Ursotrol

Ursotrol

ursodeoxycholic acid

Manufacturer:

Lloyd

Distributor:

Randril
Full Prescribing Info
Contents
Ursodeoxycholic acid.
Description
Each capsule contains: Ursodeoxycholic acid 250 mg.
Action
Pharmacology: Pharmacokinetics: UDCA occurs naturally in the body. When given orally it is rapidly and completely absorbed. It is 96-98% bound to plasma proteins and efficiently extracted by the liver and excreted in the bile as glycine and taurine conjugates. In the intestine some of the conjugates are deconjugated and reabsorbed. The conjugates may also be dehydroxylated to lithocholic acid, part of which is absorbed, sulphated by the liver and excreted via the biliary tract.
Indications/Uses
Ursodeoxycholic acid capsules are indicated in the treatment of primary biliary cirrhosis (PBC) and for the dissolution of radiolucent gallstones in patients with a functioning gallbladder.
Dosage/Direction for Use
There are no age restrictions on the use of Ursodeoxycholic acid 250 mg hard capsules in the treatment of PBC and for the dissolution of radiolucent gallstones.
The following daily dose is recommended for the various indications: For Primary Biliary Cirrhosis (PBC): The daily dose depends on body weight, and ranges from 3 to 7 capsules (14±2 mg UDCA per kg of body weight).
For the first 3 months of treatment, Ursodeoxycholic acid capsules should be taken divided over the day. With improvement of the liver values the daily dose may be taken once daily in the evening. (See table.)

Click on icon to see table/diagram/image

The capsules should be swallowed whole with some liquid. Care should be taken to ensure that they are taken regularly.
The use of Ursodeoxycholic acid capsules in PBC may be continued indefinitely.
Dissolution of Gallstones: Adults: The usual dose is 8-12 mg/kg/day to be taken in the evening, e.g. 750 mg, daily in the evening.
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 2 mm in diameter. The likelihood of recurrence of gallstones after dissolution by bile acid treatment has been estimated as up to 50% at 5 years. The efficiency of Ursodeoxycholic acid 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% of radiolucent stones and may not be dissolved by bile acids.
Older People: There is no evidence to suggest that any alteration in the adult dose is needed but the relevant precautions should be taken into account.
Paediatric Population: Cholesterol rich gallstones and PBC are very rare in children but when they occur, dosage should be related to bodyweight. There are no adequate data on the efficacy and safety in this population.
Hepatobiliary Disorders Associated with Cystic Fibrosis: Paediatric Population: Children with Cystic Fibrosis Aged 6 to 18 Years: 20 mg/kg/day in 2-3 divided doses, with a further increase to 30 mg/kg/day if necessary.
Overdosage
Diarrhoea may occur in cases of overdose. In general, other symptoms of overdose are unlikely because the absorption of UDCA decreases with increasing dose and therefore more is excreted with the faeces.
No specific counter-measures are necessary and the consequences of diarrhoea should be treated symptomatically with restoration of fluid and electrolyte balance.
Contraindications
Ursodeoxycholic acid 250 mg capsules should not be used in patients with: Acute inflammation of the gall bladder or biliary tract; occlusion of the biliary tract (occlusion of the common bile duct or a cystic duct); frequent episodes of biliary colic; radio-opaque calcified gallstones; impaired contractility of the gall bladder; hypersensitivity to bile acids or any excipient of the formulation.
Special Precautions
Ursodeoxycholic acid 250 mg 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 form allowing for identification of responders and non-responders in patients being treated for PBC, this monitoring would also enable energy 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 250 mg daily and then gradually increased to the recommended dose.
If diarrhoea occurs, the dose must be reduced and in case 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, Ursodeoxycholic acid capsules should not be used.
Female patients taking Ursodeoxycholic acid capsules for dissolution of gallstones should use an effective non-hormonal method of contraception, since hormonal contraceptives may increase biliary lithiasis.
Use In Pregnancy & Lactation
Animal studies did not show an influence of UDCA on fertility. Human data on fertility effects following treatment with UDCA are not available.
Use in 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. UDCA 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 UDCA 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.
Use in Lactation: According to new documented cases of breastfeeding women milk levels of UDCA are very low and probably no adverse reactions are to be expected in breastfed infants.
Adverse Reactions
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.
Drug Interactions
Ursodeoxycholic acid 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 Ursodeoxycholic acid capsules.
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 capsules can reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers 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 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 any may therefore encourage biliary lithiasis, which is a counter-effect to ursodeoxycholic acid used for dissolution of gallstones.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
A05AA02 - ursodeoxycholic acid ; Belongs to the class of bile acids. Used in bile therapy.
Presentation/Packing
Cap 250 mg x 30's.
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