, including seizures, encephalopathy, coma and death, with intrathecal use |
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Product
Gadolinium-based contrast agents (Dotarem [gadoterate meglumine], Gadovist 1.0 [gadobutrol], Magnevist [gadopentetate dimeglumine], MultiHance [gadobenate dimeglumine], Omniscan [gadodiamide], Primovist [gadoxetate disodium] and ProHance [gadoteridol]) (GBCAs)
Potential Safety Issue
Serious adverse reactions, including seizures, encephalopathy (brain dysfunction), coma and death, with intrathecal (injection into the spinal canal) use
Key Messages
- Health Canada’s review found a possible link between the intrathecal use of GBCAs and serious adverse reactions, including seizures, encephalopathy, coma and death.
- Health Canada is working with manufacturers to update the product safety information in the Canadian product monograph (CPM) for all GBCAs to include the risk of serious adverse reactions, including seizures, encephalopathy, coma and death, with off label intrathecal use.
Overview
Health Canada reviewed the potential risk of serious adverse reactions, including seizures, encephalopathy, coma and death with the intrathecal use of GBCAs. The safety review was triggered by a labelling update in the United States for all GBCAs.
Gadolinium-based contrast agents are not authorized in Canada for intrathecal use. However, Health Canada is aware that they have been used off-label for this route of administration.
Use in Canada
- Gadolinium-based contrast agents are authorized for use in magnetic resonance imaging (MRI) to make it easier to view certain body tissues and to help with the diagnosis of various conditions. They are authorized to be given into a vein (intravenously).
- Gadolinium-based contrast agents have been marketed in Canada for over 30 years. There are 7 GBCAs currently marketed under the following brand names: Dotarem, Gadovist 1.0, Magnevist, MultiHance, Omniscan, Primovist and ProHance. A generic version of Gadovist 1.0 is also available.
- From 2019 to 2024, approximately 2.5 million patients in Canada were given GBCAs. However, information on intrathecal usage is not available.
Safety Review Findings
- Health Canada reviewed the available information from the Canada Vigilance database, the scientific literature, and clinical experts.
- Health Canada reviewed 22 cases (1 Canadian and 21 international) of serious adverse reactions, including seizures, encephalopathy, coma and death, in patients who were administered GBCAs intrathecally. Of the 22 cases, 18 (1 Canadian and 17 international) were found to be possibly linked, including 11 from the published literature. The remaining 4 cases could not be assessed due to missing clinical information.
- The dose given was reported in 15 of the 18 cases that were possibly linked to the intrathecal use of GCBAs, and ranged from 1.5 mmol to 12 mmol (median dose 3 mmol).
- All 18 cases that were possibly linked to the intrathecal use of GCBAs involved adult patients. In 17 (1 Canadian) of those cases, the patients recovered or were recovering. A death occurred in the remaining case.
- Health Canada also reviewed the findings from 28 published studies. There were no reports of seizures, encephalopathy, coma or death in patients administered GBCAs intrathecally.
Conclusions and Actions
- Health Canada’s review of the available information found a possible link between the intrathecal use of GBCAs and serious adverse reactions, including seizures, encephalopathy, coma and death.
- Health Canada is working with manufacturers to update the CPM for all GBCAs to include the risk of serious adverse reactions, including seizures, encephalopathy, coma and death, with off label intrathecal use.
- Health Canada will continue to monitor safety information involving GBCAs, 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/SSR1747762855840
In Hong Kong, there are registered pharmaceutical products which belong to gadolinium-based contrast agents containing meglumine gadoterate (10 products), gadobutrol (2 products), gadobenic acid (as meglumine gadobenate or gadobenate dimeglumine) (1 product), sodium gadoxetate (gadoxetate disodium) (1 product). All products are prescription-only medicines and are indicated for intravenous administration only.
So far, according to available information, the Department of Health (DH) has not received case of adverse drug reaction with regard to intrathecal use of the above gadolinium-based contrast agents. In light of the above Health Canada’s announcement, letters to inform local healthcare professionals will be issued, and the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Friday, Jun 27, 2025
Issued at HKT 18:00
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