Chenodeoxycholic acid Leadiant

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Chenodeoxycholic acid Leadiant 250 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each hard capsule contains 250 mg of chenodeoxycholic acid. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule 
 
Size 0 capsule, 21.7 mm in length with a yellow body and orange cap, containing a white, compressed 
powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
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.  
 
4.2 Posology and method of administration 
 
Treatment must be initiated and monitored by physicians experienced in the management of CTX or 
inborn errors of primary bile acid synthesis. 
 
During the initiation of therapy and dose adjustment, serum cholestanol levels and/or urine bile 
alcohols should be monitored every 3 months till metabolic control and then annually. The lowest dose 
of chenodeoxycholic acid that effectively reduces the serum cholestanol and/or urine bile alcohols 
levels to within the normal range should be chosen. Liver function should also be monitored. 
Concurrent elevation of liver enzymes above normal levels may indicate overdose. After the initiation 
period, cholestanol, urine bile alcohols and liver function should be determined annually, at a 
minimum, and the dose adjusted accordingly. 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). 
 
In case of persistent lack of therapeutic response to chenodeoxycholic acid monotherapy, other 
treatment options should be considered. 
 
Posology 
Adults 
The starting dosage in adults is 750 mg/day, in three divided doses provided that it is sufficient to 
normalise serum cholestanol and/or urine bile alcohols. The daily dose can be subsequently increased 



3 

in 250 mg increments to a maximum of 1000 mg/ day if the serum cholestanol and/or urine bile 
alcohols remain elevated.   
 
Paediatric population (1 month -18 years) 
The starting dose in children is 5 mg/kg/day in three divided doses. Where the dose calculated is not a 
multiple of 250 mg, the nearest dose below the maximum of 15 mg/kg/day should be selected, 
provided that is sufficient to normalise serum cholestanol and/or urine bile alcohols.   
 
Neonates less than one month of age 
The safety and efficacy in neonates less than one month of age has not been established.  Limited 
safety data are available (see section 4.8). 
 
Special populations 
Elderly patients (≥ 65 years) 
Dose adjustment is not necessary. 
 
Renal impairment 
No data are available for patients with renal impairment. However, these patients should be carefully 
monitored and the dose titrated individually. 
 
Hepatic impairment 
No data are available for patients with hepatic impairment. However, these patients should be 
carefully monitored and the dose titrated individually. 
 
Method of administration  
Chenodeoxycholic acid capsules can be taken without regards to food. The hard capsules should be 
taken whole with sufficient water at approximately the same time each day. For infants and children 
who cannot swallow capsules, the capsules may be carefully opened and the content added to sodium 
bicarbonate solution 8.4%, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Monitoring 
After the initiation period, cholestanol, urine bile alcohols and liver function should be determined 
annually, at a minimum, and the dose adjusted accordingly. 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). 
 
Effects 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. 
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.  
 
4.5 Interaction with other medicinal products and other forms of interaction 



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. 
 
4.6 Fertility, pregnancy and lactation 
 
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.  
 



5 

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. 
 
4.7 Effects on ability to drive and use machines 
 
Chenodeoxycholic acid has no or negligible influence on the ability to drive and use machines. 
 
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 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 instance of mild intermittent constipation occurred in an adult and another instance 
occurred in a child. One instance 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 instance 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. 
 



6 

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. 
 
4.9 Overdose 
 
The potential for harm from overdose is considered extremely low, as accumulation of 
chenodeoxycholic acid is unlikely due to an efficient endogenous mechanism of elimination and 
excretion.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Alimentary tract and metabolism - Bile therapy - Bile acid preparations, 
ATC code: A05AA01 
 
Mechanism of action 
Exogenous chenodeoxycholic acid is used as replacement therapy to restore the feedback inhibition 
lost due to the deficiency/absence of endogenous chenodeoxycholic acid. In CTX, a defect in the 
CYP27A1 gene results in a deficient mitochondrial sterol 27-hydroxylase enzyme. This deficiency 
blocks the synthesis of primary bile acids via the classical (neutral pathway) and the alternative 
(acidic) pathway. However, cholic acid is still formed via an alternate microsomal pathway. The net 
result is a total bile acid pool that is severely deficient in chenodeoxycholic acid but relatively 
enriched with cholic acid. 
 
In CTX, deficiency of chenodeoxycholic acid causes a lack of feedback of cholesterol 7 alpha 
hydroxylase (CYP7A1) and HMG CoA reductase, causing increased production of atypical bile acids, 
bile alcohols and cholestanol that lead to the pathological consequences of the condition. Exogenous 
replacement with Chenodeoxycholic acid inhibits CYP7A1 (via nuclear receptor, FXR) and HMG 
CoA reductase, thus restoring the feedback inhibition. 
 
The primary pharmacodynamic effects of chenodeoxycholic acid are: 

1. Reduced production of cholesterol: reduces serum cholestanol (action on HMG CoA 
reductase). 

2. Reduced production of cholestanol: reduces serum cholestanol (action on HMG CoA 
reductase and CYP7A1). 

3. Reduced production of atypical bile alcohols and bile acids: through restoration of feedback 
inhibition of primary bile acid synthesis (action on CYP7A1) 

 
Clinical efficacy and safety 
Efficacy and safety was studied in two retrospective trials in two centres in Europe. The mean age of 
the patient population in the pivotal study was younger at 25.8 years than the supporting study 
population at 35 years which also reflected the level of disability present in the two cohorts prior to 
treatment start, with the supporting study having a higher disability score at baseline. 
 
In the pivotal study CDCA-STUK-15-001 treatment of CTX patients with chenodeoxycholic acid 750-
1000 mg/day in adults or 5-15 mg/kg/day in infants and children was associated with statistically 
significant decreases in mean serum levels of cholestanol from baseline to post-baseline in the overall 
population and in the two subgroups of patients aged < 21 years or ≥ 21 years at first treatment. 
Urinary bile level alcohol levels decreased. Neurological disability scale scores (Rankin and EDSS) 
stabilised or improved by the clinical current visit in 84.6% and 76.9% of patients respectively. Mean 
Rankin and EDSS scores showed a very small increase (worsening) from baseline to clinical current 



7 

visit at 0.08 ± 0.74 and 0.27 ± 1.24 in the overall population and this increase was not statistically 
significant. There was a statistically significant (p = 0.04) improvement (decrease) of -0.31 ± 0.48 in 
the mean Rankin score for the < 21 years of age subgroup. 
 
Disease signs and symptoms resolved, improved or stabilised in a majority of patients over the course 
of the study. Diarrhoea disappeared in 100% (23/23 patients) of the patients who had this symptom at 
baseline. There was a resolution, improvement or stabilisation in 88.9% (16/18) of patients with 
cognitive impairment. Epilepsy resolved in 100% (3/3 patients) and polyneuropathy stabilised or 
improved in 100% (11/11). Pyramidal dysfunction improved or stabilised in 60% (10/15) and 
cerebellar dysfunction in 88.7% (12/14). Psychiatric impairment resolved, improved or stabilised in 
85.7% (6/7) of patients. However, parkinsonian symptoms, a rare disease manifestation/association 
that occurred in only 2 patients during the course of the study, did not respond.  
 
In the supportive study CDCA-STRCH-CR-14-001 treatment of CTX patients with chenodeoxycholic 
acid 750 mg/day given for a median duration of 5.75 years was associated with statistically significant 
decreases in mean serum levels of cholestanol from baseline to any post-baseline visit. The mean 
levels of 7α-hydroxy-4-cholesten-3one significantly decreased from baseline to post-baseline Visits 1 
and 2. Vitamin D and PTH levels decreased from baseline to both post-treatment visits and mean 
pyruvate levels decrease from baseline to the first post-treatment visit. Rankin and EDSS scores 
remained stable in 61.5% and 50% of patients respectively, however there was an overall worsening of 
the mean score from baseline. Increases in bone mineral density (Z-score) were observed at lumbar 
spine at both post-treatment visits and at total hip at post-treatment at post-treatment Visit 2. Signs and 
symptoms of the disease remained stable in most of the patients. Diarrhoea improved or disappeared in 
64.3% of the patients who had this symptom present at baseline. 
 
None of the patients had treatment-related adverse events and chenodeoxycholic acid exhibited a 
satisfactory safety profile in relation to routine safety laboratory parameters (haematology and clinical 
chemistry). 
 
5.2 Pharmacokinetic properties 
 
Data exists only in the adult population. 
Chenodeoxycholic acid is an endogenous bile acid in humans, which is tightly regulated by its 
secretion into bile via exporter pumps and detoxification by sulfation. In addition to sulfation, bile acid 
can also be detoxified through glucronidation. 
 
Chenodeoxycholic acid given orally is absorbed in the small intestine. Reabsorption is not complete. A 
small portion of chenodeoxycholic acid is excreted with faeces. 
 
After reabsorption in the intestine, the bile acid is nearly completely conjugated to the amino acids 
glycine and taurine and then excreted again in the bile. 
 
In the intestine Chenodeoxycholic acid and its glycine or taurine conjugate are decomposed by 
bacteria. Deconjugation results in the free bile acid, oxidation in the 7-keto-lithocholic acid and 
lithocholic acid (3α-hydroxycholanic acid) is formed by elimination of the 7-hydroxy group. Whereas 
7-keto-lithocholic acid can be formed partially in the colon and also in the liver to chenodeoxycholic 
acid and ursodeoxycholic acid (3α-, 7ß-di-hydroxycholanic acid), lithocholic acid is absorbed to a 
small extent only and is thus largely lost with faeces. 
 
Biological half-life of chenodeoxycholic acid is about 4 days. 
 
Reabsorption of chenodeoxycholic acid is variable (29 - 84%). After treatment with chenodeoxycholic 
acid, the endogenous synthesis of the primary bile acids, cholic acid and chenodeoxycholic acid, is 
inhibited.  
 
5.3 Preclinical safety data 



8 

 
No formal preclinical safety studies have been conducted however data in the literature reveal no 
special hazard for humans based on conventional studies of single dose toxicity, repeated dose 
toxicity, genotoxicity, and carcinogenic potential. 
 
Rodent and primate toxicity species lack efficient-sulfating capacity for conjugation of lithocholic 
acid, and therefore have shown hepatotoxicity. In contrast, Lithocholic acid sulfate conjugation in 
humans prevents the overt hepatotoxicity, as seen in animal toxicity species after repeat dosing. 
 
Reproduction toxicity 
Developmental toxicity studies in rats, hamsters and primates showed an absence of teratogenic 
effects. In rhesus monkey and baboon studies it was demonstrated that chenodeoxycholic acid dose to 
pregnant animals (at 5-120 mg/kg/day for rhesus monkey; at 18-38 mg/kg/day for baboons) produced 
liver pathology in the developing foetus. Pathological effects on adrenals and kidneys were also seen 
in rhesus monkey foetuses. Maternal effects in the rhesus monkeys, but not baboons, included 
diarrhoea, emesis, weight loss and reduction in food consumption. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
Maize starch  
Magnesium stearate  
Silica, colloidal anhydrous  
Water  
 
Capsule shell 
Gelatine   
Titanium dioxide  
Quinoline yellow  
Erythrosine  
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Capsules are packed in polyvinyl chloride (PVC) blisters sealed with aluminium foil and packed in 
cardboard boxes. 
Packs size: 100 capsules  
 
6.6 Special precautions for disposal and other handling 
 
Patients who are unable to swallow capsules 



9 

For children, adolescents and adults who cannot swallow capsules and/or need to take a dose below 
250 mg, the capsule may be opened, the contents of added to 25 mL of sodium bicarbonate solution 
8.4% (1 mmol/mL) and mixed to produce a suspension containing chenodeoxycholic acid 10 mg/mL. 

For infants the capsules may be opened, the contents added to 50 mL of sodium bicarbonate solution 
8.4% (1 mmol/mL) and mixed to produce a suspension containing chenodeoxycholic acid 5 mg/mL. 

The active substance itself will be dissolved in the sodium bicarbonate solution and it appears as a 
suspension because not all components of the capsule contents will be dissolved. The suspension is 
formed quite easily and is ready when there are no visible lumps or powder left. 

It is recommended that this suspension is prepared at the pharmacy and instructions given to the parent 
on how to administer the suspension. 

The suspension should be stored in a glass bottle. Do not refrigerate or freeze. The suspension is stable 
for up to 7 days. 

The pharmacy should provide oral dose syringes of appropriate volume and grading for administering 
the suspension. The correct volumes should preferably be marked on the oral syringe. 

The doctor should provide information on the dose to be received according to the weight of the child. 
The dose range in children is 5-15 mg/kg per day. 
Further information is provided in the package leaflet under Information for Healthcare Professionals 
Only. 

Any unused product or waste material should be disposed of in accordance with national requirements. 

7. MARKETING AUTHORISATION HOLDER

Leadiant GmbH  
Liebherrstr. 22 
80538 Munich 
Germany 
Telephone: +49 (0)89 5506675 – 0 
Fax: +49  (0) 89 55 066 75 25 
e-mail: info@leadiantbiosciences.com 

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/16/1110/001 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 10/04/2017 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



10 

ANNEX II 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

E. SPECIFIC OBLIGATION TO COMPLETE POST-
AUTHORISATION MEASURES FOR THE MARKETING 
AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 



11 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Pharmaloop S.L. 
C/Bolivia, no 15  
Polígono Industrial Azque 
Alcalá de Henares 
Madrid 28806 
Spain 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-
portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk Management Plan (RMP) 

 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 

 
This being an approval under exceptional circumstances and pursuant to Article 14(8) of 
Regulation (EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the 
following measures: 
 
Description Due date 
In order to collect long term safety and efficacy data in patients treated with Protocol – by 



12 

chenodeoxycholic acid, the MAH will submit the results of a study deriving 
from a registry of patients with inborn errors of primary bile acid synthesis due 
to sterol 27 hydroxylase deficiency in infants, children and adolescents aged 1 
month to 18 years and adults. 

30/11/2017. 
 
Study results – 
PSUR and annual 
reassessments 

 



13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



15 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Chenodeoxycholic acid Leadiant 250 mg hard capsules  
chenodeoxycholic acid 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 250 mg chenodeoxycholic acid. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
100 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 



16 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Leadiant GmbH 
Liebherrstr. 22 
80538 Munich 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1110/001 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Chenodeoxycholic acid Leadiant 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 



17 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER PACKS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Chenodeoxycholic acid Leadiant 250 mg hard capsules  
chenodeoxycholic acid 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Leadiant GmbH 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
LOT 
 
5. OTHER 
 
 
 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



19 

Package leaflet: Information for the user 
 

Chenodeoxycholic acid Leadiant 250 mg hard capsules 
chenodeoxycholic acid 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Chenodeoxycholic acid Leadiant is and what it is used for  
2. What you need to know before you take Chenodeoxycholic acid Leadiant 
3. How to take Chenodeoxycholic acid Leadiant 
4. Possible side effects  
5. How to store Chenodeoxycholic acid Leadiant 
6. Contents of the pack and other information 
 
 
1. What Chenodeoxycholic acid Leadiant is and what it is used for 
 
Chenodeoxycholic acid Leadiant capsules contain a substance called chenodeoxycholic acid. This 
substance is normally produced by the liver from cholesterol. It is a part of the bile, a fluid which helps 
in the digestion of fat and vitamins from food. Patients with a rare condition known as 
cerebrotendinous xanthomatosis (CTX) cannot produce chenodeoxycholic acid and this causes a build-
up of fatty deposits in various areas of the body. This can cause damage to the affected areas. 
 
Chenodeoxycholic acid Leadiant capsules treats CTX by replacing the chenodeoxycholic acid, which 
prevents the build-up of the fatty deposits. 
 
Chenodeoxycholic acid Leadiant capsules can be used from the age of one month and patients with 
CTX will require treatment for the rest of their life. 
 
 
2. What you need to know before you take Chenodeoxycholic acid Leadiant 
 
Do not take Chenodeoxycholic acid Leadiant 
- if you are allergic to chenodeoxycholic acid or any of the other ingredients of this medicine 

(listed in section 6) 
 
Warnings and precautions  
Chenodeoxycholic acid Leadiant should be used under medical supervision. During your treatment, 
your doctor will carry out blood and urine tests to monitor your response to this medicine, and adjust 
your dose if necessary. Your doctor will advise you if for any reason you have to stop treatment with 
Chenodeoxycholic acid Leadiant.  
 
Babies 



20 

The safety and efficacy of Chenodeoxycholic acid Leadiant has not been studied in babies less than 
one month of age. 
 
Other medicines and Chenodeoxycholic acid Leadiant 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
The following medicines may affect the levels of Chenodeoxycholic acid Leadiant: 

• ciclosporin and sirolimus (medicines used to suppress the immune system) 
• phenobarbital (a medicine used for epilepsy) 

If your doctor considers it necessary for you to take ciclosporin, sirolimus or phenobarbital they will 
closely monitor the results of blood and urine tests and adjust the dose of Chenodeoxycholic acid 
Leadiant if necessary. 
 
Oral contraceptives may affect the way in which Chenodeoxycholic acid Leadiant works making it 
less effective. It is not recommended to take oral contraceptives whilst taking Chenodeoxycholic acid 
Leadiant. Please discuss suitable contraceptive methods with your doctor. 
 
The following medicines may reduce the effect of Chenodeoxycholic acid Leadiant: 

• colestyramine, colestipol (so called bile acid sequestrants) 
• medicines to treat heartburn (antacids) containing aluminium hydroxide and/or smectite 

(aluminium oxide)  
If you have to take colestyramine then take Chenodeoxycholic acid Leadiant either one hour before 
colestyramine or 4-6 hours after. 
For the other medicines in this list, take them either 2 hours before or 2 hours after taking 
Chenodeoxycholic acid Leadiant. 
 
Please speak to your doctor if you are taking any of these medicines. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
It is not recommended to take Chenodeoxycholic acid Leadiant during pregnancy and breast-feeding. 
It is not known if Chenodeoxycholic acid Leadiant passes into breast milk. 
 
Women should use an effective contraceptive method whilst taking Chenodeoxycholic acid Leadiant. 
Oral contraceptives are not recommended. Please discuss suitable contraceptive methods with your 
doctor. 
 
Driving and using machines 
Chenodeoxycholic acid Leadiant is not expected to affect your ability to drive or use machines.  
 
 
3. How to take Chenodeoxycholic acid Leadiant 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
The usual starting dose in adults is one 250 mg capsule three times a day. The maximum dose is one 
250 mg capsule four times a day. The capsules should be swallowed whole with water at 
approximately the same time each day. The capsules can be taken with or without food. Your doctor 
may decide to increase your dose depending on how your body responds to treatment. Your doctor 
will tell you how many capsules you need to take, and when you should take the capsules. 
 
Use in children (aged one month to 18 years) 



21 

In babies and children the dose will be calculated from the child’s weight. The starting dose will be 
calculated at 5 mg per kg per day. The maximum dose for children is 15 mg per kg per day. The 
doctor will decide how many times and when your child should receive the dose(s) to make up the 
total dose for the day. Your doctor may change the dose depending on how your child responds to 
treatment. 
 
For babies, children and those who cannot swallow capsules and/or need to take a dose below 250 mg, 
a capsule may be opened and the contents mixed with 8.4% sodium bicarbonate solution. The active 
substance will be dissolved in the sodium bicarbonate solution and as not all the contents of the 
capsule will be dissolved it appears as a mixture. This mixture will be provided to you by your 
pharmacy. Your doctor or pharmacist will give you instructions on how much and how often your 
child needs to take the mixture. 
 
If you take more Chenodeoxycholic acid Leadiant than you should 
Chenodeoxycholic acid Leadiant is unlikely to cause serious side effects. You should contact your 
doctor for advice if you or your child has taken more than the amount prescribed.  
 
If you forget to take Chenodeoxycholic acid Leadiant 
Take your next dose when you would normally take it. Do not take a double dose to make up for a 
forgotten dose.  
 
If you stop taking Chenodeoxycholic acid Leadiant 
This medicine is for long-term use.  Do not stop taking Chenodeoxycholic acid Leadiant without first 
speaking with your doctor. If you stop taking this medicine your symptoms may worsen.   
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects of unknown frequency (cannot be estimated from the available data) 

• Constipation 
• Abnormal liver test values 

 
Reporting of side effects 
If you get any side effects, talk to your doctor or, pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Chenodeoxycholic acid Leadiant 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and blister pack after 
“EXP”. The expiry date refers to the last day of that month. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
- What Chenodeoxycholic acid Leadiant contains 



22 

- The active substance is chenodeoxycholic acid.  
- Each capsule contains 250 mg of chenodeoxycholic acid. 
- The other ingredients are: 

Capsule contents: maize starch, magnesium stearate, silica colloidal anhydrous, water,  
Capsule shell: gelatin, titanium dioxide (E 171), quinoline yellow (E 104), erythrosine (E 127) 

 
What Chenodeoxycholic acid Leadiant looks like and contents of the pack 
Chenodeoxycholic acid Leadiant is provided as hard capsules. The capsules consist of a yellow body 
and an orange cap containing a white compressed powder.  
 
Chenodeoxycholic acid Leadiant is available in blister packs containing 100 hard capsules.  
 
Marketing Authorisation Holder  
Leadiant GmbH 
Liebherrstr. 22 
80538 Munich 
Germany 
e-mail:  info@leadiantbiosciences.com 
 
Manufacturer 
Pharmaloop S.L. 
C/Bolivia, no 15 Polígono Industrial Azque 
Alcalá de Henares 
Madrid 28806 
Spain 
 
This leaflet was last revised in <{MM/YYYY}>. 
 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
 



23 

--------------------------------------------------------------------------------------------------------------------------- 
 
Information for healthcare professionals only 
 
Patients who are unable to swallow capsules 
 
For children, adolescents and adults who cannot swallow capsules and/or need to take a dose below 
250 mg, the capsules may be opened and the contents added to 25 mL of sodium bicarbonate solution 
8.4% (1 mmol/mL) to produce a suspension containing chenodeoxycholic acid 10 mg/mL. 
 
For infants the capsules may be opened and the contents added to 50 mL of sodium bicarbonate 
solution 8.4% (1 mmol/mL) to produce a suspension containing chenodeoxycholic acid 5 mg/mL. 
 
Stir the mixture until all the powder is in suspension. Take care to scrape any powder from the side of 
the bowl into the mixture and stir (for about 5 minutes) to make sure that there are no lumps. The 
mixture is ready when there are no visible lumps or powder. 
 
The suspension produced contains 22.9 mg of sodium per mL, which needs to be taken into 
consideration by patients on a controlled sodium diet. 
 
It is recommended that this suspension is prepared by the pharmacy and instructions given to the 
parent on how to administer the suspension. 
 
The suspension should be stored in a glass bottle. Do not refrigerate or freeze. The suspension is then 
stable for up to 7 days. 
 
The pharmacy should provide oral dose syringes of appropriate volume and grading for administering 
the suspension. The correct volumes should preferably be marked on the oral syringe. 
 
A pharmacy label should be placed on the bottle and include the patient’s name, dosing instructions, 
use by date, name of medicinal product and any other required information to be in compliance with 
local pharmacy regulations. 
 
The doctor should provide information on the dose to be received according to the weight of the child. 
The dose range in children is 5-15 mg/kg per day. 



24 

Dose calculation (Children 1-12yr, adolescents 12-18yr and adults) chenodeoxycholic acid 10 mg/mL 
suspension 
Daily dose: (Weight in kg) x (Dose in mg/kg) = Daily dose in mg 
Divided dose* (Daily dose in mg) = Divided dose in mg 

 (Dose frequency) 
Volume to administer: (Divided dose in mg x 1 ml) = Amount of suspension to give 

              10 mg  
Example: 10 kg patient on a dose of 15 mg/kg of chenodeoxycholic acid. 

 
The total daily dose = 
10 kg x 15 mg/kg = 150 mg 
 
The divided dose when given three times a day = 
150 mg = 50 mg 
     3 
 
The corresponding amount of suspension to give = 
(50 mg x 1 ml) = 5 ml 
      10 mg  
               

*number of divided doses dependant on advice from doctor. 
 
Dose calculation (Infants 1month-1yr) chenodeoxycholic acid 5 mg/mL suspension 
Daily dose: (Weight in kg) x (Dose in mg/kg) = Daily dose in mg 
Divided dose* (Daily dose in mg) = Divided dose in mg 

 (Dose frequency) 
Volume to administer: (Divided dose in mg) x 1 ml = Amount of suspension to give 

                  5 mg  
Example: 3 kg patient on a dose of 5 mg/kg of chenodeoxycholic acid. 

 
The total daily dose = 
3 kg x 5 mg/kg = 15 mg 
 
The divided dose when given three times a day = 
15 mg = 5 mg 
   3 
 
The corresponding amount of suspension to give = 
(5 mg x 1 ml) = 1 ml 
     5 mg  
               

*number of divided doses dependant on advice from doctor. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET