INTRODUCTION :
Ursodeoxycholic acid and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the colon, primary bile
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UNDESIRABLE EFFECTS :
Ursodil may give rise to nausea, vomiting, diarrhoea and pruritus. A calcified layer may develop on the surface of the stone making it unable to be dissolved by bile acid therapy, resulting in surgery for some patients.
PREGNANCY AND LACTATION :
This product should not be used during pregnancy or lactation. Measures should be taken to prevent pregnancy if given to women of childbearing age. A non-hormonal contraceptive should be used. Treatment should be discontinued immediately if pregnancy occurs and medical advice sought.
CONTRAINDICATIONS :
1. Use in patients with radio-opaque calcified gall-stones, or in those with non-functioning gall bladders.
2. Use in women who may become pregnant.
3. Use in patients with chronic liver disease, peptic ulcers or in those with inflammatory diseases of the small intestine and colon.
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION :
Ursodil tablets should not be administered with oral contraceptives, oestrogenic hormones and other drugs which reduce the blood cholesterol level and increase the bile cholesterol level. Antacids bind bile acids in the gut. Drugs such as charcoal, colestipol and cholestyramine bind bile acids in vitro. All the above should be avoided during bile acid therapy as they may limit the effectiveness of therapy. Ursodeoxycholic acid may increase the absorption and serum levels of ciclosporin in some patients.
Overdose :
Bile acids are removed in the faeces either unchanged or as bacterial metabolites. It is unlikely therefore that serious toxicity would occur following overdose. The most likely result is diarrhoea which should be treated symptomatically and supportively.
How supplied :
Each box contains 1 blister strips of 10 tablets.
CLINICAL TRIALS
Primary Biliary Cirrhosis
Five pivotal randomised, double-blind control studies examined the efficacy of ursodeoxycholic acid in the treatment of primary biliary cirrhosis. All 5 trials were of at least 2 years follow-up. Four of the five studies used a dosage in the range of 10 - 15 mg/kg/day; the fifth trial used a significantly lower dose of 7.7 Ī 0.2 mg/kg/day. Significant improvement in some or all biochemical tests of liver function was shown in subjects given UDCA during the treatment period. Symptom improvement or improvement in histology were not consistently reported with UDCA but longer survival without liver transplantation was reported in two long term studies. One of the studies reported that the efficacy of UDCA in patients with primary biliary cirrhosis was greater in patients with less advanced disease (entry bilirubin < 2mg/dL; histological stage I or II) compared to patients with more advanced disease.
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COMPOSITION :
Ursodeoxycholic acid
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties :
When given by mouth, ursodeoxycholic acid reduces the ratio of cholesterol to bile salts plus phospholipids in bile, causing desaturation of cholesterol saturated bile. The exact mechanism of action has not been fully elucidated.
Pharmacokinetic properties :
Ursodeoxycholic acid is absorbed from the gastro-intestinal tract and undergoes first pass metabolism and enterohepatic recycling. It is partially conjugated in the liver before being excreted into bile and undergoing 7-a dehydroxylation to lithocholic acid, some of which is excreted directly in the faeces. The rest is absorbed and mainly conjugated and sulphated by the liver before excretion in the faeces.
Preclinical safety data :
There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections.
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DOSAGE AND ADMINISTRATION
Adults and the elderly :
10 - 15mg UDCA per kg per day in two to four divided doses are recommended for PBC (primary biliary cirrhosis) and chronic cholestic liver diseases other than CF (cystic fibrosis). This dose can be approximated as follows :
For CF, the general recommended dose is up to 20 mg/kg/day. This dose has been shown to improve histology in PSC patients.
Children:
Data on use in children are very limited. In the few available studies, dosages used have generally been up to 15 - 20 mg/kg/day. In patients with primary biliary cirrhosis, there may, in rare cases, be an initial deterioration in symptoms, e.g. itching. If this is the case, therapy can be continued with 1 capsule daily, and the daily dose gradually increased until the recommended daily dose has been reached. |
