What You Need to Know About Rezdiffra Side Effects

Starting a new medication can feel overwhelming, especially when it's a specialty drug like Rezdiffra (Resmetirom). Understanding what side effects to expect — and which ones need immediate medical attention — can help you feel more confident about your treatment.

This guide covers the common and serious side effects of Rezdiffra, based on FDA-approved labeling, so you know exactly what to watch for.

What Is Rezdiffra?

Rezdiffra is a prescription medication approved by the FDA in March 2024 for the treatment of noncirrhotic NASH/MASH (nonalcoholic steatohepatitis / metabolic dysfunction-associated steatohepatitis) with moderate to advanced liver fibrosis (stages F2–F3). It works by activating thyroid hormone receptor-beta (THR-β) in the liver to reduce fat, inflammation, and fibrosis. For a deeper dive into how it works, see our post on Rezdiffra's mechanism of action.

It's taken as a once-daily tablet, with the dose based on your body weight: 80 mg if you weigh less than 220 lbs (100 kg), or 100 mg if you weigh 220 lbs or more. For full details on dosing, see What Is Rezdiffra?

Common Side Effects of Rezdiffra

In clinical trials, the most frequently reported side effects included:

• Diarrhea — One of the most common side effects. It's usually mild to moderate and may improve over the first few weeks of treatment.
• Nausea — Some patients feel queasy, especially when first starting the medication. Taking Rezdiffra with food may help.
• Vomiting — Less common than nausea but can occur, particularly early in treatment.
• Constipation — Some patients experience the opposite of diarrhea. Staying hydrated and eating fiber-rich foods can help.
• Abdominal pain — Stomach discomfort or cramping may occur. This is usually mild.
• Pruritus (itching) — Some patients report itchy skin, which may or may not be related to liver function changes.
• Dizziness — Occasional dizziness has been reported. Avoid driving or operating heavy machinery if you feel lightheaded.

Most of these side effects are mild to moderate and tend to improve as your body adjusts to the medication. If any of them become severe or persistent, talk to your doctor.

Serious Side Effects of Rezdiffra

While less common, Rezdiffra carries some important risks that require medical attention:

Hepatotoxicity (Liver Injury)

Rezdiffra can cause elevated liver enzymes, which may indicate liver damage. Your doctor will monitor your liver function through blood tests before and during treatment. Call your doctor right away if you experience:

• Yellowing of the skin or eyes (jaundice)
• Dark-colored urine
• Unusual fatigue or weakness
• Pain in the upper right side of your abdomen

Gallbladder Problems

Rezdiffra has been associated with cholelithiasis (gallstones) and acute cholecystitis (gallbladder inflammation). In rare cases, gallstones can lead to obstructive pancreatitis. Symptoms to watch for include:

• Sudden, intense pain in the upper right abdomen or center of the abdomen
• Pain that radiates to the back or right shoulder
• Nausea and vomiting that accompanies abdominal pain
• Fever or chills

If you experience these symptoms, seek medical attention promptly.

Drug-Induced Autoimmune-Like Hepatitis (DI-ALH)

In rare cases, Rezdiffra may trigger an autoimmune-like response in the liver. Your doctor will monitor for this with regular lab work.

Hypersensitivity Reactions

Allergic reactions including urticaria (hives) and rash have been reported. If you develop widespread hives, swelling of the face or throat, or difficulty breathing, seek emergency medical care immediately.

Side Effects in Specific Populations

Pregnancy and Breastfeeding

The safety of Rezdiffra during pregnancy and breastfeeding has not been established. If you're pregnant, planning to become pregnant, or nursing, talk to your doctor before starting or continuing Rezdiffra.

Pediatric Patients

Rezdiffra has not been studied in children. It is not approved for use in patients under 18.

Patients with Severe Liver Disease

Rezdiffra is not recommended for patients with decompensated cirrhosis or severe hepatic impairment. If your liver disease has progressed beyond F3 fibrosis, your doctor will likely recommend other treatment approaches.

How to Manage Side Effects

Here are some practical tips for dealing with the most common side effects:

• For diarrhea: Stay hydrated, eat bland foods (bananas, rice, toast), and avoid greasy or spicy meals. Over-the-counter remedies like Loperamide (Imodium) may help — ask your doctor first.
• For nausea: Take Rezdiffra with a light meal or snack. Avoid lying down immediately after taking it. Ginger tea or crackers may ease symptoms.
• For itching: Use fragrance-free moisturizers, avoid hot showers, and wear loose-fitting clothing. If itching is severe, your doctor may recommend an antihistamine.
• For dizziness: Stand up slowly from sitting or lying positions. Make sure you're staying hydrated and eating regularly.
• For constipation: Increase fiber intake, drink plenty of water, and consider a mild stool softener if needed.

Keep a symptom journal during your first few months on Rezdiffra. This makes it easier to discuss side effects with your doctor at follow-up appointments.

When to Call Your Doctor

Contact your healthcare provider if you experience:

• Any serious side effects listed above (jaundice, severe abdominal pain, allergic reactions)
• Side effects that don't improve after the first few weeks
• New or worsening symptoms at any point during treatment
• Muscle pain, tenderness, or weakness — especially if you're also taking a statin (Rezdiffra can increase statin levels in your blood, raising the risk of drug interactions)

Final Thoughts

Most people who take Rezdiffra tolerate it well. The common side effects — diarrhea, nausea, and itching — are usually manageable and tend to ease over time. The serious risks, while uncommon, are important to know about so you can act quickly if something doesn't feel right.

Talk to your doctor about what to watch for, keep up with your scheduled lab work, and don't hesitate to reach out if something feels off. If you're still looking for a prescriber, check out our guide on how to find a doctor who can prescribe Rezdiffra. And if you're ready to fill your prescription, use Medfinder to check availability near you.