REZDIFFRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REZDIFFRA (REZDIFFRA).
Rezdiffra (resmetirom) is a thyroid hormone receptor beta (THR-β) selective agonist. It reduces liver fat accumulation and fibrosis by increasing hepatic fat metabolism and reducing lipotoxicity through modulation of thyroid hormone signaling in the liver.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and other pathways. |
| Excretion | Fecal 90% (primarily as unchanged drug and minor metabolites), renal 10% (mostly metabolites, <3% unchanged). |
| Half-life | Terminal half-life 19 days (range 15–23 days), supporting monthly subcutaneous dosing for sustained malaria prophylaxis. |
| Protein binding | 99.7% bound to human serum albumin (HSA) and low-density lipoprotein (LDL). |
| Volume of Distribution | Approximately 17 L/kg (very large), indicating extensive tissue distribution and sequestration in hepatic parenchymal cells. |
| Bioavailability | Subcutaneous: ~76% (range 60–90%). |
| Onset of Action | Subcutaneous: clinical prophylaxis effect begins after the second weekly loading dose (day 8); full protective effect by day 10. |
| Duration of Action | Subcutaneous: clinical protection persists for approximately 1 month after the loading doses (2 weekly doses) and for 3 months after a single dose; extended protection due to slow elimination from liver. |
200 mg orally once daily for 14 days, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended for use in patients with eGFR <30 mL/min/1.73 m² due to lack of data. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No recommended dosing available. |
| Geriatric use | No specific dose adjustment required for geriatric patients; consider renal function and potential for increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REZDIFFRA (REZDIFFRA).
| Breastfeeding | Unknown excretion in human milk; M/P ratio not established. Consider risk-benefit; monitor infant for hypoglycemia if nursing. |
| Teratogenic Risk | No adequate human studies; animal studies show developmental toxicity at supra-therapeutic doses. Risk cannot be ruled out; first trimester exposure potential for malformations, third trimester risk of neonatal hypoglycemia if maternal hyperglycemia controlled. FDA Category: N (not assigned). |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["History of drug-induced liver injury or hypersensitivity to resmetirom.","Decompensated cirrhosis (Child-Pugh B/C).","Coadministration with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin).","Coadministration with strong CYP3A inducers (e.g., rifampin, carbamazepine)."]
| Precautions | ["Hepatotoxicity: Monitor liver enzymes; discontinue if ALT or AST elevations with bilirubin elevation occur.","Gallbladder disease: Cases of cholelithiasis and cholecystitis reported; monitor for symptoms.","Diarrhea: Common; manage with supportive care.","Drug interactions: Avoid strong CYP3A inhibitors and inducers; adjust dose with moderate CYP3A inhibitors."] |
Loading safety data…
| Monitor maternal blood glucose, HbA1c, renal function, liver enzymes; fetal surveillance with growth scans and nonstress tests in third trimester. |
| Fertility Effects | In animal studies, no adverse effects on fertility at clinically relevant doses; human data insufficient. |