Ursodiol Information
Ursodiol () Description
Ursodiol () is a bile acid available as 300 mg capsules suitable for oral administration.
Ursodiol () is Ursodiol () USP (ursodeoxycholic acid), a naturally occurring bile acid found in small quantities in normal human bile and in the biles of certain other mammals. It is a bitter-tasting, white powder freely soluble in ethanol and glacial acetic acid; slightly soluble in chloroform; sparingly soluble in ether; and practically insoluble in water. The chemical name for Ursodiol () is 3α, 7β-dihydroxy-5β-cholan-24-oic acid (CHO). Ursodiol () USP has a molecular weight of 392.58. Its structural formula is shown below:
Inactive Ingredients: colloidal silicon dioxide, corn starch, D&C yellow No. 10 aluminum lake, FD&C blue No. 1 aluminum lake, FD&C blue No. 2 aluminum lake, FD&C red No. 40, FD&C red No. 40 aluminum lake, gelatin, magnesium stearate, pharmaceutical glaze (modified) in SD-45, propylene glycol, synthetic black iron oxide, and titanium dioxide. The imprinting ink may contain antifoam DC 1510 and soya lecithin.
Ursodiol () Clinical Pharmacology
About 90% of a therapeutic dose of Ursodiol () is absorbed in the small bowel after oral administration. After absorption, Ursodiol () enters the portal vein and undergoes efficient extraction from portal blood by the liver (i.e., there is a large "first-pass" effect) where it is conjugated with either glycine or taurine and is then secreted into the hepatic bile ducts. Ursodiol () in bile is concentrated in the gallbladder and expelled into the duodenum in gallbladder bile via the cystic and common ducts by gallbladder contractions provoked by physiologic responses to eating. Only small quantities of Ursodiol () appear in the systemic circulation and very small amounts are excreted into urine. The sites of the drug’s therapeutic actions are in the liver, bile, and gut lumen.
Beyond conjugation, Ursodiol () is not altered or catabolized appreciably by the liver or intestinal mucosa. A small proportion of orally administered drug undergoes bacterial degradation with each cycle of enterohepatic circulation. Ursodiol () can be both oxidized and reduced at the 7-carbon, yielding either 7-keto-lithocholic acid or lithocholic acid, respectively. Further, there is some bacterially catalyzed deconjugation of glyco- and tauro- ursodeoxycholic acid in the small bowel. Free Ursodiol () , 7-keto-lithocholic acid, and lithocholic acid are relatively insoluble in aqueous media and larger proportions of these compounds are lost from the distal gut into the feces. Reabsorbed free Ursodiol () is reconjugated by the liver. Eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces. Absorbed 7-keto-lithocholic acid is stereospecifically reduced in the liver to chenodiol.
Lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates. Lithocholic acid is formed by 7-dehydroxylation of the dihydroxy bile acids (Ursodiol () and chenodiol) in the gut lumen. The 7-dehydroxylation reaction appears to be alpha-specific, i.e., chenodiol is more efficiently 7-dehydroxylated than Ursodiol () and, for equimolar doses of Ursodiol () and chenodiol, levels of lithocholic acid appearing in bile are lower with the former. Man has the capacity to sulfate lithocholic acid. Although liver injury has not been associated with Ursodiol () therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated.
Ursodiol () Alternative Therapies
For patients with symptomatic gallstones, surgery offers the advantage of immediate and permanent stone removal, but carries a high risk in some patients. About 5% of cholecystectomized patients have residual symptoms or retained common duct stones. The spectrum of surgical risk varies as a function of age and the presence of disease other than cholelithiasis.
Women in good health or who have only moderate systemic disease and are under 49 years of age have the lowest surgical mortality rate (0.054); men in all categories have a surgical mortality rate twice that of women. Common duct exploration quadruples the rates in all categories. The rates rise with each decade of life and increase tenfold or more in all categories with severe or extreme systemic disease.
Ursodiol () Precautions
Ursodiol () therapy has not been associated with liver damage. Lithocholic acid, a naturally occurring bile acid, is known to be a liver-toxic metabolite. This bile acid is formed in the gut from Ursodiol () less efficiently and in smaller amounts than that seen from chenodiol. Lithocholic acid is detoxified in the liver by sulfation and, although man appears to be an efficient sulfater, it is possible that some patients may have a congenital or acquired deficiency in sulfation, thereby predisposing them to lithocholate-induced liver damage.
Abnormalities in liver enzymes have not been associated with Ursodiol () therapy and, in fact, Ursodiol () has been shown to decrease liver enzyme levels in liver disease. However, patients given Ursodiol () should have SGOT (AST) and SGPT (ALT) measured at the initiation of therapy and thereafter as indicated by the particular clinical circumstances.
Ursodiol () Adverse Reactions
The nature and frequency of adverse experiences were similar across all groups.
The following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level:
Ursodiol () Overdosage
Neither accidental nor intentional overdosing with Ursodiol () has been reported. Doses of Ursodiol () in the range of 16 to 20 mg/kg/day have been tolerated for 6 to 37 months without symptoms by 7 patients. The LD for Ursodiol () in rats is over 5000 mg/kg given over 7 to 10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with Ursodiol () would probably be diarrhea, which should be treated symptomatically.
Ursodiol () Dosage And Administration
The recommended dose for Ursodiol () treatment of radiolucent gallbladder stones is 8 to 10 mg/kg/day given in 2 or 3 divided doses.
Ultrasound images of the gallbladder should be obtained at 6 month intervals for the first year of Ursodiol () therapy to monitor gallstone response. If gallstones appear to have dissolved, Ursodiol () therapy should be continued and dissolution confirmed on a repeat ultrasound examination within 1 to 3 months. Most patients who eventually achieve complete stone dissolution will show partial or complete dissolution at the first on-treatment reevaluation. If partial stone dissolution is not seen by 12 months of Ursodiol () therapy, the likelihood of success is greatly reduced.
Ursodiol () How Supplied
Ursodiol () capsules USP, 300 mg are supplied as hard gelatin capsule with white opaque body and red-orange opaque cap, imprinted “9380” on the body and “TEVA” on the cap in bottles of 100.
Do not store above 86°F (30°C).
Dispense in tight container (USP).
Manufactured In Israel By:
Jerusalem, 91010, Israel
Manufactured For:
Sellersville, PA 18960
Rev. F 1/2011
Ursodiol () Principal Display Panel
New Product Appearance
Ursodiol ()
Capsules USP
300 mg
Rx only
100 CAPSULES
TEVA
