Summary of Product Characteristics Updated 12-Jan-2015 | Dr. Falk Pharma UK Ltd
Paediatric populationHepatobiliary disorders associated with cystic fibrosis in children aged 6 to 18 years
For the treatment of primary biliary cirrhosis (PBC)The daily dose depends on body weight and ranges from 1½ to 3½ tablets (14 ± 2 mg of UDCA per kg of body weight).For the first 3 months of treatment, Ursofalk tablets 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)||Film-coated tablets|
|first 3 months||subsequently|
|morning||midday||evening||evening (1 x daily)|
|47 62||12 16||½||½||½||1½|
|63 78||13 16||½||½||1||2|
|79 93||13 16||½||1||1||2½|
|94 109||14 - 16||1||1||1||3|
For dissolution of cholesterol gallstones:Approximately 10mg of UDCA per kg of body weight, equivalent to:
|up to 60 kg||1 tablet|
|61-80 kg||1½ tablets|
|81-100 kg||2 tablets|
|over 100 kg||2½ tablets|
Paediatric populationBoth indications are very rare in children and adolescents. Therefore there are no adequate data on the efficacy and safety in this population.The administration of Ursofalk is based on body weight and the medical condition.
For the treatment of 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 weight BW (kg)||Daily dose UDCA (mg/kg BW)||Ursofalk 500mg Film-coated Tablets|
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 potentialWomen 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 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.
|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: / Not known (:< 1/10,000 / cannot be estimated from available data)|
Hepatobiliary disorders:During treatment with UDCA, calcification of gallstones can occur in very rare cases. During therapy of the advanced stages of PBC, in very rare cases decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
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 system
United KingdomYellow Card SchemeWebsite: www.mhra.gov.uk/yellowcard
Pharmacotherapeutic group/ATC codeGroup: Bile acid preparationsCode: A05AA02 Small amounts of UDCA are found in human bile. After oral administration, it reduces cholesterol saturation of the bile by inhibiting cholesterol absorption in the intestine and decreasing cholesterol secretion into the bile. Presumably as a result of dispersion of the cholesterol and formation of liquid crystals, a gradual dissolution of cholesterol gallstones occurs. According to current knowledge, the effect of UDCA in hepatic and cholestatic diseases is thought to be due to a relative exchange of lipophilic, detergent-like, toxic bile acids for the hydrophilic, cytoprotective, non-toxic UDCA, to an improvement in the secretory capacity of the hepatocytes, and to immune-regulatory processes.
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 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
Pack sizes:Packs of 50 and 100 film-coated tablets Not all pack sizes may be marketed
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