Rezdiffra (Resmetirom) Side Effects: What to Expect and When to Call Your Doctor

Like all medications, Rezdiffra (resmetirom) can cause side effects. The good news is that in clinical trials involving more than 2,000 patients, the overall safety profile was favorable — most side effects were gastrointestinal and tended to be mild to moderate in severity. However, there are serious warnings you should know.

This guide covers everything you need to know about Rezdiffra's side effects — what is common, what is serious, and exactly when you should call your doctor.

Common Side Effects of Rezdiffra (Resmetirom)

In the MAESTRO-NASH Phase 3 trial, the most common side effects reported in 5% or more of patients taking Rezdiffra (and more often than placebo) were:

Diarrhea — the most commonly reported side effect. Usually begins early in treatment and is mild to moderate in severity. Was one of the most common reasons for stopping treatment in clinical trials.

Nausea — also typically starts early and often improves over time. Along with diarrhea, it was one of the top reasons patients stopped treatment.

Pruritus (itching) — generalized itching was reported in some patients. If severe, discuss with your doctor.

Vomiting — occurred more commonly with Rezdiffra than with placebo.

Constipation — some patients experienced constipation, contrasting with the more common diarrhea.

Abdominal pain — stomach discomfort or cramping. If severe or accompanied by jaundice, seek immediate medical attention.

Dizziness — was reported more often in patients on Rezdiffra than placebo. Use caution when operating machinery until you know how the drug affects you.

Most of these GI side effects appeared early in treatment and were manageable. If you experience persistent diarrhea or nausea, speak with your doctor — do not stop the medication on your own without guidance.

Serious Side Effects: What Requires Urgent Medical Attention

While uncommon, Rezdiffra carries two serious safety warnings that require prompt attention:

1. Liver Injury (Hepatotoxicity)

Cases of liver injury (hepatotoxicity) have been reported in patients taking Rezdiffra. Paradoxically, this can occur even though Rezdiffra is designed to protect liver tissue. In clinical trials, one case of significant hepatotoxicity was observed in the safety study. Rezdiffra should be discontinued if liver injury is suspected.

Call your doctor immediately if you experience:

Unusual tiredness or fatigue

Yellowing of the skin or whites of the eyes (jaundice)

Pain or tenderness in the upper right or middle abdomen

Fever or rash in combination with other liver symptoms

Nausea or vomiting that is new or worsening

2. Gallbladder Problems (Cholelithiasis and Cholecystitis)

Gallstones (cholelithiasis), gallbladder inflammation (cholecystitis), and obstructive pancreatitis from gallstones were reported more frequently in Rezdiffra-treated patients than in placebo patients, though the absolute rates were low (less than 1 event per 100 person-years). The prescribing information recommends interrupting Rezdiffra if an acute gallbladder event is suspected until the condition resolves.

Seek prompt care if you experience:

Sudden, severe pain in the right upper abdomen or between the shoulder blades

Nausea or vomiting accompanying abdominal pain

Fever along with abdominal pain (possible cholecystitis)

Drug Interaction Risks You Should Know About

Rezdiffra interacts with several common medications, which can increase the risk of side effects from both drugs:

Statins: Rezdiffra increases blood levels of certain statins. Rosuvastatin and simvastatin doses must be limited to 20 mg/day; pravastatin and atorvastatin to 40 mg/day. Watch for muscle pain, weakness, or darkened urine.

Gemfibrozil: Avoid using with Rezdiffra — this strong CYP2C8 inhibitor significantly increases resmetirom blood levels.

Cyclosporine and certain antibiotics (erythromycin): These OATP inhibitors increase Rezdiffra levels and should be avoided or used with caution.

Rezdiffra and Pregnancy

There are no adequate studies of Rezdiffra use in pregnant women. There are theoretical risks because MASH itself is associated with gestational complications. If you are pregnant, planning to become pregnant, or breastfeeding, discuss this with your doctor before starting Rezdiffra. A pregnancy safety study is ongoing; report pregnancies to Madrigal Pharmaceuticals at 1-800-905-0324.

Managing Common Side Effects

Diarrhea: Stay hydrated. Ask your doctor about over-the-counter antidiarrheals like loperamide if symptoms are persistent.

Nausea: Take with food if nausea is a concern. Small, frequent meals may help. Tell your doctor if nausea is severe.

Dizziness: Rise slowly from a seated or lying position. Avoid driving or operating heavy machinery until you know how Rezdiffra affects you.

For more detailed information on drug interactions, see: Rezdiffra Drug Interactions: What to Avoid and What to Tell Your Doctor.