Destolit 150 mg tablets

Each tablet contains 150 mg ursodeoxycholic acid (UDCA)

Tablet

The dissolution of radiolucent (i.e. non-radio opaque) cholesterol gallstones in patients with a functioning gallbladder

Adults and the elderly

Dissolution of gallstones:

A daily dose of 8 to 12mg/kg UDCA will produce cholesterol desaturation in the majority of cases. The measurement of the lithogenic index on bile-rich duodenal drainage fluid after 4-6 weeks of therapy may be useful for determining the minimum effective dose. The lowest effective dose has been found to be 4 mg/kg. The daily dose for most patients is 3 or 4 tablets, according to body weight. The dose should be divided into two administrations after meals, with one administration always after the evening meal.

The duration of treatment needed to achieve dissolution will not usually exceed 2 years, and should be monitored with regular cholecystograms. Treatment should be continued for 3-4 months after the radiological disappearance of gallstones.

Any temporary discontinuation of treatment, if prolonged for 3-4 weeks, will allow the bile to return to a state of supersaturation, and will extend the total time taken for litholysis. In some cases stones may recur after successful treatment.

Children and adolescents

Not recommended.

For oral administration.

Active gastric or duodenal ulcers, a non-functioning gall bladder, radio-opaque gall stones and inflammatory bowel disease are contraindicated, as are hepatic and intestinal conditions interfering with the enterohepatic circulation of bile acids (ileal resection and stoma, regional ileitis, extra and intra-hepatic cholestasis, severe, acute, and chronic liver diseases).

Excessive dietary intake of calories and cholesterol should be avoided; a low cholesterol diet will probably improve the effectiveness of Destolit tablets.

Drugs such as cholestyramine and some antacids bind bile acids in vitro, and may inhibit the absorption of UDCA.

There is a possibility of increased serum ciclosporin levels in some patients taking ursodeoxycholic acid and ciclosporin simultaneously.

It is recommended that drugs known to increase cholesterol elimination in bile, such as oestrogenic hormones, oral contraceptive agents and certain blood cholesterol lowering agents, such as clofibrate, should also not be prescribed concomitantly.

It is advised that women of child bearing age should use adequate nonhormonal or low oestrogen oral contraceptive measures during treatment with UDCA, and that the drug should not be given during the first trimester of pregnancy unless, in the opinion of the physician, the benefit outweighs the risk.

There are no clinical data available on the safety of UDCA in women who are breast-feeding. Therefore, Destolit is not recommended in this patient group.

None known

Destolit is normally well tolerated. Diarrhoea has been found to occur only occasionally. No significant alterations have so far been observed in liver function. Nausea, vomiting, pruritus and gallstone calcification may occur.

It is unlikely that overdosage will cause serious adverse effects. Diarrhoea may occur and it is recommended that liver function tests be monitored. Ion-exchange resins may be useful to bind bile acids in the intestine.

Ursodeoxycholic acid is a gallstone dissolving agent which acts by reducing the content of cholesterol in bile. This may be due either to a reduction in hepatic cholesterol synthesis or reduced absorption of cholesterol or both.

Intestinal absorption after an oral dose of UDCA is high, with a first-pass clearance of about 50 to 60%. Studies show that passive diffusion occurs, whereupon the drug enters the enterohepatic circulation and is subject to an efficient hepatic extraction mechanism. The 'spillover' into the systemic blood supply is therefore minimal. Plasma levels are not clinically important but may be useful in estimating patient compliance; they reach maximum concentrations at about 60 minutes after ingestion with another peak recorded at 3 hours.

Ursodeoxycholic acid is rapidly conjugated with glycine and taurine in the liver. Microbial biotransformation of the drug and its metabolites occurs when they leave the enterohepatic circulation and is responsible for high levels of faecal lithocholic and 7-ketolithocholic acids during ursodeoxycholic acid therapy. Intestinal flora also hydrolyse conjugated drug back to the parent compound and interconvert ursodeoxycholic and chenodeoxycholic acids.

UDCA has not shown teratogenic potential in rats and rabbits; embryotoxicity seen in the rat at high doses appears to occur early in gestation.

UDCA was not genotoxic in bacterial mutation tests. It has shown genotoxic potential in vitro in a mammalian chromosome aberration study and in a gene mutation study using yeast, however, the relevance of this is questionable since UDCA was not carcinogenic in long term studies in mice and rats.

Bile acids act as tumour promoters in colon carcinogenesis, but there is no evidence that they are direct carcinogens. In two year carcinogenicity studies UDCA was not tumourigenic in mice. In rats an increase in adrenal phaeochromocytomas was observed which is not considered to be clinically significant

Lactose, pregelatinised maize starch, acacia gum, talc, magnesium stearate, purified water.

None known

3 years

None

Blister pack of 60 tablets

None

Norgine Ltd

Chaplin House

Widewater Place

Moorhall Road

Harefield

Uxbridge

Middlesex

UB9 5NS

PL 00322/0076

22 August 2002

January 2009

Legal category POM