Orphacol

HOS-155067 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Due to the rarity of the diseases, the information about the most serious and/or most frequently occurring adverse reactions is limited. Diarrhoea, increased transaminases and pruritus have been associated with overdosage and disappeared after dose reduction. Development of gallstones associated with long-term treatment have been reported in very limited number of patients. Tabulated list of adverse reactions The following table lists adverse reactions reported in the literature under treatment with cholic acid. The frequency of these reactions is not known (cannot be estimated from the available data). MedDRA System Organ Class Adverse reaction Gastrointestinal disorders Diarrhoea Hepatobiliary disorders Transaminases increased Gallstones Skin and subcutaneous tissue disorders Pruritus Description of selected adverse reactions The development of pruritus and/or diarrhoea has been observed during treatment with Orphacol. These reactions abated after dose reduction and are suggestive of overdose. Patients presenting with pruritus and/or persistent diarrhoea should be investigated for a potential overdose by a serum and/or urine bile acid assay (see section 4.9). Gallstones have been reported after long-term therapy. Paediatric population The presented safety information is derived principally from paediatric patients. The available literature is not sufficient to detect a difference in the safety of cholic acid within paediatric age groups or between paediatric patients and adults. Other special populations Please refer to section 4.2 for use of Orphacol in special populations. 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

HOS-155063 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Concomitant use of phenobarbital and primidone with cholic acid (see section 4.5).

HOS-155062 · has-indication-information · PDF-Seite 2

Orphacol is indicated for the treatment of inborn errors in primary bile acid synthesis due to 3β-Hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-Oxosteroid-5β-reductase deficiency in infants, children and adolescents aged 1 month to 18 years and adults.

HOS-155065 · has-interaction-information · PDF-Seite 5

Phenobarbital and primidone, which is partially metabolized in phenobarbital, antagonise the effect of cholic acid. Use of phenobarbital or primidone in patients with 3β-Hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-Oxosteroid-5β-reductase deficiency treated with cholic acid is contraindicated (see section 4.3). Alternative treatments should be used. Ciclosporin alters the pharmacokinetics of cholic acid by inhibition of the hepatic uptake and hepatobiliary secretion of bile acids, as well as its pharmacodynamics by inhibition of cholesterol 7α-hydroxylase. Co-administration should be avoided. If administration of ciclosporin is considered necessary, serum and urine bile acid levels should be closely monitored and the cholic acid dose adjusted accordingly. Bile acid sequestrants (cholestyramine, colestipol, colesevelam) and certain antacids (e.g. aluminium hydroxide) bind bile acids and lead to their elimination. Administration of these medicinal products is expected to reduce the effect of cholic acid. The dose of bile acid sequestrants or antacids must be separated from the dose of cholic acid by an interval of 5 hours, regardless of which medicinal product is administered first. Ursodeoxycholic acid competitively inhibits absorption of other bile acids, including cholic acid, and replaces them in the enterohepatic pool, reducing the effectiveness of negative feedback inhibition on bile acid synthesis provided by oral cholic acid. For patients who are prescribed a combination of ursodeoxycholic acid and cholic acid in single doses, the administration of both medicinal products should be separated: one product should be given in the morning and the other product should be given in the evening, regardless of which medicinal product is given first. For those patients, who are prescribed a combination of ursodeoxycholic acid and cholic acid, in divided doses of cholic acid and/or ursodeoxycholic acid over the day, the administration of these medicinal products should be separated by several hours. The effect of food on the bioavailability of cholic acid has not been studied. There is a theoretical possibility that administration with food may increase cholic acid bioavailability and improve tolerability.

HOS-155066 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential There is no need for contraceptive measures in women of childbearing potential treated with cholic acid or their partners. Women of childbearing potential should conduct a pregnancy test as soon as a pregnancy is suspected. Pregnancy There is a limited amount of data (less than 20 pregnancy outcomes) from the use of cholic acid in pregnant women. The exposed pregnancies showed no adverse reactions to cholic acid and resulted in normal, healthy children. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). It is extremely important that pregnant women continue their therapy during pregnancy. As a precautionary measure, pregnant women and their unborn children should be closely monitored. Breastfeeding 5 Cholic acid and its metabolites are excreted in human milk, but at therapeutic doses of Orphacol, no effects on the breastfed newborns/infants are anticipated. Orphacol can be used during breast-feeding. Fertility No data on the effects of cholic acid on fertility are available. At therapeutic doses, no effect on fertility is anticipated.

HOS-155064 · has-warning-information · PDF-Seite 4

Cases of severe hepatotoxicity, including cases with fatal outcome, have been reported, with the use of cholic acid. Treatment with cholic acid in patients with pre-existing hepatic impairment should be given under close monitoring and, for all patients, should be stopped if abnormal hepatocellular function, as measured by prothrombin time, does not improve within 3 months of the initiation of cholic acid treatment. A concomitant decrease of urine total bile acids should be observed. Treatment should be stopped earlier if there are clear indicators of severe hepatic failure. Familial hypertriglyceridemia Patients with newly diagnosed or a family history of familial hypertriglyceridaemia may have poor absorption of cholic acid from the intestine. The dose of cholic acid in such patients should be established and adjusted as described, but an elevated dose, notably higher than the 500 mg daily limit for adult patients, may be required. Excipients 4 Orphacol capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.