Renash Tablet

Renash tablet 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).

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 pM. THR-p is the major form of THR in the liver, and stimulation of THR-β in the liver reduces intrahepatic triglycerides.

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

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

Resmetirom can be administered with or without food.

Effects of Other Drugs on Renash: Strong or Moderate CYP2C8 Inhibitors: Concomitant use of Renash with a strong or moderate CYP2C8 inhibitor can increase the risk of Renash adverse reactions. Concomitant use of Renash with strong CYP2C8 inhibitors (e.g., Gemfibrozil) is not recommended. If used concomitantly with a moderate CYP2C8 inhibitor (e.g., Clopidogrel) Renash dose should be reduced, as:

• For patients weighting <100 kg Renash dose should be 60 mg once daily.
• For patients weighting >100 kg Renash dose should be 80 mg once daily.

Organic Anion- Transporting Polypeptides (OATP) 1B1 and OATP1B3 Inhibitors: Concomitant use with OATP1B1 and OATP1B3 inhibitors may increase the risk of Renash adverse reactions. Concomitant use of Renash with OATP1B1 or OATP1B3 inhibitors (e.g., Cyclosporine) is not recommended.

Effects of Renash on Other Drugs: Statins (Atorvastatin, Pravastatin, Rosuvastatin, or Simvastatin): Renash 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: Renash 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 Renash is co-administered with CYP2C8 substrates where minimal concentration changes may lead to serious adverse reactions.

The common side effects of Renash are: Diarrhea, Nausea, Vomiting, Abdominal pain, Dizziness, Pruritus, Constipation.

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 or animal milk, the effects on the breast-fed 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.

Hepatotoxicity: Hepatotoxicity has been observed with use of Renash. Monitoring of patient is required during treatment with Renash for elevations in liver tests, for the development of liver-related adverse reactions and for sign & symptoms of hepatotoxicity. If hepatotoxicity is suspected, Renash should be discontinued and monitoring of the patient should be continued. If laboratory values return to baseline, the potential risks against the benefits of restarting Renash should be considered. If laboratory values do not return to baseline, DI-ALH or autoimmune liver disease should be considered in the evaluation of elevations in liver tests.

Gallbladder-Related Adverse Reactions: In clinical trials, cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone) were observed in Renash-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated , If an acute gallbladder event is suspected, Renash 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 concomitantly administered with Renash, which may increase the risk of adverse reactions related to these drugs. Dosage adjustment for certain statins is recommended.

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

Geriatric Use: No overall differences in effectiveness but numerically higher incidence of advers reactions have been observed in patients 65 years of age and older who received Renash compared to younger adult patients.

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

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

Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.