Chenodiol

⛔ FDA Black Box Warning

SPECIAL NOTE Because of the potential hepatoxicity of chenodiol, poor response rate in some subgroups of chenodiol treated patients, and an increased rate of a need for cholecystectomy in other chenodiol treated subgroups, chenodiol is not an appropriate treatment for many patients with gallstones. Chenodiol should be reserved for carefully selected patients and treatment must be accompanied by systematic monitoring for liver function alterations. Aspects of patient selection, response rates and risks versus benefits are given in the insert.

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Available data from published case reports over decades of use with chenodiol during pregnancy have not identified an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Serious hepatic, renal and adrenal lesions occurred in fetuses of female Rhesus monkeys treated at doses 1 to 2 times the recommended human dose based on body surface area (mg/m 2 ). Hepatic lesions also occurred at doses comparable to the human dose based on body surface area in neonatal baboons born to mothers administered chenodiol during pregnancy ( see Data ). The animal study findings have not been demonstrated with human use. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Hepatic lesions were reported in neonatal baboons whose mothers had received 18 to 38 mg/kg of chenodiol throughout pregnancy (0.6 to 1.4 times the recommended human dose based on body surface area). Serious hepatic, renal and adrenal lesions were also reported in fetuses of female Rhesus monkeys given 60 to 90 mg/kg/day from GD 21-45 of pregnancy (1 to 2 times the recommended human dose based on body surface area). Non-human primates form sulfate conjugates of the known hepatotoxic bacterial metabolite of chenodiol, lithocholic acid, to a lesser extent than reported in humans, which may exaggerate the toxicity of orally dosed chenodiol compared to humans. However, there is also evidence that the hepatobiliary toxicity is partly due to the parent drug, chenodiol.