Chenodeoxycholic acid Leadiant (previously Chenodeoxycholic acid sigma-tau) · 4.3 Contraindications · 1

HOS-217173 · has-adverse-reaction-information · PDF-Seite 5

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. 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 Transaminases increased not known Jaundice not known 5 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. Due to the rarity of CTX, the available literature is not sufficient to detect a difference in the safety of chenodeoxycholi

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217169 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-217168 · has-indication-information · PDF-Seite 2

Chenodeoxycholic acid is indicated for the treatment of inborn errors of primary bile acid synthesis due to sterol 27-hydroxylase deficiency (presenting as cerebrotendinous xanthomatosis (CTX)) in infants, children and adolescents aged 1 month to 18 years and adults.

HOS-217171 · has-interaction-information · PDF-Seite 4

In patients with CTX, no interaction studies with chenodeoxycholic acid and concomitantly administered medicinal products have been performed. Colestipol and antacid medicinal products Chenodeoxycholic acid should not be administered together with colestipol or antacid medicinal products containing aluminium hydroxide and/or smectite (aluminium oxide) since these preparations bind the active substance of chenodeoxycholic acid in the intestine and thus prevent its reabsorption and efficacy. If it is necessary to take a medicinal product containing one of these active substances it should be taken either 2 hours before or after taking chenodeoxycholic acid. Colestyramine Chenodeoxycholic acid should not be administered together with colestyramine as it binds chenodeoxycholic acid in the intestine and thus prevents its reabsorption and efficacy. If it is necessary to take colestyramine then chenodeoxycholic acid should be taken either one hour before colestyramine or 4-6 hours after. Ciclosporin and sirolimus Ciclosporin has been shown to reduce the synthesis of chenodeoxycholic acid by inhibition of CYP27A1 and increasing the activity of HMG CoA reductase. A similar effect on CYP27A1, albeit at higher doses, is also seen with sirolimus. Co-administration of chenodeoxycholic acid with ciclosporin or sirolimus should be avoided. If administration of ciclosporin or sirolimus is considered necessary, serum and urine bile alcohol levels should be closely monitored and the chenodeoxycholic acid dose adjusted accordingly. Phenobarbital Concomitant administration of chenodeoxycholic acid with phenobarbital increases HMG CoA reductase and thus counteracts one of the pharmacodynamics effects of chenodeoxycholic acid in CTX. If administration of phenobarbital is considered necessary, serum and urine bile alcohol levels should be closely monitored and the chenodeoxycholic acid dose adjusted accordingly. Oral contraceptives The administration of oral contraceptives reduces the pool size of chenodeoxycholic acid. Oral contraceptives therefore may worsen the underlying deficiency and counteract the effectiveness of chenodeoxycholic acid in CTX. Co-administration with oral contraceptives is not recommended. 4

HOS-217172 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential Women of childbearing potential should use an effective method of contraception. The use of oral contraceptives is not recommended in patients taking chenodeoxycholic acid, see section 4.5 for further details. Pregnancy Patients with CTX and high cholestanol have been shown to have adverse outcomes during pregnancy. Two intrauterine deaths in a mother with CTX have been reported in the literature. Two pregnancies in mothers with CTX resulted in premature infants with evidence of intrauterine growth retardation also reported in the literature. There are no or limited amount of data from the use of chenodeoxycholic acid in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Chenodeoxycholic acid is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding It is unknown whether chenodeoxycholic acid/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from chenodeoxycholic acid therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman Fertility Chenodeoxycholic acid is an endogenous bile acid used for replacement therapy and it is anticipated to have no effects on fertility at therapeutic doses.

HOS-217170 · has-warning-information · PDF-Seite 3

Monitoring After the initiation period, cholestanol, urine bile alcohols and liver function should be determined annually, at a minimum, and the dose adjusted accordingly (see section 4.2). Additional or more frequent investigations may need to be undertaken to monitor therapy during periods of fast growth, concomitant disease and pregnancy (see section 4.6). Co-administration of chenodeoxycholic acid with other medicinal products Co-administration with ciclosporin, sirolimus, phenobarital is not recommended, see section 4.5 for further details. Colestipol or antacid medicinal products containing aluminium hydroxide and/or smectite should be taken either 2 hours before or after taking chenodeoxycholic acid, see section 4.5 for further details. 3 Chenodeoxycholic acid should be taken either one hour before cholestyramine or 4-6 hours after, see section 4.5 for further details. Co-administration with oral contraceptives is not recommended, see section 4.5 for further details. Women of childbearing potential should use an effective method of contraception, see section 4.6 for further details.