Udarin

White, oval shaped, biconvex, film coated tablets having mid break line one side and plain on other side.
Each film-coated tablet contains: Ursodeoxycholic acid, BP 300 mg.

Bile and liver therapy (bile acids and derivative).
Pharmacology: Pharmacodynamics: Bile acids are among the most important components of the bile and play a role in the stimulation of bile secretion. Bile acids are also important to keep the cholesterol in bile in solution. In a healthy person, the ratio between the concentration of cholesterol and bile acids in the bile is such that the cholesterol will remain in solution for most of the day. In this case, no gallstones can form (the bile is non-lithogenic). In patients with cholesterol stones in the bile, this ratio is changed and the bile is supersaturated with cholesterol (bile is lithogenic). This may cause a precipitation of cholesterol crystals and the formation of gallstones after some time.
The Ursodeoxycholic acid converts lithogenic bile in non-lithogenic bile and gradually dissolves the cholesterol gallstones.
Investigations of the effect of Ursodeoxycholic acid on the cholestasis in patients with impaired biliary drainage and on the clinical symptoms in patients with primary biliary cholangitis and cystic fibrosis have shown that cholestatic symptoms in the blood (to be measured by the increased value of alkaline phosphatase (AF), gamma-GT and bilirubin) and the itch declined rapidly, while also the fatigue decreased in the majority of patients. Moreover, studies seem to indicate a positive benefit-risk ratio of the Ursodeoxycholic acid in children and young adult cystic fibrosis patients with mild to moderate hepatobiliary disorders.
Pediatric population: Cystic fibrosis: From clinical reports long-term experience of 10 years and more has been gained with Ursodeoxycholic acid (UDCA) therapy in pediatric patients suffering from cystic fibrosis associated hepatobiliary disorders (CFAHD). There is evidence that treatment with Ursodeoxycholic acid (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 Ursodeoxycholic acid (UDCA) should be started as soon as the cystic fibrosis associated hepatobiliary disorders (CFAHD) diagnosis is made, in order to optimize the effectiveness of the treatment.
Pharmacokinetics: 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 metabolized. 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 feces.
Resorbed Ursodeoxycholic acid is conjugated again by the liver; 80% of the lithocholic acid formed in the duodenum is excreted in the feces, 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 feces.
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.

Indicated in the treatment of primary biliary cirrhosis (PBC) and for the dissolution of small to medium sized radiolucent, cholesterol-rich gall-stones in patients with a functioning gall bladder.
Cholesterol stones coated with calcium or stones composed of bile pigments are not dissolved by Ursodeoxycholic acid.
Ursodeoxycholic has a particular place in the treatment of patients in whom surgery is contraindicated or who are anxious to avoid surgery.
Pediatric population: Hepatobiliary disorder associated with cystic fibrosis in children aged 6 years to less than 18 years.

Ursodeoxycholic tablets are for oral administration.
To be taken with a drink of water.
Primary Biliary Cirrhosis: Adults and Elderly: 10 - 15 mg Ursodeoxycholic acid (UDCA) per kg per day in two to four divided doses.
Children: Dosage should be related to bodyweight.
Dissolution of gallstones: Adults and Elderly: The usual dose is 6 - 12 mg/kg/day either as a single night time dose or in divided doses. This may be increased to 15 mg/kg/day in obese patients, if necessary.
The duration of treatment may be up to two years, depending on the size of the stone(s), and should be continued for three months after the apparent dissolution of the stone(s).
Children: Dosage should be related to bodyweight.
Pediatric population: Children with cystic fibrosis aged 6 years to less than 18 years: 20 mg/kg/day in 2-3 divided doses, with further increase to 30 mg/kg/day if necessary.

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 feces. No specific counter-measures are necessary and the consequences of diarrhea should be treated symptomatically with restoration of fluid and electrolyte balance.

Ursodeoxycholic acid should not be used in patients: with radio-opaque calcified gall-stones; with acute inflammation of the gall bladder or biliary tract; with occlusion of the biliary tract (occlusion of the common bile duct or a cystic duct); with frequent episodes of biliary colic; with impaired contractability of the gall bladder; with hypersensitivity to bile acids or any excipient of the formulation; who are pregnant or breastfeeding, or in women who may become pregnant; with chronic liver disease, peptic ulcers or in those with inflammatory diseases of the small intestine and colon.

Ursodeoxycholic acid 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 cirrhosis, this monitoring would also enable early detection of potential hepatic deterioration, particularly in patients with advanced stage primary biliary cirrhosis.
When used for the 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 visualized (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 visualized on X-ray images, or in cases of calcified gallstones, impaired contractility of the gall bladder or frequent episodes of biliary colic, Ursodeoxycholic acid should not be used.
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.
If diarrhea occurs, the dose must be reduced and in cases of persistent diarrhea, the therapy should be discontinued. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

There are no adequate data on the use of Ursodeoxycholic acid, particularly in the first trimester of pregnancy. Ursodeoxycholic acid must not be used during pregnancy. Treatment should be discontinued immediately if pregnancy occurs and medical advice sought.
Women of childbearing potential should be treated only if they are using reliable contraception: non-hormonal or low-estrogen oral contraceptive measures are recommended. However, in patients taking Ursodeoxycholic acid 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.
It is not known whether Ursodeoxycholic acid passes into breast milk. Therefore, Ursodeoxycholic acid should not be taken during lactation. If treatment with Ursodeoxycholic acid is necessary, breastfeeding must be discontinued.

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).
Gastrointestinal disorders: In clinical trials, reports of pasty stools or diarrhea during Ursodeoxycholic acid therapy were common.
Very rarely, severe right upper abdominal pain has occurred during the treatment of primary biliary cirrhosis. Ursodeoxycholic acid may give rise to nausea and vomiting. The frequency of these effects are not known.
Hepatobiliary disorders: During treatment with Ursodeoxycholic acid, calcification of gallstones can occur in very rare cases making them unable to be dissolved by bile acid therapy and resulting in surgery for some patients.
During therapy of the advanced stages of primary biliary cirrhosis, in very rare cases decompensation of hepatic cirrhosis has been observed, which partially regressed after the treatment was discontinued.
Skin and subcutaneous disorders: Very rarely, urticaria can occur.
Ursodeoxycholic acid may give rise to pruritus. The frequency of this effect is not known.

Ursodeoxycholic acid should not be administered concomitantly with Charcoal, Cholestyramine, 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.
Ursodeoxycholic acid has been shown to reduce the plasma peak concentrations (Cmax) and the area under the max curve (AUC) of the calcium antagonist nitrendipine. 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.
Oral contraceptives, estrogenic hormones and blood cholesterol lowering agents such as clofibrate may increase biliary lithiasis, which is a counter-effect to Ursodeoxycholic acid used for dissolution of gallstones.

Store at temperatures not exceeding 30°C.
Protect from light.

Cholagogues, Cholelitholytics & Hepatic Protectors

A05AA02 - ursodeoxycholic acid ; Belongs to the class of bile acids. Used in bile therapy.

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