Resmetirom

REZDIFFRA ® is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitations of Use Avoid use of REZDIFFRA in patients with decompensated cirrhosis.

Resmetirom is a partial agonist of the thyroid hormone receptor-beta (THR-β). Resmetirom produced 83.8% of the maximum response compared to triiodothyronine (T3), with an EC 50 of 0.21 µM in an in vitro functional assay for THR-β activation. The same functional assay for thyroid hormone receptor-alpha (THR-α) agonism showed 48.6% efficacy for resmetirom relative to T3, with an EC 50 of 3.74 µM. THR-β is the major form of THR in the liver, and stimulation of THR-β in the liver reduces intrahepatic triglycerides, whereas actions of thyroid hormone outside the liver, including in heart and bone, are largely mediated through THR-α.

The recommended dosage of REZDIFFRA is based on actual body weight. For patients weighing: o <100 kg, the recommended dosage is 80 mg orally once daily. o ≥100 kg, the recommended dosage is 100 mg orally once daily. Administer REZDIFFRA with or without food. Swallow REZDIFFRA tablets whole, do not split, crush, or chew tablets. See full prescribing information for REZDIFFRA dosage modifications with concomitant use of moderate CYP2C8 inhibitors.

None. None.

Hepatotoxicity: Monitor patients during treatment with REZDIFFRA for elevations in liver tests and for the development of liver-related adverse reactions. Discontinue REZDIFFRA and continue to monitor the patient if hepatotoxicity is suspected. Gallbladder-Related Adverse Reactions: Cholelithiasis and cholecystitis were observed more often in REZDIFFRA-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an acute gallbladder event such as acute cholecystitis is suspected, interrupt REZDIFFRA treatment until the event is resolved.

The following clinically significant adverse reactions are described elsewhere in labeling: Hepatotoxicity Gallbladder-Related Adverse Reactions The most common adverse reactions with REZDIFFRA (reported in at least 5% of patients and higher compared to placebo) are: diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness.

Strong or Moderate CYP2C8 Inhibitors: Concomitant use not recommended (strong inhibitor [e.g., gemfibrozil]), or reduce REZDIFFRA dosage (moderate inhibitor [e.g., clopidogrel]). Atorvastatin, Pravastatin, Rosuvastatin and Simvastatin: Limit the daily dosage of the statin as recommended. CYP2C8 Substrates: Monitor patients more frequently for substrate-related adverse reactions.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).