Summary Safety Review - Proton Pump Inhibitors - Assessing the Potential Risk of Clostridium difficile Infection

May 6, 2016

Product

Proton pump inhibitors

Potential Safety Issue

Clostridium difficile infection

Key Messages

• Proton pump inhibitors are drugs that are used to reduce stomach acid to treat heartburn and ulcers on the lining of the stomach/intestines.
• Health Canada's review on the potential risk of Clostridium difficile infection with proton pump inhibitor use was carried out to assess new evidence since completion of the previous review in 2012. Following the 2012 review, Health Canada issued an Advisory to inform Canadians of the potential contribution of proton pump inhibitors to the overall risk of Clostridium difficile infection.
• The current Health Canada review concluded that the evidence is limited to establish that proton pump inhibitors cause Clostridium difficile infection. The Canadian prescribing information for all proton pump inhibitors already reflects the observation that patients using these drugs are slightly more likely to develop Clostridium difficile infections. It will be updated to include additional details on the risk of Clostridium difficile infection and to encourage optimal use of proton pump inhibitors.

Overview

This safety review was carried out to look at new information in the scientific literature that has emerged since the completion of a previous review in 2012 about the risk of Clostridium difficile infection with proton pump inhibitor use. Clostridium difficile infection ranges from mild diarrhea to life-threatening multi-organ failure, especially in elderly patients with other pre-existing conditions. This safety issue has been monitored by Health Canada since 2009, and in 2010, the prescribing information documents for all proton pump inhibitors were updated to inform Canadians about the potential role of these drugs as a risk factor for Clostridium difficile infection. In 2012, Health Canada carried out a follow-up assessment and posted an Advisory to inform Canadians of the potential contribution of proton pump inhibitors to the overall risk of Clostridium difficile infection.

Use in Canada

• Proton pump inhibitors are drugs that are used to reduce stomach acid in the treatment of heartburn and stomach/intestinal ulcers.
• There are six proton pump inhibitors available in Canada: omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet) and dexlansoprazole (Dexilant). There are also some generic versions of these drugs sold in Canada.
• Most proton pump inhibitors are available by prescription only, however some omeprazole products are available without a prescription (e.g., Olex).

Safety Review Findings

• At the time of this review, Health Canada had received a total of 10 reports of Clostridium difficile infection in patients who were using proton pump inhibitors. Of these reports, 2 were received since the previous review in 2012.
• A search in the World Health Organization's database at the time of this review found 233 reports of Clostridium difficile infection in patients who were using proton pump inhibitors.
• Given the widespread use of these drugs in Canada and internationally, the number of reports is considered to be low.
• Scientific literature reports have described a potential link between proton pump inhibitor use and Clostridium difficile infection and/or recurrence. However, patients included in these studies had other known risk factors that could have contributed to the development of Clostridium difficile infection.

Conclusions and Actions

• Health Canada's safety reviews concluded that the evidence was too limited to establish that the use of proton pump inhibitors causes Clostridium difficile infection.
• Currently, the prescribing information for proton pump inhibitors reflects the observation that patients using proton pump inhibitors are slightly more likely to develop Clostridium difficile infections. Since the potential link has not been ruled out, the prescribing information will be updated to provide more information on various risk factors.
• The prescribing information for proton pump inhibitors will also be updated to remind healthcare professionals and patients that these drugs should be used at the lowest dose and for the shortest duration appropriate to the condition being treated.
• Health Canada continues to monitor side effect information involving proton pump inhibitors, 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 is known about the use of this drug both in Canada and internationally.

The Canadian Agency for Drugs and Technologies in Health carried out a review in 2014-2015 to look at the link between proton pump inhibitor use and Clostridium difficile infection. The findings of this review were similar to those from Health Canada's safety review on this issue.

For additional information, contact the Marketed Health Products Directorate.