Precautions of Sotorasib

1.Hepatotoxicity 

Sotorasib can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among  357 patients who received Sotorasib in CodeBreaK 100, hepatotoxicity occurred  in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received Sotorasib had increased  alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were  Grade 4. The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3 to 42). Increased ALT/AST  leading to dose interruption or reduction occurred in 7% of patients. Sotorasib was discontinued due to  increased ALT/AST in 2.0% of patients. In addition to dose interruption or reduction, 5% of patients received  corticosteroids for the treatment of hepatotoxicity.  

Monitor liver function tests (ALT, AST, and total bilirubin) prior to the start of Sotorasib, every 3 weeks for the  first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who  develop transaminase and/or bilirubin elevations. Withhold, dose reduce or permanently discontinue Sotorasib  based on severity of adverse reaction.  

2.Interstitial Lung Disease (ILD)/Pneumonitis 

Sotorasib can cause ILD/pneumonitis that can be fatal. Among 357 patients who received Sotorasib in  CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were  Grade 3 or 4 at onset, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 2 weeks  (range: 2 to 18 weeks). Sotorasib was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor  patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever).  Immediately withhold Sotorasib in patients with suspected ILD/pneumonitis and permanently discontinue  Sotorasib if no other potential causes of ILD/pneumonitis are identified.

from FDA，2023.04