LYNAVOY Film-coated tablet Ref.[117086] Active ingredients: Linerixibat

Transaminase elevations

In clinical studies, treatment emergent transaminase elevations were observed in some patients receiving linerixibat (see section 4.8). It is recommended that baseline transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) levels are obtained prior to initiating treatment with linerixibat and transaminases monitored at a frequency aligned with standard clinical practice for PBC patients. For transaminase elevations, more frequent monitoring may be required. If transaminase elevations persist, weigh the potential risks against the benefit of continuing treatment.

Patients with hepatic impairment

No dose adjustment is required for patients with mild or moderate (Child-Pugh A or B) hepatic impairment (see section 5.2). Prior to initiation of treatment with linerixibat the patient's hepatic status should be assessed including whether the patient has liver decompensation or has had a prior decompensation event. No data are available for patients with severe hepatic impairment (Child-Pugh C). Use of linerixibat is not recommended in these patients or those at high risk of decompensation. If used, close monitoring is advised (see sections 4.2 and 5.2).

Diarrhoea

Diarrhoea has been reported as a very common adverse reaction when taking linerixibat (section 4.8). If diarrhoea occurs, advise patients to monitor for signs and symptoms of dehydration. Treatment with antidiarrheal medication may be required. Consider interrupting or discontinuing linerixibat treatment if diarrhoea persists.

Fat-soluble vitamin deficiency

Assessment of fat-soluble vitamin (FSV) levels (vitamins A, D, E and K) and international normalised ratio (INR) are recommended for all patients prior to initiating linerixibat, with monitoring per standard clinical practice. If FSV deficiency is diagnosed, supplemental therapy should be prescribed.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially 'sodium-free'.

Bile acid binding resins

Bile acid binding resins (such as colestyramine, colesevelam, or colestipol) may bind to other medicinal products, including linerixibat, in the gut when administered concurrently, and therefore may reduce the efficacy of linerixibat (see section 5.2). It is recommended that patients take Lynavoy at least 4 hours before or 4 hours after taking a bile acid binding resin (see section 4.2).

Ursodeoxycholic acid (UDCA)

UDCA can be coadministered with linerixibat, and no dose adjustments are required. In clinical studies with concomitant administration of UDCA and linerixibat no clinically relevant increases in ALP were observed. However, the overall plasma profile of UDCA and its conjugates was relevantly altered with concomitant administration of linerixibat. Clinical relevance of these changes are currently unclear. Patients should be monitored for changes in ALP during the initial treatment phases and periodically thereafter, aligned with standard clinical practice for PBC patients (see section 5.2).

Pregnancy

There are no or limited amount of data from the use of linerixibat in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Systemic absorption following oral administration of linerixibat in humans is minimal (see section 5.2). Therefore, foetal exposure to linerixibat is also expected to be minimal.

As a precautionary measure, it is preferable to avoid the use of Lynavoy during pregnancy.

Breast-feeding

It is unknown whether linerixibat is excreted in human milk.

Animal studies have shown excretion of linerixibat in milk; however, at the recommended clinical dose, neonatal exposure via breast milk is expected to be minimal (see section 5.3). No effects on the breastfed suckling child are anticipated since the systemic exposure of the breast-feeding woman to linerixibat is negligible. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Lynavoy therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.

Fertility

No fertility data are available in humans. Animal studies do not indicate any direct or indirect effects on fertility or reproduction at clinically relevant exposures (see section 5.3).

Lynavoy has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequently reported adverse reactions were diarrhoea (59%) and abdominal pain (23%).

Tabulated list of adverse reactions

The adverse reaction profile of linerixibat was evaluated in a pooled safety data set (Phase 3 GLISTEN and Phase 2b GLIMMER) including a total of 142 patients receiving linerixibat 40 mg twice daily orally for up to 24 weeks (see section 5.1). The majority of adverse reactions were mild or moderate.

Adverse reactions are listed below (Table 1) by MedDRA system organ class and frequency grouping. Frequencies are defined as: very common (≥1/10) and common (≥1/100 to <1/10).

Table 1. Adverse reactions reported in patients treated with Lynavoy:

Description of selected adverse reactions

Diarrhoea

In the pooled safety dataset, diarrhoea was observed in 59% of patients in the linerixibat treatment group. Discontinuation of treatment due to diarrhoea occurred in 4% of study patients in the linerixibat treatment group. Most events occurred within 1 week of initiating treatment, were mild in intensity, and most resolved during the study. None were serious. The majority of patients who experienced diarrhoea were able to continue linerixibat without treatment discontinuation or interruption. In some patients, diarrhoea persisted or recurred during treatment with linerixibat. Some patients received antidiarrhoeals (e.g., loperamide) to manage symptoms (see section 4.4).

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.

Not applicable.