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Manufacturer
TAGI PHARMA
SKU
51224015150

ursodiol 300 mg capsule

Generic
$3.83 / capsule
$7.15 / capsule
$3.32 / capsule
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1,000 capsules Available
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Uses

Gallstone Dissolution

Ursodiol capsules are used for dissolution of gallstones in patients with radiolucent, noncalcified gallbladder stones less than 20 mm in greatest diameter who are not candidates for cholecystectomy because of systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or refusal of surgery; considered pharmacologic treatment of choice in these patients.

Dissolution of gallstones usually requires several months of ursodiol therapy. Complete dissolution of gallstones does not occur in all patients, and recurrence, which may occur within 5 years, is reported in up to 50% of patients who have achieved dissolution of the stones with the drug. Monitor for recurrence of stones.(See Adequate Patient Monitoring under Cautions.)

Successful dissolution of gallstones with ursodiol occurs rarely in patients with calcified gallstones prior to treatment, those who develop stone calcification or gallbladder nonvisualization during treatment, and those with gallstones exceeding 20 mm in greatest diameter.

Successful dissolution is more likely in ursodiol-treated patients with floating or floatable stones (i.e., those with high cholesterol content) and dissolution is inversely related to stone size for stones less than 20 mm in greatest diameter.

Gallbladder nonvisualization prior to treatment is not a contraindication to ursodiol therapy; however, discontinue treatment in patients who develop gallbladder nonvisualization during therapy since this is predictive of failure for complete dissolution.

Prevention of Gallstones

Ursodiol capsules are used for prevention of gallstone formation in obese patients undergoing rapid weight loss.

Ursodiol reduces incidence of gallstone formation in obese patients experiencing rapid weight loss secondary to a very low calorie diet or following gastric bypass surgery.

Primary Biliary Cirrhosis

Ursodiol tablets are used for treatment of primary biliary cirrhosis.

Although optimal treatment for primary biliary cirrhosis remains to be established, many clinicians consider ursodiol the preferred initial treatment.

Substantial improvement in total bilirubin, AST, ALT, alkaline phosphatase, IgM concentrations, and histologic signs of disease has been reported in patients given ursodiol for primary biliary cirrhosis.

In controlled studies, improved biochemical markers (e.g., reduction in serum bilirubin) often were not accompanied by symptomatic improvement or prevention of complications of liver disease (e.g., ascites, GI bleeding). In addition, the impact of favorable changes in bilirubin concentrations on survival and need for liver transplantation has not been elucidated.

Ursodiol reduces the incidence of and delays time to treatment failure (defined as death; need for liver transplantation; histologic progression by 2 stages or to cirrhosis; development of varices, ascites, or encephalopathy; marked worsening of fatigue or pruritus; inability to tolerate the drug; a doubling of or an increase to 1.5 mg/dL or higher of serum bilirubin concentrations; voluntary withdrawal from study or discontinuance of study for any reason).

Ursodiol may delay progression of hepatic fibrosis in patients with early-stage disease; however, in majority of studies no improvement in fibrosis reported.

Ursodiol may delay development of esophageal varices and may improve pruritus.

Dosage and Administration

General

Carefully select patients for ursodiol therapy; consider alternative therapies (e.g., watchful waiting, cholecystectomy).

Administration

Oral Administration

Capsules: Administer orally.

Tablets: Administer orally with food.

Dosage

Adults

Gallstone Dissolution

Oral: Ursodiol 8-10 mg/kg (as capsules) daily in 2-3 divided doses.

Safety of use beyond 24 months of therapy has not been established.

Prevention of Gallstones

Oral: Ursodiol 300 mg (as capsules) twice daily.

Primary Biliary Cirrhosis

Ursodiol 13-15 mg/kg (as tablets) daily in 2-4 divided doses. Adjust dosage regimen according to patient's response and tolerance.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

Select dosage with caution.

Cautions

Contraindications

Hypersensitivity or intolerance to ursodiol, bile acids, or any component of the formulation.

Do not use for dissolution of calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones.

Do not use in patients with compelling reasons for cholecystectomy, including unremitting cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula.

Warnings/Precautions

General Precautions

Hepatic Effects

Institute appropriate specific treatment in patients with primary biliary cirrhosis who have variceal bleeding, hepatic encephalopathy, ascites, or require an urgent liver transplant.

Lithocholic acid, a known hepatotoxin, is formed in the GI tract from ursodiol (to a lesser extent than with chenodiol). Humans are able to sulfate (and thus detoxify) lithocholic acid efficiently; however, it is possible that a rare congenital or acquired deficiency in sulfation could lead to a risk for lithocholate-induced hepatic damage.

Ursodiol has not been associated with liver damage; however, measure AST and ALT at initiation of and during therapy as indicated by particular clinical circumstances.

Adequate Patient Monitoring

Perform ultrasound images of gallbladder at 6-month intervals for first year of therapy to monitor gallstone response.

Most patients who eventually achieve complete stone dissolution will show partial or complete dissolution at first on-treatment evaluation.

If partial stone dissolution is not seen by 12 months of therapy, likelihood of success is greatly reduced.

Continue ursodiol therapy in patients experiencing stone dissolution; reconfirm dissolution by repeat ultrasound within 1-3 months.

Obtain serial ultrasonographic examinations to monitor for recurrence of stones since stone recurrence has been observed in up to 50% of patients within 5 years of complete stone dissolution on ursodiol therapy.

Establish radiolucency of stones before starting another course of ursodiol.

In patients receiving ursodiol tablets for the treatment of primary biliary cirrhosis, monitor liver function tests (γ-glutamyltransferase [GGT, γ-glutamyltranspeptidase, GGTP], AST, ALT) and bilirubin concentrations every month for the first 3 months of therapy and then every 6 months. Rapid decreases in these parameters demonstrate efficacy of treatment. Discontinue ursodiol therapy in patients who experience increases in these parameters.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether ursodiol is distributed into human milk. Use caution.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity and small differences in efficacy cannot be ruled out.

Common Adverse Effects

Capsules (gallstone dissolution): Abdominal pain, diarrhea, viral infection, headache, dyspepsia, upper respiratory tract infection, nausea, sinusitis, constipation, vomiting, pharyngitis, arthralgia, flatulence, back pain, cough, bronchitis, urinary tract infection, arthritis, myalgia, allergy, cholecystitis, rhinitis, fatigue.

Capsules (prevention of gallstone formation): Constipation, diarrhea, headache, nausea, dizziness, vomiting, upper respiratory tract infection, back pain, viral infection, fatigue, influenza-like symptoms, abdominal pain, musculoskeletal pain, dysmenorrhea, alopecia, sinusitis, flatulence.

Tablets (primary biliary cirrhosis): Asthenia, dyspepsia, peripheral edema, hypertension, nausea, GI disorders, chest pain, pruritus.

Drug Interactions

Antacids (Aluminum-containing)

Decreased absorption of ursodiol.

Bile Acid Sequestrants

Decreased absorption of ursodiol. Administer bile acid sequestrants (cholestyramine, colestipol) at least 2 hours before or after ursodiol.

Clofibrate

Possible reduced efficacy of ursodiol because of increased hepatic cholesterol secretion caused by clofibrate (and possibly other antilipemic drugs).

Estrogens

Possible reduced efficacy of ursodiol because of increased hepatic cholesterol secretion caused by estrogens.

Hormonal Contraceptives

Possible reduced efficacy of ursodiol because of increased hepatic cholesterol secretion caused by oral contraceptives.

Pharmacokinetics

Absorption

Bioavailability

Tablets: Absorption from GI tract is incomplete, occurring mainly by passive diffusion.

Capsules: About 90% of an oral dose absorbed in small intestine.

Only small amounts of ursodiol appear in the systemic circulation.

Distribution

Extent

Following absorption from the GI tract, ursodiol distributes to the portal vein and undergoes hepatic extraction (about 50% in the absence of liver disease; extent of extraction decreases as severity of liver disease increases) from portal blood by the liver (i.e., there is a large first-pass effect).

After drug is conjugated in liver, it is distributed into bile.(See Metabolism under Pharmacokinetics.)

Ursodiol in bile is concentrated in the gallbladder and distributed into the duodenum in gallbladder bile via the cystic and common ducts by gallbladder contractions stimulated by physiologic responses to eating.

During chronic administration (13-15 mg/kg daily), ursodiol becomes a major biliary and plasma bile acid, comprising 30-50% of biliary and plasma bile acids. Following discontinuance of the drug, the concentration of ursodiol in bile falls exponentially.

It is not known whether ursodiol is distributed into milk.

Plasma Protein Binding

Healthy individuals: >=70% (as unconjugated ursodiol).

Healthy individuals or patients with primary biliary cirrhosis: extent of protein binding of conjugated ursodiol is not known.

Special Populations

The extent of hepatic extraction of ursodiol from portal blood decreases with increasing severity of liver disease.

Elimination

Metabolism

Ursodiol is conjugated with glycine or taurine in the liver and distributed into bile.

Ursodiol conjugates are absorbed into small intestine by passive and active mechanisms. These conjugates may be deconjugated in the ileum by intestinal enzymes (or by bacteria in the small intestine), creating free ursodiol that can be reabsorbed and reconjugated in the liver.

Unabsorbed ursodiol reaches the colon unchanged, where it is primarily 7-dehydroxylated to form lithocholic acid. Some ursodiol may be epimerized to form chenodiol, which also undergoes 7-dehydroxylation to form lithocholic acid. A small portion of lithocholic acid is reabsorbed and conjugated in the liver with glycine or taurine, and sulfated at the 3 position.

Ursodiol also can be oxidized at the 7-carbon, producing 7-keto-lithocholic acid. Absorbed 7-keto-lithocholic acid is stereospecifically reduced in the liver to chenodiol.

A small portion of orally administered ursodiol undergoes bacterial degradation with each cycle of enterohepatic circulation.

Elimination Route

Ursodiol is excreted principally in the feces. Urinary excretion increases with treatment but remains below 1% except in patients with severe cholestatic liver disease.

Lithocholic acid formed in the small intestine is primarily (80%) excreted in the feces; the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates, which are then excreted into bile and eliminated in the feces.

Half-life

About 4-6 days.

Special Populations

In patients with severe cholestatic liver disease, urinary excretion may increase to over 1% with chronic treatment.

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