Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Adverse reactions in patients (both adults and children) receiving chenodeoxycholic acid are generally mild to moderate in severity; the main reactions observed are given in the table below. The events were transitory and did not interfere with the therapy.

Tabulated list of adverse reactions
Adverse reactions are ranked according to MedDRA 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), not known (cannot be estimated from the available data).

MedDRA system organ class           Preferred term                      Frequency Gastrointestinal disorders          Constipation                        not known Hepatobiliary disorders             Hepatic adverse reactions           not known 
Description of selected adverse reactions
In two non-interventional studies with chenodeoxycholic acid a total of three adverse reactions were reported in three out of 63 patients (safety population). The three adverse reactions were all non- serious. One case of mild intermittent constipation occurred in an adult and another instance occurred in a child. One case of hepatic adverse reactions occurred in a two week old infant diagnosed with CTX and is discussed in the section below.

Paediatric population
In two-non interventional studies with chenodeoxycholic acid, a total of 14 paediatric patients with CTX were treated with chenodeoxycholic acid : 1 infant (0 to < 2 years), 6 children (2 to < 12 years) and 7 adolescents (12 to < 18 years). All paediatric patients received 15 mg/kg/day as their starting dose.

The only infant enrolled presented with raised liver function tests within six weeks of treatment start.
The infant’s liver function normalised upon temporarily stopping treatment with chenodeoxycholic acid. Chenodeoxycholic acid supplementation was re-started and maintained at a lower dose of 5 mg/kg/day with no further complications.
This case of hepatic adverse reactions in an infant presented with multiple confounders, such as concomitant parechovirus infection, co-administration of medicinal products known to affect liver function (acyclovir and phenobarbital) and presence of hyperbilirubinemia at birth.

The presented safety information for hepatic adverse reactions is derived from paediatric patients. Due to the rarity of CTX, the available literature is not sufficient to detect a difference in the safety of chenodeoxycholic acid within paediatric age groups or between paediatric patients and adults.

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