Resmetirom
Generic Name: resmetirom
Brand Names:
Rezdiffra
11 DESCRIPTION REZDIFFRA (resmetirom) tablets contain resmetirom, a thyroid hormone receptor-beta agonist. The chemical name for REZDIFFRA is 2-[3,5-Dichloro-4-((6-oxo-5-(propan-2-yl)-1,6-dihydropyridazin-3-yl)oxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile. The molecular formula is C 17 H 12 Cl 2 N 6 O 4 and the molecular weight is 435.22. The chemical structure is: Resmetirom has low aqueous solubility below pH 6 and higher solubility above pH 7 (0.44 mg/mL at pH 7.04).
Overview
11 DESCRIPTION REZDIFFRA (resmetirom) tablets contain resmetirom, a thyroid hormone receptor-beta agonist. The chemical name for REZDIFFRA is 2-[3,5-Dichloro-4-((6-oxo-5-(propan-2-yl)-1,6-dihydropyridazin-3-yl)oxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitrile. The molecular formula is C 17 H 12 Cl 2 N 6 O 4 and the molecular weight is 435.22. The chemical structure is: Resmetirom has low aqueous solubility below pH 6 and higher solubility above pH 7 (0.44 mg/mL at pH 7.04).
Uses
1 INDICATIONS AND USAGE 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) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitations of Use Avoid use of REZDIFFRA in patients with decompensated cirrhosis [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] .
Dosage
2 DOSAGE AND ADMINISTRATION 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.
Side Effects
6 ADVERSE REACTIONS 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 .
Interactions
7 DRUG INTERACTIONS Strong or Moderate CYP2C8 Inhibitors: Concomitant use not recommended (strong inhibitor [e.g., gemfibrozil]); or reduce REZDIFFRA dosage (moderate inhibitor [e.g., clopidogrel]). (2.2 , 7.1) Atorvastatin, Pravastatin, Rosuvastatin and Simvastatin : Limit the daily dosage of the statin as recommended. (5.3 , 7.2) CYP2C8 Substrates: Monitor patients more frequently for substrate- related adverse reactions. (7.2) 7.1 Effects of Strong or Moderate CYP2C8 Inhibitors on REZDIFFRA Table 3 includes clinically significant drug interaction effects of strong or moderate CYP2C8 inhibitors on REZDIFFRA. Table 3: Clinically Significant Interaction Effects of Strong or Moderate CYP2C8 Inhibitors on REZDIFFRA Clinical Impact Resmetirom is a CYP2C8 substrate.
Warnings
5 WARNINGS AND PRECAUTIONS 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. 4 CONTRAINDICATIONS None. None.
Storage
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied REZDIFFRA (resmetirom) tablets are packaged in white high-density polyethylene bottles closed with a child-resistant closure containing an induction seal. 60 mg Tablets : white oval-shaped film-coated tablets, debossed “P60” on one side and plain on the other side.
Frequently Asked Questions
What is Resmetirom used for?▼
1 INDICATIONS AND USAGE 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) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitations of Use Avoid use of REZDIFFRA in patients with decompensated cirrhosis [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] .
What are the side effects of Resmetirom?▼
6 ADVERSE REACTIONS 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 .
What are the important warnings for Resmetirom?▼
5 WARNINGS AND PRECAUTIONS 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. 4 CONTRAINDICATIONS None. None.
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Medical Disclaimer
This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.