Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Ipsen Pharma, 65 quai Georges Gorse, 92100 Boulogne-Billancourt, France
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
The mechanism of action of odevixibat requires that the enterohepatic circulation of bile acids and bile salt transport into biliary canaliculi is preserved. Conditions, medications, or surgical procedures that impair either gastrointestinal motility, or enterohepatic circulation of bile acids, including bile salt transport to biliary canaliculi have the potential to reduce the efficacy of odevixibat.
Diarrhoea has been reported as a common adverse reaction when taking odevixibat. Diarrhoea may lead to dehydration. Patients should be monitored regularly to ensure adequate hydration during episodes of diarrhoea (see section 4.8).
An increase in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) has been observed on treatment with odevixibat (see section 4.8). Clinical relevance and long-term impact of these events is currently not known. Monitoring of liver function is recommended prior to initiating odevixibat and 6 weeks after initiation.
Patients with severe hepatic impairment (Child-Pugh C) have not been studied (see section 5.2). Periodic liver function tests should be considered for patients with severe hepatic impairment.
Assessment of fat-soluble vitamin (FSV) levels (Vitamins A, D, E) and international normalised ratio (INR) are recommended for all patients prior to initiating odevixibat, with monitoring per standard clinical practice. If FSV deficiency is diagnosed, supplemental therapy should be prescribed.
In clinical trials, decreased levels of fat-soluble vitamins were observed in some patients receiving odevixibat. Levels of fat-soluble vitamins should be monitored (see section 4.4).
Odevixibat is a substrate for the efflux transporter P-glycoprotein (P-gp). In adult healthy subjects, co- administration of the strong P-gp inhibitor itraconazole increased the plasma exposure of a single dose of odevixibat 7 200 mcg by approximately 50-60%. This increase is not considered clinically relevant. No other potentially relevant transporter-mediated interactions were identified in vitro (see section 5.2).
In vitro, odevixibat did not induce CYP enzymes (see section 5.2).
In in vitro studies, odevixibat was shown to be an inhibitor of CYP3A4/5 (see section 5.2).
In adult healthy subjects, concomitant use of odevixibat decreased the area under the curve (AUC) of oral midazolam (a CYP3A4 substrate) by 30% and 1-OH-midazolam exposure by less than 20%, which is not considered clinically relevant.
No interaction studies have been conducted with UDCA and rifampicin.
In an interaction study with a lipophilic combination oral contraceptive containing ethinyl estradiol (EE) (0.03 mg) and levonorgestrel (LVN) (0.15 mg) conducted in adult healthy females, concomitant use of odevixibat had no impact on the AUC of LVN and decreased the AUC of EE by 17%, which is not considered clinically relevant. Interaction studies with other lipophilic medicinal products have not been performed, therefore, an effect on the absorption of other fat-soluble medicinal products cannot be excluded.
Interaction studies have only been performed in adults. No differences are expected between the adult and paediatric populations.
Women of childbearing potential should use an effective method of contraception when treated with odevixibat.
There are no or limited data from the use of odevixibat in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Odevixibat is not recommended during pregnancy and in women of childbearing potential not using contraception.
It is unknown whether odevixibat or its metabolites are excreted in human milk. There is insufficient information on the excretion of odevixibat in animal milk (see section 5.3).
A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from odevixibat therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.
No fertility data are available in humans. Animal studies do not indicate any direct or indirect effects on fertility or reproduction (see section 5.3).
Odevixibat has no or negligible influence on the ability to drive and use machines.
The most commonly reported adverse reaction in ALGS patients treated with odevixibat in clinical trials was diarrhoea (11.5%).
Table 3 lists adverse reactions identified in patients with ALGS.
Adverse reactions are ranked according to system organ class and frequency grouping. Frequencies are defined using 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) and not known (cannot be estimated from the available data).
Table 3. Frequency of adverse reactions reported in patients with ALGS:
| MedDRA system organ class | Very common | Common |
|---|---|---|
| Gastrointestinal disorders | Diarrhoea* | abdominal pain*a, vomiting* |
| Hepatobiliary disorders | hepatic enzyme increasedb |
a Includes abdominal pain upper
b Includes hepatic enzyme increased, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased; see section 4.4.
* See section ‘Description of selected adverse reactions’.
Adverse reactions of diarrhoea occurred at a frequency of 11.5% in ALGS patients treated with odevixibat. Median time to onset of diarrhoea was 14.5 days and median duration was 4 days.
Clinically significant diarrhoea that persisted for 3 or more days without any other aetiology was reported in 5.8% of patients (see section 4.4). No treatment interruptions or discontinuations were reported for diarrhoea.
Adverse reactions of abdominal pain and vomiting were reported in 7.7% and 3.8% of patients, respectively; none were concurrent with adverse reactions of diarrhoea. Median time to onset of abdominal pain was 1.5 days and median duration was 6 days. For vomiting, median time to onset was 2.5 days and median duration was 13.5 days. With the exception of one treatment interruption for abdominal pain, there were no other treatment interruptions or discontinuations due to abdominal pain or vomiting.
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.
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