Summary Safety Review - Tagrisso (osimertinib) - Assessing the Potential Risk of Rhabdomyolysis and Other Myopathy-related Events

Tagrisso (osimertinib)

Rhabdomyolysis (muscle breakdown) and other myopathy-related events (muscle disorders), including myositis (muscle inflammation) and elevated creatine phosphokinase (CPK), an enzyme that indicates the presence of muscle breakdown

• Tagrisso (osimertinib) is authorized for sale in Canada to treat adults with a specific type of lung cancer.

• Health Canada reviewed the potential risks of rhabdomyolysis and other myopathy-related events with the use of Tagrisso. The safety review was triggered by the United States Food and Drug Administration’s (U.S. FDA) investigation of the risk of rhabdomyolysis and by published cases of myositis and elevated CPK with the use of Tagrisso in the scientific literature^1,2,3.

• Health Canada’s review of the available information found a possible link between the use of Tagrisso and the risk of rhabdomyolysis and other myopathy-related events, including myositis and elevated CPK.

• Health Canada is working with the manufacturer to update the product safety information in the Canadian product monograph (CPM) for Tagrisso with a warning about reported cases of rhabdomyolysis, myositis and elevated CPK. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Health Canada reviewed the potential risks of rhabdomyolysis and other myopathy-related events with the use of Tagrisso. The safety review was triggered by the U.S. FDA’s investigation of the risk of rhabdomyolysis and by published cases of myositis and elevated CPK with the use of Tagrisso in the scientific literature^1,2,3.

Myopathy is a general term referring to muscle disorders. Rhabdomyolysis, a rare and serious condition, is a severe form of myopathy with muscle break down and highly elevated CPK in the blood. The presence of muscle breakdown can be determined by measuring blood levels of CPK. Myositis refers to muscle inflammation.

• Tagrisso is a prescription drug authorized for sale in Canada to treat a specific type of lung cancer at various stages in adults.

• Osimertinib has been marketed in Canada since 2016. It is currently available as 40 mg and 80 mg oral tablets under the brand name Tagrisso.

• The estimated number of prescriptions of Tagrisso dispensed by Canadian retail pharmacies in 2022 was approximately 14,000.

• Health Canada reviewed information provided by the manufacturer, and from searches of the Canada Vigilance database^a and the published literature.

• At the time of the review, Health Canada had received 1 Canadian report of a myopathy-related event (elevated CPK) suspected to be associated with Tagrisso. The report did not contain sufficient details to allow assessment by Health Canada.

• Health Canada reviewed 22 international cases of rhabdomyolysis and/or other myopathy-related events (myositis and elevated CPK) in patients taking Tagrisso, including 7 from the published literature.

• Of the 22 cases reviewed:

  • 3 were found to be probably linked to the use of Tagrisso: 1 case of rhabdomyolysis, 1 of myositis and 1 of elevated CPK

  • 15 were found to be possibly linked: 3 cases of rhabdomyolysis, 4 of rhabdomyolysis and myositis, 4 of myositis and 4 with elevated CPK

  • 2 were unlikely to be linked, both with elevated CPK. One death was reported; however, it was determined that it was not related to the use of Tagrisso

  • 2 could not be assessed due to insufficient clinical information.

• Health Canada’s review of the available information found that there is a possible link between the use of Tagrisso and the risk of rhabdomyolysis and other myopathy-related events, including myositis and elevated CPK.

• Health Canada is working with the manufacturer to update the CPM for Tagrisso to include a warning about reported cases of rhabdomyolysis, myositis and elevated CPK.

• Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

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

• Health Canada will continue to monitor safety information involving Tagrisso, 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.

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

For additional information, contact the Marketed Health Products Directorate.

1. Crowley F, Fitzgerald B, Bhardwaj A, et al. Life threatening myositis in a patient with EGFR-mutated NSCLC on osimertinib: case report. JTO Clin Res Rep. 2022. Vol: 3. Page(s): 100260 DOI: https://doi.org/10.1016/j.jtocrr.2021.100260

2. Parafianowicz, P., R. Krishan, B. D. Beutler, R. X. Islam,T. Singh Myositis – A common but underreported adverse effect of osimertinib: Case series and review of the literature. Cancer Treatment and Research Communications 2020 25.

3. Sugimoto, H., S. Matsumoto, Y. Tsuji,K. Elevated serum creatine kinase levels due to osimertinib: A case report and review of the literature Journal of Oncology Pharmacy Practice 2022 28(2): 489-494.

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