Rezdiffra

Pronunciation: rez-di-frah
Generic name: resmetirom
Dosage form: oral tablets (60mg, 80mg, 100mg)
Drug class: Miscellaneous metabolic agents

Medically reviewed by Carmen Pope, BPharm. Last updated on Mar 15, 2024.

What is Rezdiffra?

Rezdiffra (resmetirom) is an oral (taken by mouth) THR-beta agonist that may be used to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It should be used alongside diet and exercise.

NASH is also known as nonalcoholic fatty liver disease or metabolic dysfunction-associated steatohepatitis [MASH].

Rezdiffra is a partial agonist of thyroid hormone receptor-beta (THR-beta) which is the major thyroid hormone receptor in the liver and works by stimulating this receptor which reduces triglyceride levels within the liver. High levels of lipids within the liver are associated with NASH and symptoms such as liver swelling, fibrosis, and cirrhosis.

NASH resolution with no worsening of fibrosis was reported in 25.9% (80mg dose) and 29.9% (100mg dose) versus 9.7% (placebo [inactive medication]) after 52 weeks in a Phase 3 clinical trial of 966 adults with biopsy-confirmed NASH and a fibrosis stage range of F1B to F3. In addition:

24.2% (80mg) and 25.9% (100mg) of patients experienced an improvement in their fibrosis by at least one stage with no worsening in their NAFLD activity score
LDL levels also decreased by 13.6% (80mg) and 16.3% (100mg), compared with 0.1% in the placebo group.

Rezdiffra was FDA approved on 14 March, 2024 and was the first drug to be approved for NASH. Its approval is under the accelerated approval scheme, which means its continued approval may be based on the results of further clinical trials.

Warnings

May cause liver toxicity. Your healthcare provider will monitor you for increases in your liver enzyme levels and the development of liver-related side effects. Should not be used in people with moderate-to-severe liver disease (Child-Pugh Class B or C).

Gallbladder-related side effects, such as cholelithiasis and cholecystitis have been associated with Rezdiffra. Your healthcare provider will monitor you for these and may conduct further diagnostic tests if appropriate.

It is not known if Rezdiffra is safe and effective in children under the age of 18.

Before taking

Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you:

have any liver problems other than NASH
have gallbladder problems or have been told you have gallbladder problems, including gallstones
are taking other medications such as gemfibrozil to lower your cholesterol or cyclosporine to suppress your immune system, because some of these may not be recommended
are pregnant or plan to become pregnant
are breastfeeding or plan to breastfeed.

Pregnancy

It is not known if Rezdiffra will harm your unborn baby. Talk to your healthcare provider about the risk to the baby from Rezdiffra if you become pregnant. Report pregnancies to Madrigal Pharmaceuticals, Adverse Event reporting line at 1-800-905-0324 and https://www.madrigalpharma.com/contact/

Breastfeeding

It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while you are taking it.

How is Rezdiffra administered?

Take Rezdiffra exactly as your healthcare provider tells you to take it.

Your dose is based on your body weight. Your healthcare provider will calculate this for you and it may depend on what other medications you take. The recommended dosage of Rezdiffra is:

Body weight less than 100kg: 80mg once daily
Body weight of 100kg or more: 100mg once daily.

Take your dose of Rezdiffra one time a day, by mouth.

Choose the time of day when you are most likely to remember to take your dose.
You can take it with or without food.

What are the side effects of Rezdiffra?

Rezdiffra may cause serious side effects, including:

Liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop:

tiredness
fever
pain or tenderness in the upper middle or upper right area of your stomach (abdomen)
nausea
rash
vomiting
your skin or the white part of your eyes turns yellow (jaundice)

Gallbladder problems. Problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur because of NASH or Rezdiffra. Call your healthcare provider right away if you develop nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting.

The most common side effects of Rezdiffra affecting at least 5% of patients include:

Diarrhea
Itching
Vomiting
Constipation
Nausea
Stomach (abdominal) pain
Dizziness.

These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to www.fda.gov/medwatch.

What other drugs will affect Rezdiffra?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take medicines such as:

Strong CYP2C8 inhibitors, such as gemfibrozil (concomitant use not recommended)
Moderate CYP2C8 inhibitors, such as clopidogrel (reduce dosage)
OATP1B1 and OATP1B3 inhibitors, such as cyclosporine (concomitant use not recommended)
Statins, such as atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin (limit the statin dosage)
CYP2C8 substrates, such as loperamide, montelukast, or paclitaxel (may increase the risk of side effects).

This is not a complete list of interactions. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Storage

Store at room temperature between 68ºF to 77ºF (20ºC to 25ºC).

Ingredients

Active ingredient: resmetirom.

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, and microcrystalline cellulose.

Film coating: polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide, red iron oxide (100 mg tablets), and yellow iron oxide (80 mg and 100 mg tablets).