Summary Safety Review - ZELBORAF (vemurafenib) - Pancreatitis

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: 2015-02-12

Product

ZELBORAF (vemurafenib)

Potential Safety Issue

Pancreatitis (inflammation of the pancreas)

Key Messages

  • ZELBORAF is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma). It works by targeting proteins made from a mutated gene called "BRAF".
  • A safety review was initiated following the identification of cases of ZELBORAF-associated pancreatitis in ongoing clinical trials.
  • The Canadian prescribing information for ZELBORAF has been updated to include the risk of pancreatitis. Health Canada has also issued a communication to inform patients and healthcare professionals of this risk.

Overview

A safety review was initiated following the identification of 18 cases of ZELBORAF-associated pancreatitis in ongoing clinical trials. Among these cases, 7 involved sudden-onset (acute) pancreatitis.

Use in Canada

  • ZELBORAF slows down or stops the growth of cancer cells by targeting specific proteins.
  • ZELBORAF is used in adult patients to treat an aggressive type of skin cancer (unresectable or metastatic melanoma) that has a mutation in the BRAF gene and that cannot be removed by surgery or has spread to other parts of the body.
  • It was first marketed in Canada on March 3, 2012.

Safety Review Findings

  • ZELBORAF may affect the multiplication and growth (proliferation) of tissue in the pancreas, which could potentially lead to obstructive pancreatitis.
  • TAFINLAR, another BRAF-inhibitor, is labelled for pancreatitis.
  • A total of 61 reports of pancreatitis associated with the use of ZELBORAF were retrieved from different sources (pre-clinical studies, scientific literature, manufacturer's clinical and safety databases, Health Canada's Canada Vigilance Program, the World Health Organization database and Health Canada's Office of Clinical Trials)a. Health Canada received 2 reports through the Canada Vigilance Program.
  • In 10 of the 61 reports, ZELBORAF was deemed to have had a "possible" or "probable" connection in causing the pancreatitis.

Conclusions and actions

  • Evidence of an association between ZELBORAF and the occurrence of pancreatitis was found by Health Canada. This association may be due, in part, to the fact that the drug may stimulate the proliferation of cells leading to obstructive pancreatitis.
  • The Canadian prescribing information for ZELBORAF has been updated to include the risk of pancreatitis.
  • Health Canada has issued a communication to inform patients and healthcare professionals of the risk of pancreatitis associated with the use of ZELBORAF.

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.

For additional information, contact the Marketed Health Products Directorate.

Footnotes

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

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