Summary Safety Review - HMG-CoA Reductase Inhibitors (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin) - Statins - Assessing the Potential Risk of Myasthenia Gravis, Including Ocular Myasthenia

HMG-CoA reductase inhibitors (atorvastatin-, fluvastatin-, lovastatin-, pravastatin-, rosuvastatin- and simvastatin-containing products), more commonly known as statins

Myasthenia gravis, including ocular myasthenia (a neuromuscular condition that causes weakness of the voluntary muscles of the body, including those that control the eyes and eyelids)

• Health Canada’s review concluded that there is a possible link between statins and the risk of myasthenia gravis, including ocular myasthenia, and that this is a class-effect.

• Health Canada will work with the manufacturers to update the product safety information in the Canadian product monograph (CPM) for statin products that are currently not labelled with the risk of myasthenia gravis, including ocular myasthenia.

Health Canada reviewed the potential risk of myasthenia gravis, including ocular myasthenia, with the use of statins. The safety review was triggered by a labelling update for all statin products by the European Medicines Agency.

At the time of this review, the manufacturers of 2 Canadian statin products, Crestor (rosuvastatin) and Zocor (simvastatin), initiated a labelling update to include the risk of myasthenia gravis, including ocular myasthenia, in their respective CPMs. The purpose of this review was to determine whether this risk is associated with all statin products, warranting labelling updates across the drug class.

• Statins are prescription drugs authorized for sale in Canada, to be used along with diet, to lower cholesterol and triglyceride (fat) levels in the blood, and to reduce the risk of heart attack or stroke in patients with risk factors for heart problems.

• Statins have been marketed in Canada since 1995. There are currently 6 statins available in Canada (rosuvastatin, atorvastatin, simvastatin, fluvastatin, lovastatin, pravastatin) as single-ingredient and fixed-combination oral tablets and oral capsules under different brand names and generic versions.

• Approximately 282 million prescriptions for statins were dispensed by Canadian retail pharmacies between 2018 and 2023.

• Health Canada reviewed the available information provided by manufacturers, and from searches of the Canada Vigilance database^a, international databases and the scientific literature.

• Health Canada reviewed 31 cases (2 Canadian and 29 international) of myasthenia gravis and/or ocular myasthenia in patients taking statins. Of the 31 cases, 27 (1 Canadian) were found to be possibly linked to the use of statins, 1 was unlikely to be linked and 3 (1 Canadian) could not be assessed due to missing information. Of the possible cases, 3 had recurrence of symptoms of myasthenia gravis and/or ocular myasthenia when treated with different statins, which suggests a drug class-effect for this risk.

• Health Canada also reviewed 4 studies published in the scientific literature^1-4. Despite limitations, the studies provided evidence supporting a link between statins and worsening myasthenia gravis and/or ocular myasthenia. Evidence of a link between statins and new occurrence of myasthenia gravis and/or ocular myasthenia in published studies was limited; however, published case reports supported a possible link.

• Health Canada’s review found a possible link between statins and the risk of myasthenia gravis, including ocular myasthenia, and that this is a class-effect.

• Health Canada will work with the manufacturers to include the risk of myasthenia gravis, including ocular myasthenia, in the CPM for statin products that do not currently include this risk.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of statins, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving statins, 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 if and when any new health risks are identified.

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 statins both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Gras‐Champel V, Batteux B, Masmoudi K, Liabeuf S. Statin‐induced myasthenia: A disproportionality analysis of the WHO’s VigiBase pharmacovigilance database. Muscle & Nerve. 2019;60(4):382-386. Accessed October 23, 2024. https://doi.org/10.1002/mus.26637

2. Oh SJ, Dhall R, Young A, Morgan MB, Lu L, Claussen GC. Statins may aggravate myasthenia gravis. Muscle & Nerve. 2008;38(3):1101-1107. Accessed October 23, 2024. https://doi.org/10.1002/mus.21074

3. Virgo J, Wong S, Rantell K, Plant G. Statins Can Cause Myasthenia Gravis: Fact or Fiction? Journal of Neurology, Neurosurgery & Psychiatry. 2013;84(11):e2.126-e2. Accessed October 23, 2024. https://doi.org/10.1136/jnnp-2013-306573.211

4. Goldobin V.; Klocheva E.; Alibekov A. Effect of statin use on severity of late onset myasthenia gravis. European Journal of Neurology. 2022;29

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