Livdelzi

/ Gilead

The recommended dose of seladelpar is 10 mg once daily.
Missed dose
If a dose of seladelpar is missed, the patient should take the subsequent dose at the next scheduled time point. A double dose should not be taken to make up for the missed dose.
Hepatic impairment
No dose adjustment is required in PBC patients with mild hepatic impairment (Child-Pugh A). Safety and efficacy of seladelpar have not been established in PBC patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. Use of seladelpar is not recommended in patients with severe hepatic impairment and in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).
Monitor patients with cirrhosis for evidence of decompensation.
Consider discontinuing seladelpar if the patient progresses to moderate or severe hepatic impairment (Child-Pugh B or C)

Treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA.

Hypersensitivity to the active substance or to any of the excipients
Special Precautions:

Liver test abnormalities
Dose dependent increases in serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) have been observed in patients receiving higher doses of seladelpar. Obtain baseline clinical and laboratory assessments at initiation of treatment with seladelpar and monitor thereafter according to routine clinical practice. Consider temporary interruption of seladelpar treatment if liver tests worsen, or the patient develops signs and symptoms consistent with liver dysfunction. Consider permanent discontinuation if liver tests worsen again after restarting seladelpar.
Biliary Obstruction
Avoid use of seladelpar in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt seladelpar and treat as clinically indicated.
Co-administration of other medicinal products
Co-administration of probenecid with seladelpar is not recommended

Very Common: Abdominal pain
Common: Headache, Nausea, Abdominal distension

Effect of other medicinal products on seladelpar
Probenecid
Concomitant administration of seladelpar with probenecid (an OAT1, OAT3 and OATP1B1-inhibitor) is not recommended.
In a dedicated clinical drug interaction study, seladelpar area under the curve from zero to time infinity (AUC0-inf) increased by 2-fold and maximum serum concentration (Cmax) by 4.69-fold following concomitant use of a single 10 mg seladelpar dose with 500 mg probenecid in healthy subjects.
Inhibitors of drug transporters
Concomitant administration of seladelpar with dual or multiple clinical inhibitors of drugs transporters including BCRP, OATP1B1, OATP1B3 and OAT3 (e.g cyclosporine) may result in an increase of seladelpar exposure. When seladelpar is concomitantly administered with dual or multiple clinical inhibitors of drugs transporters including BCRP, OATP1B1, OATP1B3, and OAT3, patients should be closely monitored for adverse effects.
In a dedicated clinical drug interaction study, seladelpar AUC0-inf increased by 2.1-fold and Cmax by 2.9-fold following concomitant use of a single 10 mg seladelpar dose with 600 mg cyclosporine (a BCRP, OATP1B1, OATP1B3 and CYP3A4 inhibitor) in healthy subjects.
CYP2C9 and CYP3A4 inhibitors
Seladelpar is primarily metabolized in vitro by CYP2C9 and to a lesser extent by CYP2C8 and CYP3A4. Concomitant administration of seladelpar with medicines that are strong CYP2C9 inhibitors, or dual moderate CYP2C9 and moderate-to-strong CYP3A4 inhibitors may result in an increase in seladelpar exposure. When seladelpar is concomitantly administered with medicinal products that are strong CYP2C9 inhibitors, or dual moderate CYP2C9 and moderate to strong CYP3A4 inhibitors (e.g. fluconazole, mifepristone), patients should be closely monitored for adverse effects.
CYP2C9 inducers and strong CYP3A4 inducers
Concomitant administration of seladelpar with medicines that are CYP2C9 inducers and strong CYP3A4 inducers (e.g. rifampicin, a strong CYP3A4 and moderate CYP2C9 inducer) can decrease seladelpar exposure. When seladelpar is concomitantly administered with medicinal products that are CYP2C9 inducers and strong CYP3A4 inducers, patients should be monitored for a potential reduction in efficacy.
Bile acid binding resins
Bile acid binding resins such as cholestyramine, colestipol, or colesevelam, may reduce the absorption of other medicinal products administered concurrently. Patients should take seladelpar at least 4 hours before or 4 hours after taking a bile acid binding resin.
See prescribing information for full details.

Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of seladelpar in pregnant women. As a precautionary measure, it is preferable to avoid the use of seladelpar during pregnancy.
Lactation: It is unknown whether seladelpar or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from seladelpar therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

PBC patients who received 5 times the recommended dose or 20 times the recommended dose of seladelpar experienced an increase in liver transaminases, muscle pain, and/or elevations in creatine phosphokinase, which resolved upon seladelpar discontinuation. Dose dependent increases in serum creatinine were also observed.
There is no specific treatment for overdose with seladelpar. General supportive care of the patient is indicated, as appropriate. If indicated, elimination of unabsorbed medicinal product should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because seladelpar is highly bound to plasma proteins, haemodialysis should not be considered.