Fibrocon 100-MG Tablet

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

• For patients weighting <100 kg Fibrocon dose should be 60 mg once daily.
• For patients weighting >100 kg Fibrocon 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 Fibrocon adverse reactions. Concomitant use of Fibrocon with OATP1B1 or OATP1B3 inhibitors (e.g., Cyclosporine) is not recommended.

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

The common side effects of Fibrocon 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 Fibrocon. Monitoring of patient is required during treatment with Fibrocon for elevations in liver tests, for the development of liver-related adverse reactions and for sign & symptoms of hepatotoxicity. If hepatotoxicity is suspected, Fibrocon 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 Fibrocon 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 Fibrocon-treated patients. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated , If an acute gallbladder event is suspected, Fibrocon 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 Fibrocon, 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 Fibrocon 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 Fibrocon compared to younger adult patients.

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

Hepatic Impairment: Use of Fibrocon 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 Fibrocon. 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.