Adverse reactions of Resmetirom

1 Hepatotoxicity  

Hepatotoxicity has been observed with use of Resmetirom. One patient had normal alanine  aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at baseline,  who received Resmetirom 80 mg daily, developed substantial elevations of liver biochemistries that  resolved when treatment was interrupted. After reinitiating Resmetirom, the patient had elevations of  ALT, AST, and TB. Peak values observed were 58 x upper limit of normal (ULN) for ALT, 66 x ULN  for AST, 15 x ULN for TB, with no elevation of alkaline phosphatase (ALP). Elevations in liver  enzymes were accompanied by elevations in immunoglobulin G levels, suggesting drug-induced  autoimmune-like hepatitis (DI-ALH). The liver tests returned to baseline following hospitalization and  discontinuation of Resmetirom without any therapeutic intervention.

Monitor patients during treatment with Resmetirom for elevations in liver tests and for the  development of liver-related adverse reactions. Monitor for symptoms and signs of hepatotoxicity  (e.g., fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, and/or  eosinophilia [>5%]). If hepatotoxicity is suspected, discontinue Resmetirom and continue to monitor  the patient. If laboratory values return to baseline, weigh the potential risks against the benefits of  restarting Resmetirom. If laboratory values do not return to baseline, consider DI-ALH or autoimmune  liver disease in the evaluation of elevations in liver tests.

2 Gallbladder-Related Adverse Reactions  

In clinical trials, cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone) were  observed more often in Resmetirom-treated patients than in placebo-treated patients. If cholelithiasis  is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an  acute gallbladder event is suspected, interrupt Resmetirom treatment until the event is resolved.

FDA，2024.03