Summary Safety Review - JAKAVI (ruxolitinib) - Assessing the potential risk of drug interactions with P-glycoprotein (P-gp) substrates (including rosuvastatin)

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: 2018-10-09

Product

Jakavi (ruxolitinib)

Potential Safety Issue

Drug interactions with P-glycoprotein (P-gp) substrates (e.g. rosuvastatin, digoxin and dabigatran)

Key Messages

  • Jakavi (ruxolitinib) is a prescription drug authorized for sale in Canada to treat adult patients with certain types of blood cancers.
  • Health Canada carried out a safety review after receiving information on a Canadian report of a suspected drug interaction between ruxolitinib and rosuvastatin leading to increased blood cholesterol levels. P-glycoprotein (P-gp) substrates, including rosuvastatin, are drugs that are transported by P-glycoprotein in the body. The review also looked at the potential for ruxolitinib to interact with other P-gp substrates.
  • Health Canada's review of the available information did not establish a link between the use of ruxolitinib and the risk of interactions with P-gp substrates. Health Canada will continue to monitor the safety of ruxolitinib and will take appropriate and timely action if and when any new health risks are identified.

Overview

Health Canada reviewed the potential risk of a drug interaction between ruxolitinib and rosuvastatin (a P-gp substrate) after receiving a Canadian report of a suspected interaction between these 2 drugs. The report included a description of a suspected mechanism of interaction, which prompted Health Canada to include other drugs known to utilize the same transport mechanism, known as P-gp, in the safety review. The current product information for ruxolitinib states that ruxolitinib has no effect on P-gp transporters, based on earlier laboratory studies.

Use in Canada

  • Ruxolitinib is a prescription drug used to treat adult patients with an enlarged spleen (splenomegaly) and to help control the symptoms caused by myelofibrosis, a rare form of blood cancer. It is also used to control the excess amount of red blood cells in certain patients with polycythemia vera, a type of blood cancer.
  • Ruxolitinib has been marketed in Canada since 2012 under the brand name Jakavi and is available as tablets taken by mouth.

Safety Review Findings

  • At the time of the review, Health Canada had received 1 Canadian reporta of increased blood cholesterol due to a potential interaction between ruxolitinib and rosuvastatin. The review of this case could not conclude whether ruxolitinib interacted with rosuvastatin and/or played a role in the increased blood cholesterol observed in the patient. This is because patients with polycythemia vera may develop higher blood cholesterol levels when their disease is being treated.
  • The review also looked at 2 articles in the published literature which did not suggest an interaction between ruxolitinib and other drugs that are known to be transported by P-gp (e.g. digoxin, dabigatran and cyclosporine).
  • Available evidence at the time of review suggested that an interaction between ruxolitinib and rosuvastatin was unlikely because ruxolitinib did not appear to inhibit P-gp at doses typically used in patient treatment. Neither rosuvastatin nor ruxolitinib appear to directly interact with P-gp transporters.

Conclusions and actions

  • Health Canada's review concluded that the available evidence does not suggest an interaction between ruxolinitib and rosuvastatin or other drugs that are transported by P-gp. Therefore, it is unlikely that any observed increase in blood cholesterol was due to a ruxolitinib interaction with rosuvastatin in the Canadian report. The safety information for these products is appropriate at this time.
  • Health Canada will continue to monitor safety information involving ruxolitinib, 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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