Version July 2025
Noncirrhotic metabolic dysfunction–associated steatotic liver disease:
<100 kg (actual body weight): Oral: 80 mg once daily.
≥100 kg (actual body weight): Oral: 100 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate kidney impairment: No dosage adjustment necessary.
Severe kidney impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Note: Safety and effectiveness have not been established in patients with metabolic dysfunction–associated steatotic liver disease (formerly termed nonalcoholic steatohepatitis) cirrhosis.
Child-Turcotte-Pugh class A: No dosage adjustment necessary.
Child-Turcotte-Pugh class B and C: Avoid use.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Dermatologic: Pruritus (8% to 12%)
Gastrointestinal: Diarrhea (26% to 33%), nausea (17% to 22%)
Hepatic: Increased serum alanine aminotransferase (>3 × ULN: 11% to 13%), increased serum aspartate aminotransferase (>3 × ULN: 12%; >5 × ULN: 4%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (<5%), palpitations (<5%)
Dermatologic: Erythema of skin (<5%)
Endocrine & metabolic: Hypoglycemia (<5%)
Gastrointestinal: Abdominal pain (7% to 9%), abnormal stools (<5%), constipation (7% to 9%), decreased appetite (<5%), dysgeusia (<5%), flatulence (<5%), vomiting (9% to 10%)
Genitourinary: Abnormal uterine bleeding (<5%)
Hepatic: Increased serum bilirubin (>2 × ULN: 3%)
Nervous system: Depression (<5%), dizziness (6%), vertigo (<5%)
Neuromuscular & skeletal: Tendinopathy (<5%)
<1%: Hepatic: Hepatotoxicity
Frequency not defined:
Dermatologic: Skin rash, urticaria
Endocrine & metabolic: Decreased free T4
Gastrointestinal: Cholecystitis (acute), cholelithiasis, pancreatitis (obstructive)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Gallbladder: Gallbladder related adverse effects, including cholelithiasis, acute cholecystitis, and obstructive pancreatitis secondary to gallstones, have been observed.
• Hepatotoxicity: Substantial elevations in liver biochemistries requiring therapy interruption have been observed. In one patient, upon reintroduction of resmetirom, liver biochemistries again increased along with immunologic markers (eg, immunoglobulin G), suggesting drug induced liver injury, which resolved following subsequent discontinuation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Rezdiffra: 60 mg, 80 mg, 100 mg
No
Tablets (Rezdiffra Oral)
60 mg (per each): $164.64
80 mg (per each): $164.64
100 mg (per each): $164.64
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Oral: Administer with or without food.
Noncirrhotic metabolic dysfunction–associated steatotic liver disease : Treatment of noncirrhotic metabolic dysfunction–associated steatotic liver disease (formerly termed nonalcoholic steatohepatitis) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), in conjunction with diet and exercise, in adults.
Limitations of use: Avoid use in patients with decompensated cirrhosis.
Substrate of BCRP, CYP2C8 (Major with inhibitors), CYP2C8 (Minor with inducers), OATP1B1/1B3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP2C8 (Weak), OATP1B1/1B3;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider Therapy Modification
Asciminib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider Therapy Modification
Atorvastatin: Resmetirom may increase serum concentration of Atorvastatin. Management: Do not exceed atorvastatin doses of 40 mg daily during coadministration with resmetirom. Monitor for increased atorvastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider Therapy Modification
Atrasentan: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atrasentan. Risk X: Avoid
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider Therapy Modification
Bulevirtide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider Therapy Modification
Ceftobiprole Medocaril: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Cladribine: BCRP/ABCG2 Inhibitors may increase serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider Therapy Modification
CYP2C8 Inhibitors (Moderate): May increase serum concentration of Resmetirom. Management: During coadministration with moderate CYP2C8 inhibitors reduce the resmetirom dose to 80 mg daily for patients weighing 100 kg or more, or reduce the resmetirom dose to 60 mg daily for patients weighing less than 100 kg. Risk D: Consider Therapy Modification
CYP2C8 Inhibitors (Strong): May increase serum concentration of Resmetirom. Risk X: Avoid
Daprodustat: CYP2C8 Inhibitors (Weak) may increase serum concentration of Daprodustat. Risk C: Monitor
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix. Risk X: Avoid
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Eluxadoline: May increase serum concentration of Resmetirom. Resmetirom may increase serum concentration of Eluxadoline. Management: Avoid use of eluxadoline and resmetirom whenever possible. If combined, decrease the eluxadoline dose to 75 mg twice daily and monitor patients for increased effects and toxicities of both eluxadoline and resmetirom. Risk D: Consider Therapy Modification
Leniolisib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Lumacaftor and Ivacaftor: May decrease serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase serum concentration of CYP2C8 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Momelotinib. Risk C: Monitor
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase serum concentration of Resmetirom. Risk X: Avoid
PAZOPanib: BCRP/ABCG2 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pravastatin: Resmetirom may increase serum concentration of Pravastatin. Management: Limit the pravastatin dose to 40 mg daily during coadministration with resmetirom. Monitor for increased pravastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Repaglinide: CYP2C8 Inhibitors (Weak) may increase serum concentration of Repaglinide. Risk C: Monitor
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase active metabolite exposure of Revefenacin. Risk X: Avoid
Rosuvastatin: Resmetirom may increase serum concentration of Rosuvastatin. Management: Limit the rosuvastatin dose to 20 mg daily during coadministration with resmetirom. Monitor for increased rosuvastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider Therapy Modification
Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor
Simvastatin: Resmetirom may increase serum concentration of Simvastatin. Management: Limit the simvastatin dose to 20 mg daily during coadministration with resmetirom. Monitor for increased simvastatin adverse effects (eg, myalgias) during coadministration. Risk D: Consider Therapy Modification
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Taurursodiol. Risk X: Avoid
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Trofinetide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider Therapy Modification
Ubrogepant: BCRP/ABCG2 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider Therapy Modification
Voclosporin: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Voxilaprevir. Risk X: Avoid
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Zavegepant. Risk X: Avoid
Adverse events in rat reproduction studies occurred with decreases in maternal T4, T3, and TSH following oral doses ~21 times the maximum recommended human dose, based on AUC.
Data collection to monitor pregnancy and infant outcomes following exposure to resmetirom is ongoing. Report pregnancies to Madrigal Pharmaceuticals (1-800-905-0324 or https://www.madrigalpharma.com/contact/).
It is not known if resmetirom is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Evaluate liver biochemistries and signs or symptoms associated with liver (eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, eosinophilia) or gallbladder injury. Monitor for myopathy and rhabdomyolysis if concurrently used with HMG-CoA reductase inhibitors.
Resmetirom is a partial agonist of thyroid hormone receptor-beta (THR-β), the predominant thyroid hormone receptor in the liver. Stimulation of THR-β in the liver reduces intrahepatic triglycerides.
Distribution: Vdss: 68 L.
Protein binding: >99%.
Metabolism: Hepatic via CYP2C8.
Half-life elimination: 4.5 hours.
Time to peak: ~4 hours; steady state achieved after 3 to 6 days of repeated dosing.
Excretion: Feces: ~67%; urine: 24%; primarily excreted as metabolites.
Clearance:17.5 L/hour.
