Adverse reactions : תופעות לוואי

4.8    Undesirable effects

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 (≥ 1/1 000 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 in PFIC patients
MedDRA system organ class       Common
Gastrointestinal disorders      diarrhoea,
abdominal paina,
diarrhoea haemorrhagic,
faeces soft
Hepatobiliary disorders         hepatomegaly 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 Bylvay.
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 (see section 4.4). Treatment interruption was reported for diarrhoea in 4% of patients and discontinuation of Bylvay due to diarrhoea was reported in 1%.
ALGS Clinical Studies
Trial 3 is a randomized, double-blind, placebo-controlled, 24-week study of a single dose level of BYLVAY (120 mcg/kg) administered once daily [see section 5.1]. Fifty-two patients were randomized (2:1) to receive one of the following:
• BYLVAY 120 mcg/kg/day (n=35), or
• Placebo (n=17).

Table 5 summarizes the frequency of adverse reactions in patients with ALGS, reported in ≥5% and at a rate greater than placebo in patients treated with BYLVAY in Trial 3. No patients discontinued study treatment due to an adverse reaction. The most common adverse reactions observed in Trial 3 included diarrhea, abdominal pain, hematoma, and decreased weight.


Table 5. Common Adverse Reactionsa from a Clinical Study of BYLVAY in Patients with Alagille Syndrome (Trial 3)
Placebo            BYLVAY 120 mcg/kg/day
N=17                     N=35
Adverse Reaction                                    n (%)                    n (%) Diarrhea                                           1 (6%)                  10 (29%) Abdominal Pain                                     1 (6%)                   5 (14%) Hematoma                                               0                     3 (9%) Weight decreased                                       0                     2 (6%) Adverse reactions that occurred in ≥5% of BYLVAY-treated patients a


Trial 4 is a 72-week, open-label extension study in 49 pediatric patients with ALGS aged 1 to 15 years. BYLVAY 120 mcg/kg/day was administered once daily. Treatment-emergent adverse 
reactions were similar to those observed in Trial 3. The most common reason for BYLVAY treatment interruption was gastrointestinal disorders, including diarrhea and abdominal pain .


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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il