Resmetirom is a partial agonist of the thyroid hormone receptor-beta (THR-β). 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. Resmetirom works to improve lipid metabolism (eg, reduces intrahepatic triglycerides and free fatty acids) and reduces inflammation in the liver. This helps to address drivers of disease progression, reduce liver damage, and improve liver health.

Resmetirom is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

Avoid use of Resmetiorm in patients with decompensated cirrhosis.

The recommended dosage of Resmetirom is based on actual body weight. For patients weighing:

• <100 kg, the recommended dosage is 80 mg orally once daily.
• ≥100 kg, the recommended dosage is 100 mg orally once daily.

Dosage Modifications for CYP2C8 Inhibitors

Concomitant use of resmetiorm with strong CYP2C8 inhibitors (e.g., gemfibrozil) is not recommended. If Resmetiorm is used concomitantly with a moderate CYP2C8 inhibitor (e.g., clopidogrel), reduce the dosage of resmetiorm.

If <100 kg: reduce the dosage of Resmetiorm to 60 mg once daily
If ≥100 kg: reduce the dosage of Resmetiorm to 80 mg once daily

Administer Resmetirom with or without food.

None

• Hepatotoxicity : Hepatotoxicity has been observed with use of Resmetirom. 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.

• 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.

Statins (Atorvastatin, Pravastatin, Rosuvastatin, or Simvastatin)

Resmetirom increased plasma concentrations of some statins which may increase the risk of adverse reactions related to these drugs. Rosuvastatin and simvastatin: Limit daily statin dosage to 20 mg. Pravastatin and atorvastatin: Limit daily statin dosage to 40 mg.

CYP2C8 Substrates

Resmetirom is a weak CYP2C8 inhibitor. Resmetirom increases exposure of CYP2C8], which may increase the risk of adverse reactions related to these substrates. Monitor patients more frequently for substrate-related adverse reactions if Resmetirom is co-administered with CYP2C8 substrates where minimal concentration changes may lead to serious adverse reactions.

Strong or Moderate CYP2C8 Inhibitors

Resmetirom is a CYP2C8 substrate. Concomitant use with a strong or moderate CYP2C8 inhibitor can increase Resmetirom Cmax and AUC, which may increase the risk of Resmetirom adverse reactions. Concomitant use of Resmetirom with strong CYP2C8 inhibitors (e.g., gemfibrozil) is not recommended. Reduce Resmetirom dosage if used concomitantly with a moderate CYP2C8 inhibitor (e.g., clopidogrel)

Organic Anion-Transporting Polypeptides (OATP) 1B1 and OATP1B3 Inhibitors

Resmetirom is an OATP1B1 and OATP1B3 substrate. Concomitant use with OATP1B1 and OATP1B3 inhibitors may increase Resmetirom Cmax and AUC, which may increase the risk of Resmetirom adverse reactions. Concomitant use of Resmetirom with OATP1B1 or OATP1B3 inhibitors (e.g., cyclosporine) is not recommended.

Pregnancy : There are no available data on Resmetirom use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation: There is no information regarding the presence of Resmetirom in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Resmetirom and any potential adverse effects on the breastfed infant from Resmetirom or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness of Resmetirom have not been established in pediatric patients.

Geriatric Use : Numerically higher incidence of adverse reactions has been observed in patients ≥65 years of age compared to younger adult patients.

Hepatic Impairment: Avoid use in patients with decompensated cirrhosis (consistent with moderate to severe hepatic impairment). Moderate or severe hepatic impairment (Child-Pugh Class B or C) may increase the risk of adverse reactions.

The safety and effectiveness have not been established in patients with cirrhosis.

Renal Impairment: Resmetirom has not been studied in patients with severe renal impairment.

Store at 20 °C to 25°C temperature in a dry place. Protect from light & moisture.

Medicine: Keep out of reach of children