URSOGRIX Capsule, hard Ref.[49916] Active ingredients: Ursodeoxycholic acid

Ursodeoxycholic acid should be used under medical supervision.

During the first 3 months of treatment, liver function parameters AST (SGOT), ALT (SGPT), ALP and γ‑GT should be monitored by the physician every 4 weeks, and every 3 months thereafter. As well as allowing for differentiation between responsive and non-responsive patients treated for PBC, this monitoring also enables early detection of potential deterioration in liver function, especially in patients with advanced PBC.

When used for dissolution of gallstones

In order to assess the therapeutic progression of gallstone dissolution and to promptly detect any calcification of the gallstones, the gallbladder should be visualised (oral cholecystography) 6-10 months after the start of treatment, depending on stone size, with overview and occlusions in standing and supine positions (ultrasound control).

If the gallbladder cannot be visualised on X-ray images, or in cases of calcified gallstones, impaired contractility of the gallbladder or frequent episodes of biliary colic, treatment with this medicinal product must be discontinued.

Female patients taking this medicinal product to dissolve gallstones should use an effective non-hormonal contraceptive, as hormonal contraceptives may promote the formation of gallstones (see sections 4.5 and 4.6).

When used to treat patients with advanced PBC

In very rare cases decompensation of liver cirrhosis has been observed, which partially regressed upon discontinuation of treatment.

In patients with PBC, the clinical symptoms may worsen in rare cases at the start of treatment, e.g. pruritus may increase. In this case, the dosage of this medicinal product can be reduced to one 250 mg capsule per day and subsequently should be gradually increased to the recommended dose as described in section 4.2.

If diarrhoea occurs, the dosage must be reduced and, in the event of persistent diarrhoea, treatment must be discontinued.

This medicine should not be used concomitantly with colestyramine, colestipol or antacids containing aluminium hydroxide and/or smectite (aluminium oxide), as these substances can bind Ursogrix in the intestine, thereby reducing absorption and efficacy. If the use of any such medicine is needed, it must be taken at least 2 hours before or after Ursogrix.

This medicinal product can affect the absorption of ciclosporin from the intestine. In patients treated with ciclosporin, blood levels of the latter must therefore be monitored by the physician and the ciclosporin dosage adjusted if necessary. Due to the effect of ursodeoxycholic acid on the secretion of bile acids there is a theoretical possibility that the absorption of other lipophilic substances could be affected.

In isolated cases, Ursogrix 250 mg hard capsules can reduce the absorption of ciprofloxacin.

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

This medicinal product reduces the peak plasma concentration (C_max) and the area under the curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Close monitoring of the outcome of concomitant use of nitrendipine and Ursogrix is recommended. It may be necessary to increase the dosage of nitrendipine. An interaction with dapsone has also been reported, with a reduction in its therapeutic effect. These observations, together with in vitro data, might indicate that Ursogrix can induce cytochrome P450 3A enzymes. However, induction has not been observed in a well-designed interaction study with budesonide, a known cytochrome P450 3A substrate.

Oestrogens and blood cholesterol-lowering agents, such as clofibrate, increase hepatic cholesterol secretion and may thereby stimulate formation of gallstones; this effect is counteractive in the use of this medicinal product for gallstone dissolution.

Pregnancy

There are no or limited of data from the use of Ursogrix in pregnant women. Studies in animals have shown reproductive toxicity during the early phase of gestation (see section 5.3). Therefore, this medicinal product should not be used during pregnancy unless clearly necessary.

Women of childbearing potential

Women of childbearing potential may only be treated with Ursogrix if they use reliable contraception: non‑hormonal contraception or oral contraception with a low oestrogen dosage is recommended. However, in patients using this medicinal product to dissolve gallstones, effective non-hormonal contraception should be used, as hormonal oral contraceptives can increase formation of gallstones (see section 4.4). The possibility of a pregnancy must be excluded before beginning of the treatment.

Breast-feeding

According to a few documented cases of breastfeeding women, the amount of Ursogrix in milk was very low and no adverse reactions are to be expected in breastfed infants.

Fertility

Animal studies did not indicate any effect of this medicinal product on fertility (see section 5.3). Human data on fertility effects after treatment with this medicinal product are not available.

Ursogrix 250 mg hard capsules has no or negligible influence on the ability to drive and use machines.

The evaluation of undesirable effects is based on the following frequencies: 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 available data).

Gastrointestinal disorders

Common: pasty stools or diarrhoea.

Very rare: severe right upper abdominal pain has occurred during treatment of PBC.

Hepatobiliary disorders

Very rare: calcification of gallstones; decompensation of liver cirrhosis (during the treatment of advanced stages of PBC), which partially regressed upon discontinuation of treatment.

Skin and subcutaneous tissue disorders

Very rarely: urticaria.

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 HPRA Pharmacovigilance, Website: www.hpra.ie.

Not applicable.