Ursolit

/ CTS

Gallstone dissolution: 8 to 12 mg/kg/day given in 2 divided doses.
If doses are unequal the larger dose should be taken in late evening to counteract the rise in biliary cholesterol saturation which occurs in the early morning. The late evening dose may usefully be taken with food to help maintain bile flow overnight.
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 efficiency of Ursolit 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% radiolucent stones and may not be dissolved by bile acids.
Chronic liver diseases: 10 to 15 mg/kg/day administered in 2 to 4 divided doses with food. The dose may be adjusted according to the patient’s age and severity of symptoms.

Dissolution or reduction in size of radiolucent cholesterol in patient with a functioning gallbladder.
Treatment of chronic liver diseases including primary billiary cirrhosis, primary sclerosing cholangitis, cystic fibrosis associated liver disease, billiary atresia, chronic hepatitis, and alcohol cirrhosis.

– Hypersensitivity to bile acids or any of the excipients.
– Radio-opaque calcified gallstones
– Occlusion of the biliary tract (occlusion of the common bile duct or cystic duct).
– Acute inflammation of the gall bladder or biliary tract.
– Frequent episodes of biliary colic
– Impaired contractility of the gall bladder.
– Active gastric and duodenal ulcers.

This medicinal product should be taken under medical supervision.
During the first 3 months of treatment, the 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 primary biliary cholangitis, this monitoring would also enable an early detection of potential hepatic deterioration, particularly in patients with advanced stage primary biliary cholangitis.
When used for the dissolution of cholesterol gallstones:
In order to be able to assess the therapeutic progression of the dissolution of
gallstones and to timely identify a possible calcification of the stones, depending on stone size, the gall bladder should be visualised 6 to 10 months after the start of the treatment (oral cholecystography) with total image and occlusions and in the standing and lying position (ultrasound investigation).
If the gall bladder cannot be visualised on X-rays, or in cases of calcified gallstones, impaired contractility of the gall bladder or frequent episodes of biliary colic, the
treatment with Ursolit should be discontinued.
When used for treatment of advanced stage of primary biliary cirrhosis:
In very rare cases decompensation of hepatic cirrhosis is observed, which partially decreased after the treatment was discontinued.
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 therapy is to be continued with a dose reduction and subsequently should be gradually increased to the recommended dose as described in the prescribing information.
If diarrhea occurs, the dose should be reduced and in cases of persistent diarrhea, the therapy should be discontinued.
When used for treatment of patients with primary sclerosing cholangitis:
Long-term, high-dose (more than recommended) ursodeoxycholic acid therapy (28-30 mg/kg/day) in patients with primary sclerosing cholangitis was associated with higher rates of serious adverse events.
Female patients who use Ursodeoxycholic acid for dissolving gall stones must use an
effective non-hormonal method of contraception, since hormonal contraception may
increase biliary lithiasis.
Excipient(s):
Lactose
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

Common: Pasty stools, diarrhea.
See prescribing information for full details.

Ursodeoxycholic acid should not be administered concomitantly with colestyramine, colestipol or antacids containing aluminium hydroxide and/or smectite (aluminium oxide), because these preparations bind ursodeoxycholic acid 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 ursodeoxycholic acid.
Ursodeoxycholic acid can increase 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 ursodeoxycholic acid can reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers concomitant use of ursodeoxycholic acid (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.
Ursodeoxycholic acid 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 ursodeoxycholic acid 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 ursodeoxycholic acid to induce cytochrome P450 3A enzymes. Controlled clinical trials have shown, however, that ursodeoxycholic acid does not have a relevant inductive effect on cytochrome P450 3A enzymes.
Oestrogens and blood cholesterol lowering agents such as clofibrate increase hepaticmcholesterol secretion and may therefore encourage biliary lithiasis, which is a counter-effect to ursodeoxycholic acid used for dissolution of gallstones.

Pregnancy:
There are no or limited amounts of data from the use of ursodeoxycholic acid in pregnant women. Studies in animals have shown reproductive toxicity during the early phase of gestation. Ursodeoxycholic acid must not be used during pregnancy unless clearly necessary.
Lactation:
According to few documented cases of breastfeeding women, milk levels of ursodeoxycholic acid are very low and probably no adverse reactions are to be expected in breastfed infants.

Diarrhea may occur in cases of overdose. In general, other symptoms of overdose are unlikely because the absorption of ursodeoxycholic acid decreases with increasing dose and therefore more is excreted with the faeces.
If diarrhoea occurs, the dosage should be reduced, and treatment should be discontinued in case of persistent diarrhoea.
No specific counter-measures are necessary and the consequences of diarrhoea should be treated symptomatically with restoration of fluid and electrolyte balance.