- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Paediatric populationHepatobiliary disorders associated with cystic fibrosis in children aged 6 to 18 years.
For primary biliary cirrhosis (PBC)The daily dose depends on body weight, and ranges from 3 to 7 capsules (14 ± 2 mg UDCA per kg of body weight). For the first 3 months of treatment, Ursofalk capsules should be taken divided over the day. With improvement of the liver values the daily dose may be taken once daily in the evening.
|Body weight (kg)||Daily dose (mg/kg BW)||Ursofalk 250mg hard capsules|
|first 3 months||subsequently|
|morning||midday||evening||evening (1 x daily)|
|47 62||12 16||1||1||1||3|
|63 78||13 16||1||1||2||4|
|79 93||13 16||1||2||2||5|
|94 109||14 16||2||2||2||6|
Dissolution of Gallstones:Adults: The usual dose is 812mg/kg/day to be taken in the evening, e.g. 750mg, daily in the evening.The time required for dissolution of gallstones is likely to range from 6 to 24 months depending on stone size and composition.Follow-up cholecystograms or ultrasound investigation may be useful at 6 month intervals until the gallstones have disappeared.Treatment should be continued until 2 successive cholecystograms and/or ultrasound investigations 4-12 weeks apart have failed to demonstrate gallstones. This is because these techniques do not permit reliable visualisation of stones less than 2mm in diameter. The likelihood of recurrence of gallstones after dissolution by bile acid treatment has been estimated as up to 50% at 5 years. The efficiency of Ursofalk in treating radio-opaque or partially radio-opaque gallstones has not been tested but these are generally thought to be less soluble than radiolucent stones. Non-cholesterol stones account for 10-15% of radiolucent stones and may not be dissolved by bile acids.
Older peopleThere is no evidence to suggest that any alteration in the adult dose is needed but the relevant precautions should be taken into account.
Paediatric populationCholesterol rich gallstones and PBC are very rare in children but when they occur, dosage should be related to bodyweight. There are no adequate data on the efficacy and safety in this population.Hepatobiliary disorders associated with cystic fibrosis:
Paediatric populationChildren with cystic fibrosis aged 6 to 18 years: 20 mg/kg/day in 2-3 divided doses, with a further increase to 30 mg/kg/day if necessary.
|Body weightBW [kg]||Daily dose[mg/kg BW]||Ursofalk 250mg hard capsules|
When used for treatment of advanced stage of primary biliary cirrhosis:In very rare cases decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.In patients with PBC, in rare cases the clinical symptoms may worsen at the beginning of treatment, e.g. the itching may increase. In this case the dose should be reduced to 250mg daily and then gradually increased to the recommended dose described in section 4.2.If diarrhoea occurs, the dose must be reduced and in cases of persistent diarrhoea, the therapy should be discontinued.
When used for dissolution of cholesterol gallstones:In order to assess therapeutic progress and for timely detection of any calcification of the gallstones, depending on stone size, the gall bladder should be visualised (oral cholecystography) with overview and occlusion views in standing and supine positions (ultrasound control) 6-10 months after the beginning of treatment.If the gall bladder cannot be visualised on X-ray images, or in cases of calcified gallstones, impaired contractility of the gall bladder or frequent episodes of biliary colic, Ursofalk should not be used. Female patients taking Ursofalk for dissolution of gallstones should use an effective non-hormonal method of contraception, since hormonal contraceptives may increase biliary lithiasis (see section 4.5. and 4.6.)
PregnancyThere are no or limited amounts of data from the use of UDCA in pregnant women. Studies in animals have shown reproductive toxicity during the early phase of gestation (see section 5.3). Ursofalk must not be used during pregnancy unless clearly necessary.
Women of childbearing potential:Women of childbearing potential should be treated only if they use reliable contraception: non-hormonal or low-oestrogen oral contraceptive measures are recommended. However, in patients taking Ursofalk capsules for dissolution of gallstones, effective non-hormonal contraception should be used, since hormonal oral contraceptives may increase biliary lithiasis.The possibility of a pregnancy must be excluded before beginning treatment.
BreastfeedingAccording to few documented cases of breastfeeding women, milk levels of UDCA are very low and probably no adverse reactions are to be expected in breastfed infants.
Gastrointestinal disorders:In clinical trials, reports of pasty stools or diarrhoea during UDCA therapy were common. Very rarely, severe right upper abdominal pain has occurred during the treatment of PBC.
Skin and subcutaneous tissue disorders:Very rarely, urticaria can occur.
Reporting of suspected adverse reactionsReporting 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 scheme:
United KingdomYellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard
Additional information on special populations:Long-term, high-dose UDCA therapy (28-30 mg/kg/day) in patients with primary sclerosing cholangitis (off-label use) was associated with higher rates of serious adverse events.
Cystic fibrosis - Paediatric populationFrom clinical reports long-term experience up to 10 years and more is available with UDCA treatment in paediatric patients suffering from cystic fibrosis associated hepatobiliary disorders (CFAHD). There is evidence that treatment with UDCA can decrease bile duct proliferation, halt progression of histological damage and even reverse hepatobiliary changes if given at early stage of CFAHD. Treatment with UDCA should be started as soon as the diagnosis of CFAHD is made in order to optimise treatment effectiveness.
a) Acute toxicityAcute toxicity studies in animals have not revealed any toxic damage.
b) Chronic toxicitySubchronic toxicity studies in monkeys showed hepatotoxic effects in the groups given high doses, including functional changes (e.g. liver enzyme changes) and morphological changes such as bile duct proliferation, portal inflammatory foci and hepatocellular necrosis. These toxic effects are most likely attributable to lithocholic acid, a metabolite of UDCA, which in monkeys unlike humans is not detoxified. Clinical experience confirms that the described hepatotoxic effects are of no apparent relevance in humans.
c) Carcinogenic and mutagenic potentialLong-term studies in mice and rats revealed no evidence of UDCA having carcinogenic potential. In vitro and in vivo genetic toxicology tests with UDCA were negative.The tests with UDCA revealed no relevant evidence of a mutagenic effect.
d) Toxicity to reproductionIn studies in rats, tail malformations occurred after a dose of 2000 mg of ursodeoxycholic acid per kg of body weight. In rabbits, no teratogenic effects were found, although there were embryotoxic effects (from a dose of 100 mg per kg of body weight). UDCA had no effect on fertility in rats and did not affect peri-/post-natal development of the offspring.
Dr. Falk Pharma UK Ltd
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