Rezdiffra Drug Interactions: What You Need to Know

If you're taking Rezdiffra (Resmetirom) for NASH/MASH, it's important to understand how it interacts with other medications. Some drug interactions can change how well Rezdiffra works, increase the risk of side effects, or require dose adjustments.

This guide covers the major and moderate drug interactions for Rezdiffra, plus supplements, over-the-counter products, and food considerations. Bring this information to your next doctor's appointment — or better yet, bring a complete list of everything you take.

How Drug Interactions Work

Drug interactions happen when one medication affects how another is absorbed, processed, or eliminated by your body. With Rezdiffra, interactions mainly involve:

• CYP2C8 enzyme pathway: Rezdiffra is metabolized (broken down) by an enzyme called CYP2C8 in the liver. Drugs that block this enzyme can cause Rezdiffra to build up in your body to higher-than-intended levels.
• OATP1B1/OATP1B3 transporters: These are proteins that help move drugs into liver cells. Some medications block these transporters, which can affect how Rezdiffra enters the liver.
• Statin metabolism: Rezdiffra increases the blood levels of several statins, which can raise the risk of statin-related muscle problems.

Major Drug Interactions

These interactions are significant and may require avoiding the combination entirely or making important dose changes:

Gemfibrozil (Lopid)

Gemfibrozil is a fibrate used to lower triglycerides and cholesterol. It is a strong CYP2C8 inhibitor, meaning it can significantly increase Rezdiffra levels in your body. Using Gemfibrozil with Rezdiffra is not recommended. If you need triglyceride-lowering therapy, your doctor may suggest an alternative like Fenofibrate, which does not have the same interaction.

Cyclosporine (Neoral, Sandimmune, Gengraf)

Cyclosporine is an immunosuppressant used after organ transplant and for certain autoimmune conditions. It inhibits OATP1B1 and OATP1B3 transporters, which can increase Rezdiffra exposure. If you must take both, your doctor should reduce your Rezdiffra dose to 60 mg daily.

Statins (Dose Limits Apply)

Rezdiffra increases blood levels of several commonly prescribed statins. This raises the risk of myopathy (muscle pain and weakness) and, in rare cases, rhabdomyolysis (a serious condition where muscle tissue breaks down). When taking Rezdiffra, the following statin dose limits apply:

• Atorvastatin (Lipitor): Limit to 40 mg/day
• Pravastatin (Pravachol): Limit to 40 mg/day
• Rosuvastatin (Crestor): Limit to 20 mg/day
• Simvastatin (Zocor): Limit to 20 mg/day

If you're currently taking a statin at a higher dose, your doctor will need to adjust it before starting Rezdiffra. Do not change your statin dose on your own — always work with your doctor.

Report any muscle pain, tenderness, weakness, or dark-colored urine to your doctor immediately, as these could be signs of statin-related muscle damage.

Moderate Drug Interactions

Clopidogrel (Plavix)

Clopidogrel is a blood thinner used to prevent heart attacks and strokes. It is a moderate CYP2C8 inhibitor. If you take Clopidogrel with Rezdiffra, your doctor may need to reduce your Rezdiffra dose and monitor you more closely for side effects.

CYP2C8 Substrates

Medications that are processed by the CYP2C8 enzyme may be affected when taken alongside Rezdiffra. Your doctor should monitor you more frequently for adverse reactions if you're taking other CYP2C8 substrates. Examples include certain diabetes medications like Repaglinide and Rosiglitazone.

Supplements and Over-the-Counter Products to Watch

While Rezdiffra doesn't have a long list of supplement interactions, it's still important to tell your doctor about everything you take, including:

• Vitamin E (high-dose): Some NASH patients take high-dose Vitamin E. While there's no known direct interaction with Rezdiffra, combining multiple liver-targeted treatments should be discussed with your doctor.
• Herbal liver supplements: Products containing milk thistle, turmeric, or other "liver detox" ingredients may affect liver enzymes. Since Rezdiffra is processed through the liver, tell your doctor about any herbal supplements you're using.
• Over-the-counter pain relievers: Acetaminophen (Tylenol) is processed by the liver and should be used cautiously in patients with liver disease. While it doesn't directly interact with Rezdiffra, excessive use can add stress to an already compromised liver. NSAIDs like Ibuprofen (Advil) and Naproxen (Aleve) should also be discussed with your doctor.

Food and Drink Interactions

The good news: Rezdiffra has no significant food interactions. You can take it with or without food, and there are no specific foods you need to avoid.

That said, general dietary advice for NASH/MASH patients still applies:

• Limit alcohol: While Rezdiffra itself doesn't have a specific alcohol interaction listed, alcohol is harmful to the liver and can worsen NASH/MASH. Most doctors recommend minimizing or eliminating alcohol intake.
• Follow a liver-friendly diet: A Mediterranean-style diet rich in fruits, vegetables, whole grains, lean protein, and healthy fats supports liver health and complements your Rezdiffra treatment.

What to Tell Your Doctor

Before starting Rezdiffra, make sure your doctor has a complete picture of what you're taking. Here's a checklist:

• All prescription medications — especially statins, Gemfibrozil, Cyclosporine, Clopidogrel, and diabetes medications
• Over-the-counter drugs — including pain relievers, antacids, and allergy medications
• Supplements and vitamins — including Vitamin E, fish oil, and any herbal products
• Recent medication changes — if you've started or stopped anything in the last few months

If you're seeing multiple specialists (which is common for patients with NASH/MASH, diabetes, and heart disease), make sure each doctor knows about your Rezdiffra prescription. A pharmacist can also help review your full medication list for potential interactions.

Final Thoughts

Rezdiffra's drug interactions are manageable, but they require attention — especially if you're taking statins or other liver-metabolized medications. The most important thing you can do is be upfront with your healthcare team about everything you take.

For more on what to expect when taking Rezdiffra, see our guides on side effects and dosage information. When you're ready to fill your prescription, use Medfinder to check pharmacy availability near you.