Summary Safety Review - Oral prednisone and prednisolone (glucocorticoids) - Assessing the potential risk of a serious complication called scleroderma renal crisis in patients with systemic sclerosis

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: 2018-08-07

Product

prednisone and prednisolone (glucocorticoids) for oral use

Potential Safety Issue

Serious complication called scleroderma renal crisis (SRC) in patients with systemic sclerosis

Key Messages

  • Prednisone and prednisolone are prescription drugs authorized for sale in Canada for a number of uses, including treating allergies and inflammation. They work by decreasing the body's reaction to some diseases and by reducing inflammation.
  • Health Canada reviewed the potential risk of scleroderma renal crisis (SRC) with the use of oral prednisone and prednisolone products in patients with systemic sclerosis. The review was triggered after the European Medicines Agency (EMA) updated the product safety information for oral and injectable prednisone and prednisolone products on July 6, 2017, to include this risk.
  • Health Canada's review concluded that there may be a link between the use of oral prednisone and prednisolone, especially at higher doses, and the risk of SRC in patients with systemic sclerosis.
  • Health Canada will be working with the manufacturers to update the Canadian product safety information for oral prednisone and prednisolone products to inform healthcare professionals and patients about this risk.

Overview

  • Systemic sclerosis (also known as scleroderma) is a rare disease involving an abnormal response from the body's immune system. The disease causes changes in the texture and appearance of the skin, and frequently involves the internal organs.
  • Scleroderma renal crisis is a life-threatening complication of systemic sclerosis that frequently involves severe high blood pressure and declining function of the kidneys.

Use in Canada

  • Prednisone and prednisolone are available in Canada in a variety of forms and combinations. The current review focused only on prednisone and prednisolone products for oral use since this route delivers higher doses of the product throughout the body. Injectable prednisone and prednisolone are not marketed in Canada.
  • Oral prednisone and prednisolone products have been marketed in Canada since the 1950s.
  • In 2017, more than 3.2 million prescriptions of these products were filled in Canada. Only a small percentage of the total was for use in patients with systemic sclerosis.

Safety Review Findings

  • At the time of the review, Health Canada had received 2 Canadian reportsa of SRC related to the use of prednisone (none for prednisolone). In both reports, there was a possible link found between SRC and the use of prednisone. No Canadian deaths were reported.
  • This review also looked at 6 published international reports of SRC related to the use of prednisone (1 report) and prednisolone (5 reports). In all 6 reports, there was a possible link found between SRC and the use of prednisone or prednisolone, especially at higher doses.
  • Of the 6 international reports, 3 involved death. A possible link between death and the use of prednisolone was found in 1 of these cases. The remaining 2 cases could not be assessed as there was not enough information.
  • Seven out of 8 possible cases of prednisone and prednisolone associated with SRC had other factors present (i.e. medical conditions, other medications) that could have caused SRC.
  • A review of the scientific literature found 6 published studies and 3 review articles that supported an increased risk of SRC in patients with systemic sclerosis treated with prednisone or prednisolone, especially at higher doses.
  • The EMA updated the product safety information of oral and injectable prednisone and prednisolone products on July 6, 2017, to include safety information specific to the risk of SRC in patients with systemic sclerosis.
  • The EMA is the only known major foreign regulator to have taken action regarding this risk with these products.

Conclusions and actions

  • Health Canada's review of the available information has concluded that there may be a link between the use of oral prednisone and prednisolone products, especially at higher doses, and SRC in patients with systemic sclerosis.
  • Health Canada will be working with the manufacturers to update the Canadian product safety information for oral prednisone and prednisolone products to inform about this risk.
  • Health Canada will continue to monitor safety information involving oral prednisone and prednisolone products, 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 information, and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

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

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