Resilivabd Prescribe information

PHARMACOLOGY

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 37.4 μM. THR-β is the major form of THR in the liver, and stimulation of THR-β in the liver reduces intrahepatic triglycerides, whereas action of thyroid hormone outside the liver, including on the heart and bone, are largely mediated through THR-α.

INDICATION

Resmetirom is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

DOSAGE & ADMINISTRATION

The recommended dose of Resmetirom is based on actual body weight. For patients weighing:

  • ≥100 kg, the recommended dose is 100 mg orally once daily.

     

  • <100 kg, the recommended dose is 80 mg orally once daily.

The recommended dose of Resmetirom with moderate CYP2C8 inhibitors is:

  • For patients weighing:

     

    • ≥100 kg, the recommended dose is 80 mg orally once daily.

       

    • <100 kg, the recommended dose is 60 mg orally once daily.

Resmetirom can be administered with or without food.

CONTRAINDICATIONS

  • None.

     

WARNINGS & PRECAUTION

Hepatotoxicity
 Hepatotoxicity has been observed with use of Resmetirom. Monitoring of patients is required during treatment with Resmetirom for elevations in liver tests, for development of liver-related adverse reactions and for signs & symptoms of hepatotoxicity. If hepatotoxicity is suspected, Resmetirom should be discontinued and monitoring of the patient should be continued. If laboratory values return to baseline, the benefits and risks of continuing Resmetirom treatment should be considered. If laboratory values do not return to baseline, DILI-AIH or autoimmune liver disease must be considered in the evaluation of elevations in liver tests.

Gallbladder-Related Adverse Reactions
 Gallbladder-related adverse reactions, acute cholecystitis, and obstructive pancreatitis (gallstone) were observed in patients treated with Resmetirom. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. In case acute gallbladder or gallstone-related pancreatitis and obstructive pancreatitis are suspected, Resmetirom treatment should be interrupted until the event is resolved.

Drug Interaction with Certain Statins
 An increase in exposure of Atorvastatin, Pravastatin, Rosuvastatin and Simvastatin was observed when concomitant use with Resmetirom. Resmetirom may increase the risk of adverse reactions related to these statins. Dose adjustment for certain statins is recommended.

SIDE EFFECTS

Among the common side effects of Resmetirom are:

  • Diarrhea
  • Nausea
  • Abdominal pain
  • Dizziness
  • Pruritus
  • Constipation

DRUG INTERACTIONS

Effects of Other Drugs on Resmetirom:

  1. Strong or Moderate CYP2C8 Inhibitors: Concomitant use of Resmetirom with strong or moderate CYP2C8 inhibitors can increase the risk of Resmetirom adverse reactions. Concomitant use of Resmetirom with strong CYP2C8 inhibitors (e.g., Gemfibrozil) is not recommended. Resmetirom doses should be reduced if used concomitantly with a moderate CYP2C8 inhibitor (e.g., Clopidogrel).
  • Organic Anion-Transporting Polypeptides (OATP) 1B1 and OATP1B3 Inhibitors: Concomitant use with OATP1B1 and OATP1B3 inhibitors may increase the risk of Resmetirom adverse reactions. Concomitant use of Resmetirom with OATP1B1 or OATP1B3 inhibitors (e.g., Cyclosporine) is not recommended.

Effects of Resmetirom on Other Drugs:

  • Statins (Atorvastatin, Pravastatin, Rosuvastatin, or Simvastatin): Resmetirom increases plasma concentrations of some statins (Atorvastatin, Pravastatin, Rosuvastatin and Simvastatin), which may increase the risk of adverse reactions related to these drugs. Dose adjustment of statins is recommended. Rosuvastatin and Simvastatin: Maximum daily statin dose should be 20 mg. Pravastatin and Atorvastatin: Maximum daily statin dose should be 40 mg.

     

  • CYP2C8 Substrates: Resmetirom increases exposure of CYP2C8 substrates (e.g., Pioglitazone), which may increase the risk of adverse reactions related to these substrates. Patients should be monitored more frequently for substrate-related adverse reactions if Resmetirom is co-administered with CYP2C8 substrates where minimal concentration changes may lead to serious adverse reactions.

USE IN SPECIFIC POPULATIONS

Pregnancy
 There are no available data on Resmetirom use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation
 There is no information regarding the presence of Resmetirom in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Resmetirom and any potential adverse effects on the breastfed infant from Resmetirom or from the underlying maternal condition.

Pediatric Use
 The safety and effectiveness of Resmetirom have not been established in pediatric patients.

Geriatric Use
 No overall differences in effectiveness but numerically higher incidence of adverse reactions have been observed in patients 65 years of age and older when compared with Resmetirom compared to younger adult patients.

Renal Impairment
 The recommended dose of Resmetirom in patients with mild or moderate renal impairment is the same as the dose in patients with normal kidney function. Resmetirom has not been studied in patients with severe renal impairment.

Hepatic Impairment
 Use of Resmetirom in patients with decompensated cirrhosis (consistent with moderate to severe hepatic impairment) should be avoided. Moderate or severe hepatic impairment (Child-Pugh Class B or C) may increase the risk of adverse reactions of Resmetirom. No dose adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Class A).

PHARMACEUTICAL INFORMATION

Storage Condition
 Store below 30°C, in a cool and dry place. Keep away from direct sunlight and reach of children.

How Supplied

  • RESILIVA 80 mg tablet: Each HDPE container contains 30 film coated tablets; a silica gel desiccant and polyester coil within a child-resistant closure.

     

  • RESILIVA 100 mg tablet: Each HDPE container contains 30 film coated tablets; a silica gel desiccant and polyester coil within a child-resistant closure.

Manufactured by
 Everest Pharmaceuticals Ltd.
 BSCIC I/A, Kawchar, Narayanganj, Bangladesh
 🌐 www.everestpharmabd.com