Chenodal

Bile Acid Agents

Administer orally with or without food.

new primary malignancy / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known

diarrhea / Early / 30.0-40.0
dyspepsia / Early / Incidence not known
flatulence / Early / Incidence not known
pyrosis (heartburn) / Early / Incidence not known
nausea / Early / Incidence not known
fecal urgency / Early / Incidence not known
anorexia / Delayed / Incidence not known
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known

Chenodal

Rx

Oral formulation of naturally occurring human bile acid; indicated for dissolution of radiolucent gallstones in select patients when surgery is not possible; most effective on small or floatable stones; therapy reserved for carefully selected patients due to treatment-related hepatotoxicity.

Initially, 250 mg PO twice daily for 2 weeks, then increase the dose by 250 mg/day each week until the recommended or maximum tolerated dose is achieved. The recommended dosage range is 13 to 16 mg/kg/day PO given in 2 divided doses. Dosages less than 10 mg/kg/day are not recommend as they are usually ineffective and may increase the risk of cholecystectomy. If diarrhea occurs, temporarily decrease dose; once symptoms resolve, attempt to reinstate the previous dose. Discontinue treatment if there is no response by 18 months; safe use beyond 24 months has not been established.

Chenodiol is contraindicated in the presence of known hepatocyte dysfunction. Safe use of chenodiol depends upon selection of patients without pre-existing hepatic disease and upon careful monitoring of serum aminotransferase concentrations to detect drug-induced liver toxicity.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Aluminum Hydroxide: (Moderate) Aluminum hydroxide based antacids have been shown to adsorb bile acids in vitro and are expected to interfere with the efficacy of chenodiol. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 2 hours after the aluminum-based antacid.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Aluminum hydroxide based antacids have been shown to adsorb bile acids in vitro and are expected to interfere with the efficacy of chenodiol. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 2 hours after the aluminum-based antacid.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Aluminum hydroxide based antacids have been shown to adsorb bile acids in vitro and are expected to interfere with the efficacy of chenodiol. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 2 hours after the aluminum-based antacid.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Aluminum hydroxide based antacids have been shown to adsorb bile acids in vitro and are expected to interfere with the efficacy of chenodiol. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 2 hours after the aluminum-based antacid.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Aluminum hydroxide based antacids have been shown to adsorb bile acids in vitro and are expected to interfere with the efficacy of chenodiol. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 2 hours after the aluminum-based antacid.
Charcoal: (Major) Activated charcoal, which is available in some dietary supplements, has been shown to adsorb bile acids in vitro and is expected to interfere with the efficacy of chenodiol. Concurrent use is not recommended.
Cholestyramine: (Moderate) Bile acid sequestrants, such as cholestyramine, may interfere with the action of chenodiol by reducing its absorption. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 4 hours after cholestyramine.
Colesevelam: (Moderate) Bile acid sequestrants, such as colesevelam, may interfere with the action of chenodiol by reducing its absorption. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 4 hours after colesevelam.
Colestipol: (Major) Bile acid sequestrants, such as colestipol, may interfere with the action of chenodiol by reducing its absorption. To minimize drug interactions, administer chenodiol at least 1 hour before or at least 4 hours after colestipol.
Conjugated Estrogens: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Dienogest; Estradiol valerate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Diethylstilbestrol, DES: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Drospirenone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Drospirenone; Estetrol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Drospirenone; Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Esterified Estrogens: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estradiol; Levonorgestrel: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estradiol; Norethindrone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estradiol; Norgestimate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estradiol; Progesterone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estrogens: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Estropipate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Fibric acid derivatives: (Major) Fibric acid derivatives (i.e., clofibrate and perhaps other lipid-lowering fibrate drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of chenodiol.
Leuprolide; Norethindrone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Levonorgestrel: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norethindrone: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Norgestrel: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens and combination hormonal oral contraceptives increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may theoretically counteract the effectiveness of chenodiol.
Warfarin: (Moderate) Due to its potential for hepatotoxicity, chenodiol may affect the pharmacodynamics of warfarin. Patients with hepatic impairment may require a lower dosage of warfarin due to decreased warfarin metabolism and decreased production of coagulation factors. Coadministration with chenodiol can cause prolongation of the prothrombin time and increase the risk of bleeding. Monitor patients on concomitant therapy carefully. If prolongation of prothrombin time is observed, the warfarin dosage should be adjusted as needed to produce a prothrombin time 1.5 to 2 times normal. If necessary, discontinue chenodiol therapy.

Chenodal Oral Tab: 250mg

Maximum dosage information is not available.

Maximum dosage information is not available.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

The sites of action of chenodiol are the liver, bile, and the colon. At therapeutic doses, chenodiol suppresses the hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones. Chenodiol has no effect on radiopaque (calcified) gallstones or on radiolucent bile pigment stones. The large majority of the chenodiol in the body is found in the enterohepatic circulation; serum and urinary bile acid concentrations are not significantly affected during chenodiol therapy.
 
Although chenodiol therapy has been linked to hepatotoxicity, the mechanism by which this occurs is unclear. Lithocholic acid, a major metabolite of chenodiol and an established hepatotoxin, may be the cause of chenodiol-related hepatotoxicity; however, since humans possess an efficient mechanism for sulfating and eliminating this substance, there is some evidence that the demonstrated hepatotoxicity could be due, at least in part, to chenodiol itself. Moreover, the possible variations that may exist between individual patient's capacity to sulfate and eliminate lithocholic acid has not been clearly established. Published literature suggests that patients who develop chenodiol-induced serum aminotransferase elevations may be poor sulfators of lithocholic acid.

Chenodiol is administered orally.
 
During chenodiol therapy, serum and urinary bile acid concentrations are not significantly affected. Once steady-state is achieved, an amount of chenodiol that approximates the daily dose escapes to the colon. In the colon, chenodiol is converted by bacterial action to lithocholic acid, a major metabolite of chenodiol. Approximately 80% of the lithocholate is excreted in the feces with the remainder being absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. Fecal bile acids are increased 3- to 4-fold, while biliary lithocholate is only increased slightly.

After oral administration, chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. Between 60% and 80% of chenodiol undergoes first-pass hepatic clearance; therefore, the body pool of chenodiol resides mainly in the enterohepatic circulation.

Chenodiol is classified in FDA pregnancy risk category X. Chenodiol may cause fetal harm when administered to a pregnant woman; however, no human data are available at this time. In sub-human primate studies, serious hepatic, renal, and adrenal lesions have occurred. Chenodiol is therefore contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazards to the developing fetus.

According to the manufacturer, because many drugs are excreted into breast milk, caution should be used when chenodiol is administered to a breast-feeding mother. It is not known whether chenodiol is excreted in human milk. Possible effects on a nursing infant are not defined. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.