Reltone Drug Information

1. Reltone™ is indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Safety of use of Reltone™ beyond 24 months is not established. 2.

Reltone™ is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.

Gallstone Dissolution The recommended dose for Reltone™ treatment of radiolucent gallbladder stones is 8-10 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 Reltone™ therapy to monitor gallstone response. If gallstones appear to have dissolved, Reltone™ 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 Reltone™ therapy, the likelihood of success is greatly reduced. Gallstone Prevention The recommended dosage of Reltone™ for gallstone prevention in patients undergoing rapid weight loss is 600 mg/day.

To report SUSPECTED ADVERSE REACTIONS, contact Intra-Sana Laboratories at 1-702-980-8963 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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:

Drug Interactions Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of ursodiol by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with ursodiol in the same manner as the bile acid sequestering agents. Estrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) increase hepatic cholesterol secretion and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodiol.

Pregnancy Reproduction studies have been performed in rats and rabbits with ursodiol doses up to 200-fold the therapeutic dose and have revealed no evidence of impaired fertility or harm to the fetus at doses of 20- to 100-fold the human dose in rats and at 5-fold the human dose (highest dose tested) in rabbits. Studies employing 100- to 200-fold the human dose in rats have shown some reduction in fertility rate and litter size. There have been no adequate and well-controlled studies of the use of ursodiol in pregnant women, but inadvertent exposure of 4 women to therapeutic doses of the drug in the first trimester of pregnancy during the ursodiol trials led to no evidence of effects on the fetus or newborn baby.

Although it seems unlikely, the possibility that ursodiol can cause fetal harm cannot be ruled out; hence, the drug is not recommended for use during pregnancy.

Pediatric Use The safety and effectiveness of ursodiol in pediatric patients have not been established.

1. Reltone™ will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones. Hence, patients with such stones are not candidates for Reltone™ therapy. 2.

Patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for Reltone™ therapy. 3. Allergy to bile acids.

Neither accidental nor intentional overdosing with ursodiol has been reported. The most likely manifestation of severe overdose with ursodiol would probably be diarrhea, which should be treated symptomatically.