Instructions for Livdelzi (Seladelpar)

1. Name:Livdelzi, Seladelpar

2. Indications:

Livdelzi (Seladelpar) is indicated in combination with ursodeoxycholic acid (UDCA) for the treatment of adults with primary cholangitis (PBC) who have not responded to UDCA, or for the treatment of patients who cannot tolerate UDCA. This indication was approved under accelerated approval based on alkaline phosphatase (ALP) reduction. Improved survival or prevention of hepatic decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and characterization of clinical benefit in confirmatory trials.

3. Usage and dosage:

1. Recommended dosage and usage: The recommended dosage of Livdelzi is 10 mg once daily. Take Livdelzi with or without food.

2. Modification of dosing of bile acid sequestrants: Take Livdelzi at least 4 hours before or 4 hours after taking bile acid sequestrants, or as long as possible.

4. Adverse reactions:

In clinical studies of Livdelzi, the most common adverse reactions included headache, abdominal pain, nausea, bloating and dizziness.

5. Supply and storage:

Livdelzi is available in capsule form in 10 mg doses and may be stored at 20°C to 25°C (68°F to 77°F); tolerances are 15°C to 30°C (59°F to 86°F).

6. Taboo:

Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

7. Mechanism of action:

The ingredient in Livdelzi, Seladelpar, is a peroxisome proliferator-activated receptor (PPAR)-delta agonist. However, the mechanism by which Seladelpar exerts its therapeutic effect on PBC patients is unclear. Pharmacological activities potentially relevant to therapeutic efficacy include inhibition of bile acid synthesis through activation of PPARδ, a nuclear receptor expressed in most tissues including the liver. Published studies have shown that activation of PPARδ by Seladelpar reduces bile acid synthesis through fibroblast growth factor 21 (FGF21)-dependent downregulation of CYP7A1, a key enzyme in the synthesis of bile acids from cholesterol.

8. Overdose:

Patients with PBC who received 5 times the recommended dose or 20 times the recommended dose of Livdelzi experienced elevated liver transaminases, myalgia, and/or elevated creatine phosphokinase, which resolved after discontinuation of Livdelzi.

For overdoseThere is no specific treatment for Livdelzi. Where appropriate, general supportive care of the patient is indicated. If necessary, unabsorbed drug should be eliminated by vomiting or gastric lavage; usual precautions should be followed to maintain the airway. Because seladelpar is highly bound to plasma proteins, hemodialysis should not be considered.