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This monograph summarizes the toxicological and lactation safety profile of bile acid preparations classified under ATC A05AA, with a focus on chenodeoxycholic acid and ursodeoxycholic acid as used in contemporary clinical practice.medpedia.framar+1

ATC group overview

ATC A05AA belongs to the broader A05 “Bile and liver therapy” subgroup within the “Alimentary tract and metabolism” anatomical main group, and includes bile acids and their derivatives used primarily in bile therapy.wikipedia
In Bulgarian pharmaco-therapeutic practice, A05AA currently covers chenodeoxycholic acid (A05AA01) and ursodeoxycholic acid (A05AA02), which are the main bile acids used to treat gallstone disease and cholestatic disorders.bionity+1

Pharmacological class and mechanism

Bile acids are steroid acids synthesized in hepatocytes, secreted into bile canaliculi and drained via the biliary tree to the duodenum, where they play a key role in digestion and absorption of dietary fats.medpedia.framar
Chenodeoxycholic and ursodeoxycholic acids modify the bile acid pool and biliary cholesterol saturation; they can dissolve radiolucent cholesterol gallstones and exert cytoprotective and choleretic effects in cholestatic liver disease.kegg+1

Clinical indications

Within ATC A05AA, bile acid preparations are used for oral dissolution of cholesterol gallstones that are radiolucent and located in a functioning gallbladder, for biliary reflux gastritis, and for chronic cholestatic liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis.droracle+1
Ursodeoxycholic acid in particular is standard therapy for several cholestatic disorders and for intrahepatic cholestasis of pregnancy, while chenodeoxycholic acid has more restricted indications due to safety concerns.europa+1

Chenodeoxycholic acid (A05AA01) – toxicology

Chenodeoxycholic acid (CDCA) is a primary bile acid that reduces biliary cholesterol saturation and can dissolve cholesterol gallstones, but its therapeutic use is limited by dose-related hepatotoxicity and hypercholesterolemia.medbox.iiab+1
Product information for CDCA emphasizes that a risk to newborns and infants cannot be excluded, and that if treatment is necessary in a breastfeeding woman, a decision must be made between discontinuing breastfeeding or discontinuing/abstaining from chenodeoxycholic acid therapy.europa

Chenodeoxycholic acid – lactation safety

Specialized lactation safety resources classify chenodeoxycholic acid as “compatible” with breastfeeding but with “low risk” and advise follow‑up, reflecting limited available data and potential theoretical risks.e-lactation
Given conflicting information between regulatory documents (caution; risk cannot be excluded) and lactation safety databases (low risk), chenodeoxycholic acid should be considered a second‑line or avoidable agent in lactating women, especially when a safer alternative such as ursodeoxycholic acid is available.e-lactation+1

Ursodeoxycholic acid (A05AA02) – toxicology

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with a favorable safety profile in adults, commonly used as long‑term therapy in primary biliary cholangitis and other cholestatic liver diseases.e-lactation+1
UDCA is associated with relatively few adverse effects; typical reactions include mild gastrointestinal symptoms, pruritus or rash, and rarely more serious hepatobiliary complications, while it has also been used therapeutically in newborns and older infants, supporting a benign toxicological profile.droracle+1

Ursodeoxycholic acid – lactation safety

UDCA is excreted into breast milk only in negligible amounts; total bile acid concentrations in breast milk of UDCA‑treated mothers are identical to untreated controls, and measured UDCA levels around 0.69 µmol/L do not contribute to the newborn bile acid pool.publications.cuni+1
Clinical follow‑up of infants exposed via breast milk for one year shows no apparent adverse effects or developmental problems, and contemporary expert publications conclude that therapeutic administration of UDCA during lactation is safe and should be explicitly allowed in guidelines for cholestatic disease therapy in breastfeeding mothers.publications.cuni+1

Guideline and regulatory perspectives for UDCA

Recent hepatology guidelines from European liver societies strongly recommend continuing UDCA therapy during breastfeeding in women with cholestatic liver diseases, stating that breastfeeding should not be discouraged when UDCA is indicated.droracle
Older regulatory texts and some drug labels remain conservative, stating that it is not known whether UDCA is excreted in human milk and advising caution or weaning, but these positions predate and are not supported by newer pharmacokinetic and clinical safety data.midlandsmedicines+1

Comparative toxicological‑lactological assessment within A05AA

Within the A05AA class, ursodeoxycholic acid has the best characterized and most favorable lactation safety profile, with robust data showing negligible milk transfer and absence of infant harm, leading lactation databases to classify it as “very low risk” and compatible with breastfeeding.publications.cuni+2
Chenodeoxycholic acid, by contrast, is supported mainly by limited lactation data and more cautious regulatory language, so in breastfeeding women UDCA should be preferred whenever a bile acid preparation is clinically indicated, and CDCA reserved for situations where benefits clearly outweigh potential risks and breastfeeding can be managed accordingly.e-lactation+1

Practical prescribing considerations in lactation

For full‑term, healthy breastfed infants, UDCA at standard therapeutic doses for cholestatic liver disease (commonly in the range of 15–20 mg/kg/day in adults) is considered compatible with breastfeeding, without need for additional infant monitoring beyond routine pediatric care.publications.cuni+1
In contrast, chenodeoxycholic acid should generally be avoided during breastfeeding if a UDCA‑based regimen is an effective alternative; if CDCA must be used, individualized risk–benefit assessment, informed consent, and consideration of partial or complete interruption of breastfeeding may be appropriate.europa+1