Communication on risk of hepatotoxicity with concurrent use of Zelboraf® (vemurafenib) and ipilimumab

Roche would like to inform healthcare professionals of the risk of hepatotoxicity with concurrent use of Zelboraf® (vemurafenib) and ipilimumab. Severe (>5 x ULN) transaminase elevations were reported in 6 out of 10 metastatic melanoma patients who received concurrent Zelboraf® with ipilimumab in a Phase I trial. Moderate (>1.5 x ULN) to severe (3 x ULN) bilirubin elevations were also reported in 4 out of the 6 patients who had transaminase elevations. All patients with elevations of transaminase and/or bilirubin were asymptomatic and the findings were reversible within a short timeframe (4-20 days) upon study drug(s) discontinuation, dose reduction, and in some cases, with the administration of corticosteroids. Concurrent use of Zelboraf® with ipilimumab is not recommended. The mechanism of hepatotoxicity resulting from concurrent administration of ipilimumab and Zelboraf® is unknown. Please note that ipilimumab has not been approved for use in Singapore. The package insert for Zelboraf® will be updated to reflect the new safety information.