Lyvdelzi (previously Seladelpar Gilead) · 4.4 Special warnings and precautions for use · 1

HOS-287275 · has-adverse-reaction-information · PDF-Seite 5

Summary of safety profile Based on clinical trial experience, the most frequently reported adverse reactions were abdominal pain (11.1%), headache (7.2%), nausea (6.5%) and abdominal distension (3.9%). These adverse reactions were non-serious and did not lead to discontinuation of seladelpar. Tabulated list of adverse reactions The frequencies of the adverse drug reactions provided in the table below are based on pooled data from the RESPONSE and ENHANCE trials unless otherwise stated. Frequencies are defined according to the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data). Table 1: Adverse drug reactions reported in clinical trials in patients treated with seladelpar System Organ Class Very Common Common Nervous System Disorders Headache Gastrointestinal Disorders Abdominal pain a Nausea Abdominal distension a Includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 5

HOS-287271 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-287270 · has-indication-information · PDF-Seite 2

Lyvdelzi is indicated for the 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.

HOS-287273 · has-interaction-information · PDF-Seite 3

Effect of other medicinal products on seladelpar Probenecid Concomitant administration of seladelpar with probenecid (an OAT1, OAT3 and OATP1B1-inhibitor) is not recommended (see section 4.4). 3 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. In a dedicated clinical drug interaction study, seladelpar AUC0-inf increased by 2.4-fold and Cmax by 1.4-fold following concomitant use of a single 10 mg seladelpar dose with 400 mg fluconazole (moderate CYP2C9 and CYP3A4 inhibitor) in healthy subjects. 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 induc

Auszug; vollständigen Abschnitt im Original lesen.

HOS-287274 · has-pregnancy-information · PDF-Seite 4

Pregnancy There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of seladelpar in pregnant women. 4 Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant exposure levels (see section 5.3). As a precautionary measure, it is preferable to avoid the use of seladelpar during pregnancy. Breast-feeding 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. Fertility No human data on the effect of seladelpar on fertility are available. Animal studies do not indicate any direct or indirect effects on fertility or the ability to reproduce.

HOS-287272 · has-warning-information · PDF-Seite 3

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 (see section 4.9). 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 (see section 4.5). Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per hard capsule, that is to say essentially ‘sodium-free’.