Resmetirom tablet 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).

Resmetirom is a partial agonist of thyroid hormone receptor-beta (THR-β). It produces 83.8% of the maximum response compared to triiodothyronine (T3), with an EC50 of 0.21 μM in an in vitro functional assay for THR-β activation. In the same assay for thyroid hormone receptor alpha (THR-α), it shows 48.6% efficacy relative to T3, with an EC50 of 3.74 pM. THR-β is the major thyroid hormone receptor in the liver, and its activation reduces intrahepatic triglyceride levels.

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

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

Resmetirom can be administered with or without food.

Effect of other drugs on Resmetirom: Strong or moderate CYP2C8 inhibitors: Concomitant use of Resmetirom with strong or moderate CYP2C8 inhibitors may increase the risk of adverse reactions. Use with strong CYP2C8 inhibitors (e.g., Gemfibrozil) is not recommended. If used with moderate CYP2C8 inhibitors (e.g., Clopidogrel), the dose of Resmetirom should be reduced as follows:

• Body weight <100 kg: 60 mg once daily
• Body weight >100 kg: 80 mg once daily

OATP1B1 and OATP1B3 inhibitors: Concomitant use may increase Resmetirom exposure and risk of adverse effects. Use with OATP1B1/OATP1B3 inhibitors (e.g., Cyclosporine) is not recommended.

Effect of Resmetirom on other drugs: Statins (Atorvastatin, Pravastatin, Rosuvastatin, Simvastatin): Resmetirom increases plasma levels of these statins, increasing risk of statin-related adverse reactions. Dose adjustment is recommended:

• Rosuvastatin and Simvastatin: maximum 20 mg/day
• Pravastatin and Atorvastatin: maximum 40 mg/day

CYP2C8 substrates: Resmetirom increases exposure of CYP2C8 substrates (e.g., Pioglitazone), increasing risk of adverse reactions. Patients should be closely monitored when co-administered.

Common side effects include: diarrhea, nausea, vomiting, abdominal pain, dizziness, pruritus, and constipation.

Pregnancy: No adequate data are available on use in pregnant women to determine risk of birth defects, miscarriage, or other adverse outcomes.

Lactation: No information is available regarding presence in human milk or effects on breastfed infants. The benefits of breastfeeding should be weighed against maternal need for Resmetirom and any potential risk to the infant.

Hepatotoxicity: Liver injury has been reported. Liver function tests should be monitored during treatment. If hepatotoxicity is suspected, discontinue Resmetirom. Restarting should be considered only after risk–benefit evaluation.

Gallbladder-related reactions: Cholelithiasis, acute cholecystitis, and gallstone pancreatitis have been reported. If suspected, perform diagnostic evaluation and manage appropriately. Interrupt treatment if an acute event occurs.

Statin interaction: Increased statin exposure may increase risk of adverse reactions; dose adjustment is recommended.

Pediatric use: Safety and efficacy have not been established.

Geriatric use: Similar efficacy, but higher incidence of adverse reactions may occur in patients ≥65 years.

Renal impairment: No dose adjustment required in mild to moderate renal impairment. Not studied in severe renal impairment.

Hepatic impairment: Avoid use in decompensated cirrhosis or moderate–severe hepatic impairment (Child-Pugh B or C). No dose adjustment needed in mild impairment (Child-Pugh A).

Store below 30°C in a cool, dry place. Protect from light. Keep out of reach of children.