Healthful Living Rx: MASH Clinical Perspectives

Gallbladder-Related Adverse Reactions Cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone) were observed more often in Rezdi‚ra-treated patients than in placebo-treated patients. The exposure-adjusted incidence rates (EAIRs) for these events were less than 1 per 100 person-years (PY) for all treatment arms. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an acute gallbladder event is suspected, interrupt treatment 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 Rezdi‚ra, which may increase the risk of adverse reactions related to these drugs. Dosage adjustment for certain statins is recommended. Monitor for statin-related adverse reactions including, but not limited to, elevation of liver tests, myopathy, The most common adverse reactions with Rezdi‚ra (reported in ≥5% of patients and higher compared to placebo) are diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness. Diarrhea and nausea were the most common causes of treatment discontinuation. DRUG INTERACTIONS Clinically Significant Interaction Eects of Strong or Moderate CYP2C8 Inhibitors on Rezdira • Concomitant use with strong CYP2C8 inhibitors (eg, gemfibrozil) is not recommended. Reduce Rezdi‚ra dosage if used concomitantly with a moderate CYP2C8 inhibitor (eg, clopidogrel). and rhabdomyolysis. ADVERSE REACTIONS

INDICATION AND IMPORTANT SAFETY INFORMATION INDICATION

Rezdi‚ra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitation of Use: Avoid use in patients with decompensated cirrhosis. WARNINGS AND PRECAUTIONS Hepatotoxicity Hepatotoxicity has been observed with the use of Rezdi‚ra. One patient developed substantial elevations of liver biochemistries that resolved when treatment was interrupted. Please see full Prescribing Information for more details on this specific case of Hepatotoxicity [see Warnings and Precautions (5.1)]. Monitor for elevations in liver tests, liver-related adverse reactions, and symptoms/signs of hepatotoxicity (eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, and/or eosinophilia [>5%]). If hepatotoxicity is suspected, discontinue Rezdi‚ra and monitor. If laboratory values return to baseline, weigh the potential risks against the benefits of restarting Rezdi‚ra. If laboratory values do not return to baseline, consider drug- induced autoimmune-like hepatitis (DI-ALH) or autoimmune liver disease in the evaluation of elevations in liver tests.

Please see Brief Summary on the following pages and full Prescribing Information at https://www.madrigalpharma.com/Rezdira-us-prescribing-information.

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