URSOFALK Capsule, hard Ref.[50874] Active ingredients: Ursodeoxycholic acid

Ursofalk capsules should be taken under medical supervision.

During the first 3 months of treatment, liver function parameters AST (SGOT), ALT (SGPT) and γ-GT should be monitored by the physician every 4 weeks, thereafter every 3 months. Apart from allowing for identification of responders and non-responders in patients being treated for PBC, this monitoring would also enable early detection of potential hepatic deterioration, particularly in patients with advanced stage PBC.

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).

Ursofalk capsules should not be administered concomitantly with colestyramine, colestipol or antacids containing aluminium hydroxide and/or smectite (aluminium oxide), because these preparations bind UDCA in the intestine and thereby inhibit its absorption and efficacy. Should the use of a preparation containing one of these substances be necessary, it must be taken at least 2 hours before or after Ursofalk.

Ursofalk capsules can affect the absorption of ciclosporin from the intestine. In patients receiving ciclosporin treatment, blood concentrations of this substance should therefore be checked by the physician and the ciclosporin dose adjusted if necessary.

In isolated cases Ursofalk capsules can reduce the absorption of ciprofloxacin.

In a clinical study in healthy volunteers concomitant use of UDCA (500mg/day) and rosuvastatin (20mg/day) resulted in slightly elevated plasma levels of rosuvastatin. The clinical relevance of this interaction also with regard to other statins is unknown.

UDCA has been shown to reduce the plasma peak concentrations (Cmax) and the area under the curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Close monitoring of the outcome of concurrent use of nitrendipine and UDCA is recommended. An increase of the dose of nitrendipine may be necessary. An interaction with a reduction of the therapeutic effect of dapsone was also reported. These observations together with in vitro findings could indicate a potential for UDCA to induce cytochrome P450 3A enzymes.. Induction has, however, not been observed in a well-designed interaction study with budesonide, which is a known cytochrome P450 3A substrate.

Oestrogenic hormones and blood cholesterol lowering agents such as clofibrate increase hepatic cholesterol secretion and may therefore encourage biliary lithiasis, which is a counter-effect to ursodeoxycholic acid used for dissolution of gallstones.

Animal studies did not show an influence of UDCA on fertility (see section 5.3). Human data on fertility effects following treatment with UDCA are not available.

Pregnancy

There 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.

Breastfeeding

According 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.

UDCA has no or negligible influence on the ability to drive and use machines.

The evaluation of undesirable effects is based on the following frequency data:

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 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 scheme: United Kingdom, Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard

None known.