Safety profile of Rezdiffra

Adverse reactions leading to discontinuation

EAIR of Common Adverse Reactions Reported in 5% of patients in MAESTRO‑NASH*,†,‡

Adverse Reaction Placebo
n (EAIR§)
Rezdiffra 80 mg
n (EAIR§)
Rezdiffra 100 mg
n (EAIR§)
Diarrhea 52 (14) 78 (23) 98 (33)
Nausea 36 (9) 65 (18) 51 (15)
Pruritus 18 (4) 24 (6) 36 (10)
Vomiting 15 (4) 27 (7) 30 (8)
Constipation 18 (4) 20 (5) 28 (8)
Abdominal pain 18 (4) 22 (5) 27 (7)
Dizziness 6 (1) 17 (4) 17 (4)
*Population includes adult patients with noncirrhotic NASH with liver fibrosis (stages F2 and F3 at eligibility).
Median exposure duration was 68 weeks for placebo, 74 weeks for Rezdiffra 80 mg once daily, and 66 weeks for Rezdiffra 100 mg once daily.
EAIRs are per 100 PY where total PYs were 435, 435, and 407 for placebo, 80 mg once daily, and 100 mg once daily arms, respectively.
§The EAIR per 100 PY can be interpreted as an estimated number of first occurrences of the adverse reaction of interest if 100 patients are treated for 1 year.

Gastrointestinal adverse reactions

The EAIRs for gastrointestinal adverse reactions were: placebo: 57 per 100 PY; Rezdiffra 80 mg: 73 per 100 PY; and Rezdiffra 100 mg: 89 per 100 PY

Rezdiffra 80 mg
Rezdiffra 100 mg
Diarrhea Median time (Q1, Q3) to event, days 39 (2, 195) 17 (3, 70) 6 (2, 54)
Median duration, days 9 20 20
Nausea Median time (Q1, Q3) to event, days 85 (24, 347) 28 (2, 162) 5 (2, 40)
Median duration, days 17 26 28

Laboratory abnormalities

See how Rezdiffra works in the liver

ALT=alanine transaminase; AST=aspartate aminotransferase; EAIR=exposure-adjusted incidence rate; NASH=nonalcoholic steatohepatitis; PY=person-years; Q=quartile.






Hepatotoxicity has been observed in one patient. Please see full Prescribing Information for more details on this specific case of Hepatotoxicity [see Warnings and Precautions (5.1)].

Monitor patients during treatment for elevations in liver tests and for the development of liver-related adverse reactions. Monitor for symptoms and signs of hepatotoxicity (e.g., fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, and/or eosinophilia [>5%]). If hepatotoxicity is suspected, discontinue Rezdiffra and continue to monitor the patient. If laboratory values return to baseline, weigh the potential risks against the benefits of restarting Rezdiffra. If laboratory values do not return to baseline, consider DI-ALH or autoimmune liver disease in the evaluation of elevations in liver tests.

Gallbladder-Related Adverse Reactions

In clinical trials, cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone) were observed more often in Rezdiffra-treated patients than in placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an acute gallbladder event is suspected, interrupt Rezdiffra treatment until the event is resolved.

Drug Interaction with Certain Statins

Dosage adjustment for certain statins is recommended. Monitor for statin-related adverse reactions including but not limited to elevation of liver tests, myopathy, and rhabdomyolysis. Please see the upcoming Drug Interaction section of the Important Safety Information for more details.


The most common adverse reactions with Rezdiffra (reported in ≥ 5% of patients and higher compared to placebo) are: diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness. Diarrhea and nausea were the most common causes of treatment discontinuation.

Hypersensitivity Reactions

Reactions such as urticaria and rash, which may reflect drug hypersensitivity, were observed in patients receiving Rezdiffra.

Laboratory Abnormalities

Increases in mean ALT and AST levels were observed in the first 4 weeks after initiating treatment with Rezdiffra. The mean elevation in ALT and AST values was less than 1.5 times baseline at 4 weeks after treatment initiation. These values returned to baseline around 8 weeks after initiating treatment.


Clinically Significant Interactions Affecting Rezdiffra

Clinically Significant Interactions Affecting Other Drugs



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, such as increased risks of gestational diabetes, hypertensive complications, preterm birth, and postpartum hemorrhage. Report pregnancies to Madrigal Pharmaceuticals, Inc.’s Adverse Event reporting line at 1-800-905-0324 and


There is no information regarding the presence of Rezdiffra in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Rezdiffra and any potential adverse effects on the breastfed infant from Rezdiffra or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness have not been established in pediatric patients.

Geriatric Use

No overall differences in effectiveness but numerically higher incidence of adverse reactions have been observed in patients ≥65 years of age compared to younger adult patients.

Renal Impairment

The recommended dosage in patients with mild or moderate renal impairment is the same as in patients with normal kidney function. Rezdiffra has not been studied in patients with severe renal impairment.

Hepatic Impairment

Avoid use in patients with decompensated cirrhosis (consistent with moderate to severe hepatic impairment). Moderate or severe hepatic impairment (Child-Pugh Class B or C) increases resmetirom Cmax and AUC, which may increase the risk of adverse reactions.

No dosage adjustment is recommended for patients with mild hepatic impairment (Child-Pugh Class A).

The safety and effectiveness have not been established in patients with NASH cirrhosis.


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. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Limitation of Use: Avoid use in patients with decompensated cirrhosis.