II. Background
- Resmetirom is a specialty medication, first in class for NASH treatment, released in 2024
- Expensive at time of release ($4000/month) in 2024
III. Indications
-
Nonalcoholic Steatohepatitis (NASH, MASH)
- Refractory to lifestyle and comorbidity management and moderate to severe Hepatic Fibrosis
IV. Contraindications
- Decompensated Cirrhosis
- Moderate to severe hepatic imapirment (Child-Pugh Class B or C)
V. Mechanism
- Activates hepatic Thyroid Hormone Receptor Beta (THR-B Agonist)
- Increases hepatic Fat Metabolism and decreases hepatic fat deposition
VI. Medications
- Resmetirom 60 mg, 80 mg, 100 mg
VII. Dosing
- Weight <100 kg: Resmetirom 80 mg orally once daily
- Weight >100 kg: Resmetirom 100 mg orally once daily
VIII. Adverse Effects
- Gastrointestinal (common)
- Acute Gallbladder dysfunction (uncommon)
- Includes Cholelithiasis, Cholecystitis, Gallstone Pancreatitis
- Hepatotoxicity
- Monitor Liver Function Tests
- Monitor for hepatotoxicity signs (Nausea, Vomiting, RUQ Abdominal Pain, Jaundice)
IX. Safety
- Unknown safety in pregnancy
- Unknown safety in Lactation
X. Drug Interactions
-
Statins
- Resmetirom increases Statin plasma concentrations
- Limit Simvastatin to 20 mg/day
- Limit Rosuvastatin to 20 mg/day
- Limit Pravastatin to 40 mg/day
- Limit Atorvastatin to 40 mg/day
- Moderate to Strong CYP2C8 Inhibitors
- Avoid strong CYP2C8 Inhibitors (e.g. Gemfibrozil) in combination with Resmetirom
- Moderate CYP2C8 Inhibitor (e.g. cloipidogrel)
- Weight <100 kg: Limit Resmetirom dose to 60 mg
- Weight >100 kg: Limit Resmetirom dose to 80 mg
- OATP1B1 and OATP1B3 Inhibitors (e.g. Cyclosporine)
- Avoid in combination with Resmetirom
XI. Efficacy
XII. Resources
XIII. References
- (2024) Presc Lett 31(7): 39
- Harrison (2024) N Engl J Med 390(6):497-509 +PMID: 38324483 [PubMed]