Rezdiffra

C. Package leaflet: Information for the patient

Rezdiffra 60 mg film-coated tablets, 80 mg film-coated tablets, 100 mg film-coated tablets

resmetirom
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Rezdiffra is and what it is used for
2. What you need to know before taking Rezdiffra
3. How to take Rezdiffra
4. Possible side effects
5. How to store Rezdiffra
6. Contents of the pack and other information

1. What Rezdiffra is and what it is used for

Rezdiffra contains the active substance resmetirom.
Rezdiffra is a medicine used in adults for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). MASH is a liver disease in which fat accumulates in the liver, causing inflammation and damage to liver cells. Rezdiffra is used in adults who have evidence of inflammation and cellular damage, resulting in moderate scarring (stage 2 fibrosis) or significant scarring (stage 3 fibrosis).
The active substance in Rezdiffra, resmetirom, works by binding to and activating a protein called thyroid hormone receptor beta (THR-β), which is found in a type of liver cell known as hepatocytes. In patients with MASH, THR-β activity is reduced. By activating THR-β in the liver, resmetirom increases fat metabolism. This reduces the amount of fat present in the liver, which may help reduce inflammation and fibrosis, and improve liver function.

2. What you need to know before taking Rezdiffra

Do not take Rezdiffra

• if you are allergic to resmetirom or to any of the other ingredients of this medicine (listed in section 6);

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Rezdiffra.
In particular, inform your doctor if:

• you have liver problems other than MASH, such as a liver infection, including viral hepatitis (inflammation of the liver caused by a viral infection), or any liver disease involving the immune system (the body's natural defenses), including autoimmune hepatitis (liver inflammation caused by the immune system attacking the body's own cells) and primary biliary cholangitis (liver damage caused by the immune system attacking the bile ducts, the channels that carry bile from the liver);
• you consume alcoholic beverages or have liver damage due to alcohol use;
• you have gallbladder problems, including gallstones (small stones, usually made of cholesterol, that form in the gallbladder).

Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age. It is not known whether Rezdiffra is safe and effective in these individuals.

Other medicines and Rezdiffra
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor or pharmacist if you are taking any of the following medicines, as they may increase the level of Rezdiffra in your body and therefore increase the risk of side effects with Rezdiffra:

• clopidogrel (used to reduce blood clotting);
• deferasirox (used to remove excess iron from the body);
• gemfibrozil (used to reduce fats in the blood);
• teriflunomide (used to treat multiple sclerosis).

Inform your doctor or pharmacist if you are taking any of the following medicines, as Rezdiffra may increase the levels of these medicines in your body, which could increase the risk of side effects associated with them:

• atorvastatin, pravastatin, rosuvastatin, simvastatin (a group of medicines called statins used to lower cholesterol levels);
• pioglitazone (or other so-called CYP2C8 substrates, a specific class of medicines used to treat diabetes).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Rezdiffra has not been studied in pregnant women. The use of Rezdiffra is not recommended during pregnancy.
It is not known whether Rezdiffra passes into breast milk and could affect the breastfed infant. Your doctor will help you decide whether to stop breastfeeding or to avoid treatment with Rezdiffra, taking into account the benefits of breastfeeding for the infant and of Rezdiffra treatment for the mother.

Driving and using machines
This medicine does not alter or alters negligibly the ability to drive vehicles or operate machinery.

Rezdiffra contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., it is essentially "sodium-free".

3. How to take Rezdiffra

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
How much medicine to take
Rezdiffra is available as an oral tablet, to be taken with or without food. The dose of Rezdiffra depends on body weight. For patients who weigh:

• less than 100 kg, the recommended dose is 80 mg once daily;
• 100 kg or more, the recommended dose is 100 mg once daily.

Your doctor may adjust the dose depending on your liver function and if you are taking certain other medicines (see section “Other medicines and Rezdiffra”).
If you take more Rezdiffra than you should
Inform your doctor if you have taken or think you have taken too much Rezdiffra.
If you forget to take Rezdiffra
Do not take a double dose to make up for the missed dose. Take the next dose at your usual time.
If you stop taking Rezdiffra
Do not stop treatment with Rezdiffra without first consulting your doctor.
If you have any questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You may experience nausea and diarrhoea when you start taking Rezdiffra. These side effects are
usually mild and often resolve on their own within less than 3 weeks. If these problems do not resolve within 3 weeks or if they worsen, consult your doctor.

Very common (may affect more than 1 in 10 people):

• diarrhoea
• feeling unwell (nausea)

Common (may affect up to 1 in 10 people):

• itching

Uncommon (may affect up to 1 in 100 people):

• vomiting
• stomach ache (abdominal pain)
• constipation
• rash
• dizziness

Rare (may affect up to 1 in 1,000 people):

• inflammation of the pancreas due to a blockage (obstructive pancreatitis)
• gallstones (cholelithiasis)
• inflammation of the gallbladder (cholecystitis) or problems affecting the pancreas or bile duct
• itchy rash (urticaria)

Not known (frequency cannot be estimated from the available data):

• Abnormal liver function tests (hepatotoxicity)

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Rezdiffra

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.". The expiry date refers to the last day of the month.
Store below 30 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Rezdiffra contains

• The active substance is resmetirom.

Each film-coated tablet contains:

• Rezdiffra 60 mg: 60 mg of resmetirom.

• Rezdiffra 80 mg: 80 mg of resmetirom.

• Rezdiffra 100 mg: 100 mg of resmetirom.

• Other components are:

• Tablet core: microcrystalline cellulose, mannitol, croscarmellose sodium (see section 2 “Rezdiffra contains sodium”), anhydrous colloidal silica, magnesium stearate.

• Film coating of the tablet: poly(vinyl alcohol) alcohol, titanium dioxide (E171), macrogol, talc.

• Rezdiffra 80 mg film-coated tablets also contain yellow iron oxide (E172).

• Rezdiffra 100 mg film-coated tablets also contain yellow iron oxide (E172) and red iron oxide (E172).

Description of the appearance of Rezdiffra and contents of the pack

Rezdiffra 60 mg film-coated tablets are white, oval, 6.4 mm x 12.2 mm, with “P60” printed on one side and smooth on the other side.

Rezdiffra 80 mg film-coated tablets are yellow, oval, 7.1 mm x 13.5 mm, with “P80” printed on one side and smooth on the other side.

Rezdiffra 100 mg film-coated tablets are beige to pinkish in colour, oval, 7.6 mm x 14.6 mm, with “P100” printed on one side and smooth on the other side.

Rezdiffra film-coated tablets are packaged in PVC/PCTFE blisters with aluminium foil lidding.

Pack contents:

28 film-coated tablets

Marketing Authorisation Holder

Madrigal Pharmaceuticals EU Limited
1 Castlewood Avenue
Dublin
D06 H685
Ireland

Manufacturer

Corden Pharma GmbH
Otto-Hahn-Strasse 1
68723 Plankstadt
Germany

This medicinal product has been granted a marketing authorisation “subject to conditions”. This means that further data on this medicinal product are required. The European Medicines Agency will review new information on this medicinal product at least annually, and this package leaflet will be updated if necessary.

Further information

More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.