Ursodeoxycholic Acid Tablets
Each sustained-release uncoated tablet contains:
Ursodeoxycholic acid I.P. …………450 mg
Excipients …………………………. q.s.
Dosage form: tablet. Strength: 450mg
Indicated for the dissolution of radiolucent cholesterol gallstones and for the management of chronic cholestatic liver diseases, including primary biliary cirrhosis, primary sclerosing cholangitis, cystic fibrosis–associated cholestasis, and intrahepatic cholestasis of pregnancy.
The dosage should be calculated based on the patient's body weight. The calculated dosage should be rounded to the nearest number of tablets.
Gallstone Dissolution:
Usual dosage: 8 to 10 mg/kg/day, corresponding to, for example, four to six 150 mg tablets, or two to three tablets of 300 mg, or two tablets of 450 mg. The daily dose can be administered two or three times after the meals: two tablets should always be taken after the evening meal. Also a single evening dose can be selected (e.g., a patient of 60 kg, in the evening two tablets of 300 mg). Preferably, this single dose should be taken one hour before bedtime and ± two hours after the evening meal with a glass of milk or a small snack
Gallstone Prevention:
A total daily dose of 600 mg, administered as 300 mg twice daily, is recommended.
Primary Biliary Cholangitis (PBC):
The dosage of ursodeoxycholic acid in primary biliary cholangitis (stages I-III), amounts to 12-15 mg/kg/day, which is equivalent to four to eight tablets of 150 mg, two to four tablets of 300 mg, to be taken in two to three portions during the day, or with two tablets of 450 mg, to be taken in two portions during the day
Children with Cystic Fibrosis (6 to <18 years):
The recommended dose is 20 mg/kg/day administered in 2–3 divided doses, which may be increased up to 30 mg/kg/day if required.
Ursodeoxycholic acid tablets should not be used in patients with:
Paediatric population
Unsuccessful portoenterostomy or without recovery of good bile flow in children with biliary atresia.
Ursodeoxycholic acid tablets should be taken under medical supervision.
During the first three months of the 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 primary biliary cholangitis, this monitoring would also enable an early detection of potential hepatic deterioration, particularly in patients with advanced primary biliary cholangitis.
When used for dissolving 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, the gall bladder, depending on the size of the stones, should be visualized 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 gallbladder cannot be visualized on X-rays, or in cases of calcified gallstones, impaired contractility of the gall bladder or frequent episodes of biliary colic, the treatment with Ursodeoxycholic acid should be discontinued.
When used for the treatment of advanced primary biliary cholangitis:
In very rare cases decompensation of liver cirrhosis is observed which partially decreased after treatment discontinuation.
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.
If diarrhoea occurs, the dosage should be reduced, and treatment should be discontinued in case of persistent diarrhoea.
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
Ursodeoxycholic acid tablets should not be used concurrently with colestyramine, colestipol, or an antacid, on the basis of aluminium hydroxide and/or smectite (aluminium oxide), because these preparations bind ursodeoxycholic acid in the intestine and thereby inhibits its absorption and efficacy. If the use of such a medicine is necessary, must it be taken at least 2 hours before or after Ursodeoxycholic acid.
Ursodeoxycholic acid may affect the absorption of ciclosporin from the intestine. In patients treated with ciclosporin the blood level of ciclosporin should be monitored and the ciclosporin dose should be adjusted, if necessary.
In isolated cases Ursodeoxycholic acid can reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers, the concomitant use of UDCA (500 mg/day) and rosuvastatin (20 mg/day) resulted in slightly elevated plasma levels of rosuvastatin. The clinical relevance of this interaction, also with other statins, is not known. Ursodeoxycholic acid has been shown to reduce the peak plasma concentration (Cmax) and the 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 be an indication that ursodeoxycholic acid can 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.
Oestrogens 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
Pregnancy
There are no or limited amount of data from the use of ursodeoxycholic acid in pregnant women. Studies in animals have shown reproductive toxicity during the early gestation phase
Women of childbearing potential
Women of childbearing potential should be treated with ursodeoxycholic acid, only if they practice reliable contraception: non-hormonal contraceptives or oral contraceptives with low oestrogen dose are recommended. However, in patients taking Ursodeoxycholic acid for dissolving gallstones an 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 ursodeoxycholic acid levels in milk are very low and probably no adverse reactions are to be expected in breastfed infants.
Lactation
Cetirizine, the racemate of levocetirizine, has been shown to be excreted in human milk. Therefore, the excretion of levocetirizine in human milk is likely. Adverse reactions associated with levocetirizine may be observed in breastfed infants. Therefore, caution should be exercised when prescribing levocetirizine to lactating women.
Fertility
Animal studies did not show an influence of ursodeoxycholic acid on fertility. Human data on fertility treatment with ursodeoxycholic acid are not available.
Ursodeoxycholic acid has no or negligible influence on the ability to drive and use machines.
The following adverse reactions have been reported during clinical trials and are ranked using the following frequency: 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 the available data).
Gastrointestinal disorders:
In clinical studies, reports of pasty stools or diarrhoea during treatment with ursodeoxycholic acid were common. In very rare cases, severe right upper abdominal pain has occurred during the treatment of primary biliary cholangitis.
Hepatobiliary disorders:
During treatment with ursodeoxycholic acid calcification of gallstones can occur in very rare cases. During the treatment of advanced stages of primary biliary cholangitis decompensation of cirrhosis has been observed in very rare cases, which partially regressed after treatment discontinuation.
Hypersensitivity reactions:
Very rarely urticaria may occur.
Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorization 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 email to:medico@zorvia.com
By reporting side effects, you can help provide more information on the safety of this medicine.
In the case of overdose diarrhoea may occur. In general, other symptoms of overdose are unlikely, because the absorption of the ursodeoxycholic acid decreases with increasing dose and therefore more is excreted in the faeces.
If diarrhoea occurs, the dosage should be reduced, and treatment should be discontinued in case of persistent diarrhoea.
No specific measures are needed and the consequences of diarrhoea should be treated symptomatically with restoration of fluid and electrolyte balance.
Additional information or special populations
Long-term, high-dose UDCA therapy (28-30 mg/kg/day) by patients with primary sclerosing cholangitis (off-label use) was associated with a higher frequency of serious adverse events.
Ursodeoxycholic acid, a naturally occurring bile acid found in small quantities in normal human bile and in the bile of certain other mammals. It suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol.
About 90% of the therapeutic dose of the ursodeoxycholic acid is rapidly absorbed in the small intestine after oral administration. After the absorption, ursodeoxycholic acid is absorbed in the liver (there is a substantial "first pass-effect"), where it is conjugated with glycine or taurine and then secreted into the bile ducts. Only a small portion of ursodeoxycholic acid is found in the systemic circulation. This is excreted renally. With the exception of conjugation, ursodeoxycholic acid is not metabolised. However, a small fraction of orally administered ursodeoxycholic acid undergoes bacterial conversion to 7-keto- lithocholic acid resp. lithocholic acid after each enterohepatic circulation, while bacterial deconjugation also takes place in the duodenum. Ursodeoxycholic acid, 7- keto-lithocholic acid and lithocholic acid are relatively poorly soluble in water, so a large part of it is excreted via the bile into the faeces. Resorbed ursodeoxycholic acid is conjugated again by the liver; 80% of the lithocholic acid formed in the duodenum is excreted in the faeces, but the remaining 20% of it are sulphated by the liver to insoluble lithocholylconjugates after absorption, which in turn are excreted via the bile and faeces. Resorbed 7-keto-lithocholic acid is reduced to chenodeoxycholic acid in the liver. Lithocholic acid can cause cholestatic liver damage, when the liver is unable to sulphate the lithocholic acid. Although a reduced capacity to sulphate the lithocholic acid in the liver is found in some patients, there is for the time being no clinical evidence that cholestatic liver damage can be associated with the therapy using ursodeoxycholic acid. After repeated dosage, the ursodeoxycholic acid concentration in the bile reaches a "steady state" after approximately 3 weeks: the total concentration of the ursodeoxycholic acid, however, is never higher than about 60% of the total concentration of the bile acid in the bile: also at high doses. After therapy with ursodeoxycholic acid is stopped, the concentration of ursodeoxycholic acid in bile decreases quickly after 1 week to 5-10% of the "steady- state" concentration. The biological half-life of ursodeoxycholic acid is approximately 3.5 to 5.8 days.
Paediatric population - Cystic fibrosis
From clinical reports long-term experience of 10 years and more has been gained with UDCA therapy in paediatric patients suffering from cystic fibrosis associated hepatobiliary disorders (CFAHD). There is evidence that treatment with UDCA can inhibit bile duct proliferation, can halt progression of histological damage and even reverse hepato-biliary changes, if it happens at an early stage of CFAHD. The treatment with UDCA should be started as soon as the CFAHD diagnosis is made, in order to optimize the effectiveness of the treatment.
About 90% of the therapeutic dose of the ursodeoxycholic acid is rapidly absorbed in the small intestine after oral administration. After the absorption, ursodeoxycholic acid is absorbed in the liver (there is a substantial "first pass-effect"), where it is conjugated with glycine or taurine and then secreted into the bile ducts. Only a small portion of ursodeoxycholic acid is found in the systemic circulation. This is excreted renally. With the exception of conjugation, ursodeoxycholic acid is not metabolised. However, a small fraction of orally administered ursodeoxycholic acid undergoes bacterial conversion to 7-keto- lithocholic acid resp. lithocholic acid after each enterohepatic circulation, while bacterial deconjugation also takes place in the duodenum. Ursodeoxycholic acid, 7- keto-lithocholic acid and lithocholic acid are relatively poorly soluble in water, so a large part of it is excreted via the bile into the faeces. Resorbed ursodeoxycholic acid is conjugated again by the liver; 80% of the lithocholic acid formed in the duodenum is excreted in the faeces, but the remaining 20% of it are sulphated by the liver to insoluble lithocholyl conjugates after absorption, which in turn are excreted via the bile and faeces. Resorbed 7-keto-lithocholic acid is reduced to chenodeoxycholic acid in the liver. Lithocholic acid can cause cholestatic liver damage, when the liver is unable to sulphate the lithocholic acid. Although a reduced capacity to sulphate the lithocholic acid in the liver is found in some patients, there is for the time being no clinical evidence that cholestatic liver damage can be associated with the therapy using ursodeoxycholic acid. After repeated dosage, the ursodeoxycholic acid concentration in the bile reaches a "steady state" after approximately 3 weeks: the total concentration of the ursodeoxycholic acid, however, is never higher than about 60% of the total concentration of the bile acid in the bile: also, at high doses. After therapy with ursodeoxycholic acid is stopped, the concentration of ursodeoxycholic acid in bile decreases quickly after 1 week to 5-10% of the "steady- state" concentration. The biological half-life of ursodeoxycholic acid is approximately 3.5 to 5.8 days.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.
Ursodeoxycholic acid is 3α,7β-Dihydroxy-5β-cholan24-oic acid. The empirical formula is C24H40O4 and its molecular weight is 392.6 g/mol. The chemical structural formula is:
structural formula
Not applicable
Refer on pack
Udvia 450 SR is available in pack of 10 tablets.
Store below 30°C. Protect from light.
Ask the patients to inform the treating physicians in case of any of the below:
23rd March 2026