RESILIVA 80

Indications

• Non-alcoholic fatty liver disease (NAFLD)
• Dyslipidaemia associated with thyroid hormone dysfunction

Dosage

Children: Refer to the BNF for Children for specific dosing information for pa

Adults: Refer to the BNF for specific dosing information for adults as it is not provided in the extracted text.

Mechanism of action

Resmetirom acts as a partial agonist of the thyroid hormone receptor-beta (THR-β), which is predominantly expressed in the liver. This action reduces intrahepatic triglycerides and promotes lipophagy and hepatic fatty acid β-oxidation. By stimulating THR-β, resmetirom addresses the metabolic disturbances associated with conditions like non-alcoholic fatty liver disease (NAFLD).

Pharmacodynamics

Resmetirom exhibits 83.8% of the maximum response compared to triiodothyronine (T3) at an EC50 of 0.21 µM for THR-β activation in vitro. For THR-α, it shows 48.6% efficacy relative to T3 with an EC50 of 3.74 µM. The drug decreases liver fat content and impacts the concentrations of free thyroxine (FT4), which is a prohormone. There are observations suggesting that resmetirom may facilitate the conversion of thyroxine (T4) to triiodothyronine (T3), although this remains inconclusive.

Pharmacokinetics

The pharmacokinetics of resmetirom have not been detailed in the provided data. However, as a thyroid hormone receptor agonist, it is likely to be absorbed, metabolized, and excreted in a manner consistent with other similar compounds. Further studies would provide more comprehensive information regarding its bioavailability, half-life, and elimination pathways.

Adverse effects

• Hypothyroidism
• Elevated liver enzymes
• Diarrhea
• Nausea
• Fatigue

Precautions

• Monitor liver function tests regularly during treatment.
• Use with caution in patients with a history of cardiovascular disease.
• Assess thyroid function prior to and during treatment.

Pregnancy

There are no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether resmetirom is excreted in human milk. Caution is advised when administered to nursing women.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets

Mechanism of action

Thyroid hormones, such as FT4 and free triiodothyronine (FT3), are key regulators of lipid metabolism in the liver. Thyroid hormone receptor-beta (THR-β) is the major form of the thyroid hormone receptor in the liver, and stimulation of this receptor reduces intrahepatic triglycerides. Many patients with non-alcoholic fatty liver disease (NAFLD) present with impaired thyroid function, such as hypothyroidism, rendering it a significant risk factor for NAFLD. Hypothyroidism has also been linked to dysregulated adipose tissue lipolysis and increased free fatty acid release from the adipose to the liver, promoting hepatic insulin resistance. Increased circulating levels of proinflammatory adipokines, which contribute to hepatic inflammation and fibrosis, may also be observed. Resmetirom is a partial agonist of THR-β that promotes lipophagy and hepatic fatty acid β-oxidation, thereby reducing liver fat. It is approximately 28 times more selective than FT3 for THR-β versus thyroid hormone receptor-alpha (THR-α), which is mainly expressed in the heart and bones.

Pharmacodynamics

Resmetirom is a partial agonist of the thyroid hormone receptor-beta (THR-β). Resmetirom produced 83.8% of the maximum response compared to triiodothyronine (T3), with an EC₅₀ of 0.21 µM in an in vitro functional assay for THR-β activation. The same functional assay for thyroid hormone receptor-alpha (THR-α) agonism showed 48.6% efficacy for resmetirom relative to T3, with an EC50 of 3.74 µM. Resmetirom decreases liver fat content and the concentrations of free thyroxine (FT4), which is a prohormone. Although it is inconclusive, there have been some reports in the literature suggesting that resmetirom may convert thyroxine (T4) to triiodothyronine (T3). It increases the concentrations of sex hormone-binding globulin.