Summary Safety Review - Celecoxib (CELEBREX and generics) - Assessing the Risk of Serious Heart and Stroke Side Effects at High Doses Relative to Other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
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: 2016-04-11
Product
Celecoxib (Celebrex and generics)
Potential Safety Issue
Risk of serious heart and stroke side effects at high doses relative to other non-steroidal anti-inflammatory drugs (NSAIDs)
Overview
Use in Canada
- Celecoxib is indicated for relief of symptoms linked with:
- Osteoarthritis, a disease linked with swelling and pain of the joints.
- Adult rheumatoid arthritis, an autoimmune disease causing damage and inflammation in the joints.
- Ankylosing spondylitis, a disease affecting the joints of the spine.
- Celecoxib is also indicated for the short-term (7 days) management of moderate to severe acute pain in adults in conditions such as the following:
- Musculoskeletal and/or soft tissue trauma including sprains
- Postoperative orthopaedic, and
- Pain following dental extraction
- Health Canada estimates that the number of prescriptions for celecoxib is approximately 2.6 million per year.
Safety Review Findings
- At the time of the review, Health Canada had received 39 Canadian adverse reaction reports where death due to heart and stroke related side effects were linked with celecoxib use.
- Health Canada's review of scientific and medical literature identified many studies. Overall, these studies concluded that there is an increased risk of serious heart and stroke related side effects linked with the use of celecoxib at doses greater than 200 mg per day. This risk may be higher in patients taking the drug for longer than 18 months.
- Based on a review of the available data, a relative ranking of NSAIDs in terms of their cardiovascular safety could not be carried out at this time. However, there is currently an ongoing clinical trial being carried out to study the relative cardiovascular safety profile of different doses of celecoxib, ibuprofen and naproxen.
Conclusions and actions
- Health Canada's review of the evidence supports the conclusion that celecoxib (at doses of higher than 200 mg per day) may be linked with an increased risk of serious heart and stroke related side effects and this risk is similar to the risks linked with the use of high doses of diclofenac (≥150 mg per day) or ibuprofen (≥2400 mg per day).
- In order to further reduce the risks linked with celecoxib, additional information is being added to the prescribing information for celecoxib which includes:
- Celecoxib, particularly at doses greater than 200 mg per day, may be linked with an increased risk of heart and stroke related adverse events and this risk should be considered when prescribing celecoxib.
- Recommending a lower dose of the medication (200 mg or less per day), especially in patients with pre-existing or risk factors for heart disease
- Health Canada has determined that the overall benefits of celecoxib continue to outweigh the risks, when used as recommended. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
- Health Canada will continue to monitor side effect information involving celecoxib, 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.
Additional information
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what are known about the use of this drug both in Canada and internationally. For additional information, contact the Marketed Health Products Directorate.
References
- Bhala N, Emberson J, Merhi A, et al. Coxib and traditional NSAID trialist CNT Collaboration group: Vascular and upper gastrointestinal effects on non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382:769-79.