Safety Alerts
Risk of pancreatitis associated with vemurafenib
Audiences
Healthcare professional
Industry member
Product type
Therapeutic Products
30 September 2015
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Vemurafenib (Zelboraf®, Roche Singapore Pte Ltd) is a low molecular weight inhibitor of BRAF serine-threonine kinase. It has been registered locally since February 2013 for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This article highlights the overseas cases of pancreatitis that have been reported with the use of vemurafenib.
Review by overseas regulatory agencies
a) European Medicines Agency (EMA)
A signal relating to a possible association with vemurafenib in nine cases of pancreatitis retrieved from the EudraVigilance database was identified by the EMA during its routine signal detection activities. During its meeting in September 2012, EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) agreed that preliminary analysis of the nine cases provided sufficient information to warrant further analysis of the data.1 Further to two cumulative reviews conducted by the company in 2013 and 2014, the European labelling for Zelboraf® was updated in 2015 to add the adverse reaction of pancreatitis reported with a frequency of uncommon (i.e. occurring in ≥ 1/1,000 to < 1/100 patients).2
b) Health Canada
In February 2015, Health Canada concluded that there is evidence of an association between vemurafenib and the occurrence of pancreatitis, which may be due, in part, to the fact that the drug may stimulate the proliferation of cells leading to obstructive pancreatitis.3 The safety review was initiated following identification of 18 cases of vemurafenib-associated pancreatitis (including seven cases of acute pancreatitis) in ongoing clinical trials. A total of 61 reports of pancreatitis were retrieved from different sources, including scientific literature, the company’s clinical and safety databases, the World Health Organisation database, and Health Canada’s Vigilance Programme. The association of pancreatitis with use of vemurafenib was assessed to be “possible” or “probable” in 10 of the 61 reports. The Canadian labelling for Zelboraf® was subsequently updated to include the risk of pancreatitis.
Local situation
To date, HSA has not received any adverse reaction report of pancreatitis associated with vemurafenib. The local package insert (PI) for Zelboraf® currently lists pancreatitis as an uncommon adverse drug reaction. In view of overseas safety signals, the local PI has been strengthened to include information on patient monitoring and detection of pancreatitis.
HSA’s advisory
Healthcare professionals are advised to remain vigilant to the possible signs and symptoms of pancreatitis in patients who are prescribed vemurafenib, and to consider the possibility of pancreatitis in the event of unexplained abdominal pain.