Odevixibat

There are no or limited data from the use of odevixibat in pregnant women. Animal studies have shown reproductive toxicity. 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.

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 breastfeeding 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.

Women of childbearing potential

Women of childbearing potential should use an effective method of contraception when treated with odevixibat. Since the uptake of lipophilic oral contraceptives may be affected by odevixibat, a barrier contraceptive method should be used.

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

Summary of the safety profile

The most commonly reported adverse reaction was diarrhoea reported in (7%) of patients.

Tabulated list of adverse reactions

The table lists adverse reactions identified in clinical trials in patients with PFIC aged between 4 months to 25 years of age (median 3 years 7 months).

Adverse reactions are ranked according to system organ class, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000) and not known (cannot be estimated from the available data).

Frequency of adverse reactions in PFIC patients:

^a Includes abdominal pain upper

Description of selected adverse reactions

Gastrointestinal adverse reactions

Gastrointestinal adverse reactions occurred at a frequency of 11% in patients treated with odevixibat. Adverse reactions of diarrhoea, abdominal pain and faeces soft were of short duration with most events ≤5 days in duration; median time to first onset was 16 days. All reports were mild to moderate in severity and non-serious. Two patients experienced an adverse reaction of clinically significant diarrhoea defined as diarrhoea that persisted for 21 or more days without any other aetiology, was severe in intensity, required hospitalisation or was considered an important medical event, or presented with concurrent dehydration requiring treatment with oral or intravenous rehydration and/or other treatment intervention. Treatment interruption was reported for diarrhoea in 4% of patients and discontinuation of odevixibat due to diarrhoea was reported in 1%.