Resmirom60 mg

Resmirom is indicated, in combination with diet and exercise, for the treatment of adults with non-cirrhotic nonalcoholic steatohepatitis (NASH), also termed metabolic dysfunction-associated steatohepatitis (MASH), who have moderate to advanced liver fibrosis (consistent with fibrosis stages F2 to F3).

• Established/approved use: Non-cirrhotic MASH/NASH with moderate-to-advanced fibrosis (F2-F3), always used together with diet and exercise, not as monotherapy replacing lifestyle measures.
• Regulatory status: Resmirom was approved under an accelerated approval pathway based on improvement in liver histology (fibrosis and steatohepatitis); continued approval may depend on verification of clinical benefit in ongoing confirmatory trials.
• Not indicated for patients with compensated or decompensated cirrhosis (F4 fibrosis) - safety and efficacy have not been established in this population.

The diagnosis of MASH/NASH and the stage of fibrosis should be confirmed by a physician, typically using liver biopsy or validated non-invasive tests, before starting Resmirom.

Each film-coated tablet of Resmetirom contains Resmetirom as the active ingredient, commonly available in strengths of 60 mg, 80 mg, and 100 mg. Tablets also contain standard pharmaceutical excipients such as fillers, binders, and coating agents. Exact excipient composition may vary by manufacturer; refer to the specific product's package insert for full details.

Resmirom is an orally administered, liver-directed, thyroid hormone receptor-beta (THR-beta) selective agonist. It is the first medicine approved specifically for non-cirrhotic MASH/NASH with fibrosis. By selectively activating THR-beta in the liver, Resmirom is designed to improve hepatic fat metabolism and reduce liver fat, inflammation, and fibrosis associated with steatohepatitis, while minimizing effects on thyroid hormone receptor-alpha (found in heart and bone) that are responsible for many unwanted systemic thyroid hormone effects.

Resmirom is supplied as oral film-coated tablets and is used together with dietary and lifestyle modification as part of a comprehensive treatment plan for liver fibrosis due to MASH/NASH.

Resmirom belongs to the therapeutic class of thyroid hormone receptor-beta (THR-beta) selective agonists, a novel class of agents used for the management of metabolic liver disease. It is classified specifically as an agent for non-cirrhotic MASH/NASH with liver fibrosis, distinct from other hepatology drug classes such as antivirals or hepatoprotectants.

Mechanism of action: Resmetirom selectively activates the thyroid hormone receptor-beta isoform, which is the predominant thyroid hormone receptor in the liver. Activation of hepatic THR-beta increases mitochondrial fatty acid beta-oxidation, reduces hepatic lipogenesis, lowers intrahepatic triglyceride content, and improves clearance of low-density lipoprotein (LDL) cholesterol. These effects collectively reduce liver fat and are believed to reduce the inflammatory and fibrotic processes that drive progression of MASH/NASH.

Pharmacokinetics: Resmetirom is absorbed orally, undergoes hepatic metabolism (partly via CYP2C8 and other pathways), and is eliminated primarily through the biliary/fecal route. Because CYP2C8 is involved in its metabolism, co-administration with CYP2C8 inhibitors or inducers can significantly change Resmetirom exposure (see Drug Interactions). Resmetirom and/or its metabolites can also inhibit certain hepatic transporters (e.g., BCRP, OATP1B1/1B3), which affects the levels of co-administered drugs that use these transporters, notably certain statins.

Resmirom tablets are taken by mouth, once daily, with or without food, and should be swallowed whole. Do not stop or change the dose of Resmirom without consulting a physician, as underlying liver disease requires ongoing monitoring.

Statins: Resmirom increases systemic exposure to certain statins by inhibiting hepatic uptake transporters (OATP1B1/1B3) and BCRP. When co-administered with Resmirom, doses of atorvastatin and pravastatin should generally not exceed 40 mg daily, and doses of rosuvastatin and simvastatin should generally not exceed 20 mg daily; monitor for statin-related adverse effects (e.g., myopathy).

CYP2C8 inhibitors/inducers: Strong CYP2C8 inhibitors (e.g., gemfibrozil) can substantially increase Resmirom exposure and should generally be avoided; moderate CYP2C8 inhibitors require a reduced dose of Resmirom. Strong CYP2C8 inducers may reduce Resmirom effectiveness.

Other CYP2C8/BCRP/OATP1B1/1B3 substrate drugs: Resmirom may increase the exposure of other drugs that are substrates of these enzymes/transporters, requiring dose adjustment or closer monitoring per physician judgment.

Warfarin and other anticoagulants: Concomitant use with Resmirom may warrant closer monitoring of anticoagulant effect (e.g., INR) due to potential pharmacokinetic interplay; adjust dose as clinically indicated.

Thyroid hormone-related medicines: Because Resmirom acts on thyroid hormone receptors, caution and monitoring are advised when used together with thyroid hormone replacement or other thyroid-active agents.

Always inform your physician or pharmacist of all medicines, supplements, and herbal products being used before starting Resmirom.

The most commonly reported side effects of Resmirom include:

• Diarrhea (usually mild to moderate, often occurring early in treatment)
• Nausea and vomiting
• Pruritus (itching)
• Constipation
• Abdominal pain
• Dizziness

Liver enzyme elevations: Changes in liver function tests can occur; periodic monitoring is recommended (see Precautions and Warnings).

Gallbladder-related events: Cholelithiasis (gallstones) and cholecystitis have been reported more frequently with Resmirom than with placebo in clinical trials; report symptoms such as severe upper abdominal pain, fever, or jaundice promptly.

Contact a physician if side effects are severe, persistent, or concerning.

Pregnancy: Data on the use of Resmirom in pregnant women are limited. Animal studies have shown adverse developmental effects at doses associated with maternal toxicity. Because MASH/NASH with liver fibrosis itself carries risks to mother and fetus, and safety data for Resmirom in pregnancy are limited, use during pregnancy should generally be avoided unless a physician determines the potential benefit clearly justifies the potential risk. Discuss pregnancy plans and effective contraception with a physician before starting Resmirom.

Lactation: It is not known whether Resmirom or its metabolites are present in human milk, or their effects on a breastfed infant or on milk production. Use during breastfeeding should be discussed with a physician, weighing the mother's clinical need against potential infant risk.

Hepatotoxicity/liver monitoring: Because Resmirom is used in patients with underlying liver disease and can itself cause liver enzyme elevations, liver function tests should be monitored periodically during treatment, as advised by a physician. Rare cases resembling drug-induced autoimmune-like hepatitis have been reported; discontinue Resmirom and seek medical evaluation promptly if signs of liver injury occur (e.g., jaundice, dark urine, severe fatigue, right upper abdominal pain).

Not for use in cirrhosis: Resmirom is not indicated and has not been adequately studied in patients with cirrhosis, including decompensated cirrhosis; it should not be used in this setting (see Contraindications/Indications).

Gallbladder disease: Monitor for signs and symptoms of cholelithiasis or cholecystitis; interrupt Resmirom if an acute gallbladder event is suspected pending evaluation.

Newly approved medicine: Resmirom was approved relatively recently and long-term real-world safety data are still accumulating; ongoing confirmatory studies continue to evaluate its benefits and risks. Use strictly under physician supervision with recommended monitoring.

Drug interactions: Review all concomitant medicines, especially statins and CYP2C8-interacting drugs, before and during therapy (see Drug Interactions).

Limited clinical data exist regarding acute overdose with Resmirom. In case of a suspected overdose, seek immediate medical attention or contact emergency services/a poison control center. Treatment of overdose should be supportive and symptomatic, guided by a physician, with monitoring of liver function and vital signs as appropriate; there is no specific antidote for Resmirom overdose.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Hepatic Impairment

Resmirom is used specifically in patients with liver fibrosis due to MASH/NASH; however, it is not indicated for patients with cirrhosis (compensated or decompensated), and dosing in significant hepatic impairment beyond the studied population has not been established. Use only under close physician supervision with liver monitoring.

Renal Impairment

No specific dose adjustment has been established for renal impairment based on available data; use with caution and physician guidance in patients with significant renal impairment.

Elderly

Limited data are available in elderly patients; use with routine monitoring, as age-related hepatic or renal changes may be relevant.

Pediatric Patients

Safety and efficacy of Resmirom have not been established in pediatric patients.

The duration of treatment with Resmirom is determined by the treating physician based on clinical response, liver test monitoring, and periodic reassessment of liver fibrosis. Resmirom is generally intended for long-term use as part of an ongoing management plan for MASH/NASH with fibrosis, combined with continued diet and exercise; do not stop treatment without consulting a physician.

Thyroid hormone receptor-beta (THR-beta) selective agonist; hepatology/metabolic liver disease agent.

Resmetirom selectively activates thyroid hormone receptor-beta in the liver, increasing mitochondrial fatty acid oxidation and reducing hepatic fat accumulation, while having limited activity on thyroid hormone receptor-alpha (which predominates in the heart and bone), thereby aiming to reduce steatohepatitis and fibrosis with reduced risk of classic systemic thyrotoxic effects.

The safety and effectiveness of Resmirom have not been established in pediatric patients. Resmirom is not recommended for use in children or adolescents outside of a clinical trial setting until further data are available.