Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

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. For this reason, e.g. patients with PFIC2 who have a complete absence or lack of function of Bile Salt Export Pump (BSEP) protein (i.e. patients with BSEP3 subtype of PFIC2) will not respond to odevixibat.

There are limited or no clinical data with odevixibat in PFIC subtypes other than 1 and 2.

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.
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).

In clinical trials, increased levels in liver function tests were observed in some patients receiving odevixibat. Assessment of liver function tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and total bilirubin) is recommended for all patients prior to initiating Bylvay, with monitoring per standard clinical practice.

For patients with liver function test elevations, more frequent monitoring should be considered.

Assessment of fat-soluble vitamin levels (Vitamins A, D, E) and international normalised ratio (INR) are recommended for all patients prior to initiating Bylvay, with monitoring per standard clinical practice.

Treatment with odevixibat may impact the absorption of fat-soluble medicinal products (see section 4.5).

Patients enrolled in the ALGS trial had abnormal liver tests at baseline. In Trial 3 in ALGS patients, treatment-emergent elevations or worsening in liver tests relative to baseline values were observed during the trial. Most abnormalities included elevation in ALT or AST. One patient interrupted treatment for 40 days; none of the patients in Trial 3 permanently discontinued treatment due to liver test abnormalities.

In Trial 3, diarrhea in ALGS patients was reported in 1 placebo-treated patient (6%) and in 10 (29%) BYLVAY-treated patients [see section 4.8]. No patients interrupted or permanently discontinued BYLVAY due to diarrhea.

Effects on Driving

4.7    Effects on ability to drive and use machines

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