Rezdiffra

2): • For patients weighing < 100 kg, the recommended dose is 80 mg taken orally once daily. • For patients weighing ≥ 100 kg, the recommended dose is 100 mg taken orally once daily. Missed or delayed doses If a dose of resmetirom is missed, the patient should take the next dose at the scheduled time.

A double dose should not be taken to make up for the missed dose. , gemfibrozil) is not recommended. 5). Special populations Hepatic impairment • Mild hepatic impairment No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh A).

2). • Moderate or severe hepatic impairment Increased exposure (Cmax and AUC) of resmetirom has been observed in patients with moderate or severe hepatic impairment. 2). Renal impairment • Mild renal impairment (eGFR 60 to 89 mL/min), moderate renal impairment (eGFR 30 to 59 mL/min) and severe renal impairment (eGFR 15 to 29 mL/min) No dose adjustment of resmetirom is recommended in patients with mild, moderate or severe renal impairment.

2). 2). 4 Paediatric population The safety and efficacy of resmetirom in children and adolescents less than 18 years old have not yet been established. No data are available. Method of administration Oral use. 2).

Summary of the safety profile The most frequently reported adverse reactions are diarrhoea, nausea, and pruritus. Diarrhoea typically occurred at treatment initiation, was mild to moderate and self-limiting, resolving on average in 2 to 3 weeks.

The median time to complete resolution of diarrhoea was 3 to 4 weeks. Nausea occurred at treatment initiation and was mild to moderate, occurring more commonly in female patients. Other rare events included cholecystitis and urticaria.

The most common reason for discontinuation in all age groups was withdrawal by subject. Tabulated list of adverse reactions Unless otherwise stated, the frequencies of adverse reactions in Table 1 are based on all-cause adverse event frequencies identified in patients randomised to the double-blind treatment arms of the Phase 3 clinical studies (MAESTRO-NASH and MAESTRO-NAFLD-1).

Adverse reactions are listed by MedDRA system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 1:

List of adverse reactions in MAESTRO-NASH and MAESTRO-NAFLD-1 System Organ Class Frequency: Adverse reactions Nervous system disorders Uncommon: Dizziness Gastrointestinal disorders Very Common: Diarrhoea, nausea Uncommon: Abdominal pain, constipation, vomiting Rare: Obstructive pancreatitis2 Hepatobiliary disorders Rare: Cholecystitis1,2, cholelithiasis Not known: Hepatotoxicity Skin and subcutaneous tissue disorders Common: Pruritus Uncommon: Rash Rare: Urticaria 1 The term “cholecystitis” includes Preferred Terms of bile duct stone, biliary colic, biliary dilatation, cholecystitis, cholecystitis acute, cholecystitis chronic and cholangitis.

2 A higher incidence of cholecystitis and obstructive pancreatitis (gallstone) was observed in the treatment arms compared to placebo. However, the Exposure Adjusted Incidence Rates (EAIRs) for these events were less than 1 per 100 patient years (PY) for all treatment arms.

Description of selected adverse reactions Liver enzyme elevations 7 Mild increases in mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in the first 4 weeks after initiating treatment with resmetirom.

These elevations were more common in patients on concomitant statin therapy. 5 times baseline at 4 weeks after treatment initiation. These values returned to baseline around 8 weeks after initiating treatment. Thyroid function tests A decrease in levels of prohormone free T4 (FT4) of mean 2%, 13%, and 17% was seen at 12 months in patients treated with placebo, resmetirom 80 mg once daily, and resmetirom 100 mg once daily, respectively, with minimal changes in active hormone T3 or in TSH.

There were no clinical findings associated with FT4 decreases. Other special populations Elderly Of the 1794 patients with MASH in clinical studies of resmetirom who received the recommended dose (80 mg or 100 mg), 440 (25%) were 65 years of age or older and 54 (3%) were 75 years of age or older.

Discontinuation rates among older patients ≥ 65 years of age in MAESTRO-NASH were higher at 100 mg than 80 mg. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Gallbladder events In clinical studies, cholecystitis was observed more often in resmetirom-treated patients than in placebo-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

Use in other liver diseases Resmetirom has not been studied in patients with other underlying liver diseases. Resmetirom should be used with caution in MASH patients with other underlying liver diseases such as autoimmune liver diseases or active viral hepatitis.

Resmetirom should be used with caution in patients with alcohol- related liver disease. Liver enzymes Conduct liver enzyme monitoring periodically during treatment. If hepatotoxicity is suspected, discontinue resmetirom treatment and continue to monitor liver chemistry.

Sodium content This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1.