Resmetirom

Mechanism-of-action classes: Breast Cancer Resistance Protein Inhibitors; Cytochrome P450 2C8 Inhibitors; Organic Anion Transporting Polypeptide 1B1 Inhibitors; Organic Anion Transporting Polypeptide 1B3 Inhibitors; Thyroid Hormone Receptor Agonists; Thyroid Hormone Receptor beta Agonists.

• REZDIFFRA 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). This indication is approved under accelerated approval based on improvement of NASH and fibrosis [see Clinical Studies (14) ] .

• None. None.contraindicated

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 ( 2.1 ) See full prescribing information for REZDIFFRA dosage modifications with concomitant use of moderate CYP2C8 inhibitors. ( 2.2 ) 2.1 Recommended Dosage and Administration The recommended dosage of REZDIFFRA 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. Administer REZDIFFRA with or without food [see Clinical Pharmacology (12.3) ] . Swallow REZDIFFRA tablets whole; do not split, crush, or chew tablets. Advise patients that if a dose is missed, do not take the missed dose and resume with the next scheduled dose. 2.2 Dosage Modifications for CYP2C8 Inhibitors Concomitant use of REZDIFFRA with strong CYP2C8 inhibitors (e.g., gemfibrozil) is not recommended [see Drug Interactions (7.1) ] . If REZDIFFRA is used concomitantly with a moderate CYP2C8 inhibitor (e.g., clopidogrel) [see Drug Interactions (7.1) ] , reduce the dosage of REZDIFFRA: <100 kg, reduce the dosage of REZDIFFRA to 60 mg once daily. ≥100 kg, reduce the dosage of REZDIFFRA to 80 mg once daily.

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. (5.1) 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. (5.2) 5.1 Hepatotoxicity Hepatotoxicity has been observed with use of REZDIFFRA. One patient had normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) levels at baseline, who received REZDIFFRA 80 mg daily, developed substantial elevations of liver biochemistries that resolved when treatment was interrupted. After reinitiating REZDIFFRA, 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 REZDIFFRA without any therapeutic intervention.

The following clinically significant adverse reactions are described elsewhere in labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] Gallbladder-Related Adverse Reactions [see Warnings and Precautions (5.2) ] 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. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Madrigal Pharmaceuticals, Inc. at 1-800-905-0324 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of REZDIFFRA was evaluated in two randomized, double-blind, placebo-controlled trials that enrolled a total of 2019 patients. Trial 1 Trial 1 included patients who had noncirrhotic NASH with stages F2 and F3 fibrosis at eligibility (n=888) [see Clinical Studies (14) ] . Adverse Reactions Leading to Discontinuations The exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY) for treatment discontinuation due to any adverse reaction were higher in the REZDIFFRA dosage arms: 4 per 100 PY, 5 per 100 PY, and 8 per 100 PY in placebo, REZDIFFRA 80 mg once daily, and REZDIFFRA 100 mg once daily arms, respectively. Diarrhea and nausea were the most common causes of treatment discontinuation.

Hepatic Impairment: Avoid use of REZDIFFRA in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C). (8.7) 8.1 Pregnancy Risk Summary There are no available data on REZDIFFRA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus related to underlying NASH with liver fibrosis (see Clinical Considerations ). In animal reproduction studies, adverse effects on embryo-fetal development occurred in pregnant rabbits treated with resmetirom at 3.5 times the maximum recommended dose during organogenesis. These effects were associated with maternal toxicity, whereas no embryo-fetal effects were observed at lower dose levels with better tolerance in pregnant rabbits. No embryo-fetal developmental effects occurred in pregnant rats treated with resmetirom or the metabolite MGL-3623. A pre- and postnatal development study in rats with maternal dosing of resmetirom during organogenesis through lactation showed a decrease in birthweight and increased incidence of stillbirths and mortality (postnatal days 1-4) at 37 times the maximum recommended dose (see Data ) . These effects were associated with marked suppression of maternal T4, T3, and TSH levels.

• Mar 14, 2024NDANDA217785Madrigal

1. 1Diarrhoea26217%
2. 2Nausea23215%
3. 3Pruritus23015%
4. 4Alanine Aminotransferase Increased1288.4%
5. 5Aspartate Aminotransferase Increased1238.1%
6. 6Fatigue1147.5%
7. 7Abdominal Pain Upper1046.8%
8. 8Dizziness966.3%
9. 9Vomiting905.9%
10. 10Weight Decreased905.9%
11. 11Hepatic Cirrhosis714.7%
12. 12Abdominal Pain674.4%
13. 13Constipation644.2%
14. 14Hepatic Enzyme Increased644.2%
15. 15Rash624.1%

The 10 most recently updated of 20 ClinicalTrials.gov registrations naming Resmetirom as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)
  Completed · Phase 2 · Interventional · 116 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT03038022updated 2026-06-04
• A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)
  Active not recruiting · Phase 3 · Interventional · 845 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT05500222updated 2026-06-02
• A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis
  Active not recruiting · Phase 3 · Interventional · 1,759 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT03900429updated 2026-06-01
• Study to Evaluate Resmetirom in Post-Liver Transplant Patients With MASH
  Recruiting · Phase 2 · Interventional · 120 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT07335601updated 2026-05-28
• A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)
  Active not recruiting · Phase 3 · Interventional · 810 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT04951219updated 2026-05-27
• A Study to Evaluate the Use of Resmetirom in Participants With MASLD and HIV
  Recruiting · Phase 2 · Interventional · 120 enrolled · Naga P. Chalasani
  NCT07143968updated 2026-05-06
• Rezdiffra Pregnancy and Lactation Registry
  Recruiting · Observational · 10 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT07541469updated 2026-04-21
• A Drug-Drug Interaction Study of Denifanstat and Resmetirom in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 40 enrolled · Sagimet Biosciences Inc.
  NCT07216313updated 2026-01-23
• Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH)
  Completed · Phase 2 · Interventional · 125 enrolled · Madrigal Pharmaceuticals, Inc.
  NCT02912260updated 2025-12-23
• Resmiterom Efficacy & Safety in Patients With MASH
  Recruiting · Phase 4 · Interventional · 165 enrolled · Nabiqasim Industries (Pvt) Ltd
  NCT07249788updated 2025-12-03

Frequently asked questions

How does Resmetirom work?

Mechanism-of-action classes: Breast Cancer Resistance Protein Inhibitors; Cytochrome P450 2C8 Inhibitors; Organic Anion Transporting Polypeptide 1B1 Inhibitors; Organic Anion Transporting Polypeptide 1B3 Inhibitors; Thyroid Hormone Receptor Agonists; Thyroid Hormone Receptor beta Agonists.

What is Resmetirom used for?

According to FDA labeling, Resmetirom carries indications including: REZDIFFRA 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). This indication is approved under accelerated approval based on improvement of NASH and fibrosis [see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Resmetirom?

Resmetirom is classified as Liver therapy, Thyroid Hormone Receptor beta Agonist, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2C8 Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, Thyroid Hormone Receptor Agonists, Thyroid Hormone Receptor beta Agonists, Lipid Metabolism Alteration.

What are the brand names for Resmetirom?

Resmetirom is marketed under brand names including Rezdiffra.

What are the contraindications for Resmetirom?

Resmetirom labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.