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Acetoxolone (ATC A02BX09) is an acetyl derivative of glycyrrhetinic acid used for peptic ulcer and gastroesophageal reflux disease, with wide therapeutic margin and limited but reassuring data for use in breastfeeding women when clinically indicated. Given its structural relationship to liquorice-derived glycyrrhetinic acid, exposure in pregnancy and lactation should remain conservative, but standard therapeutic dosing is unlikely to pose clinically relevant risk to a healthy term breastfed infant.file+4

Active substances and indications

Acetoxolone belongs to ATC class A02BX09, “other drugs for peptic ulcer and gastro-oesophageal reflux disease (GORD).” It is indicated for treatment of peptic ulcer disease of the stomach and duodenum and for gastroesophageal reflux disease, and is also used for erosive acute gastritis and bile‑related gastric mucosal irritation.medpedia.framar+4

Chemically, acetoxolone is an acetyl derivative of glycyrrhetinic (glycyrrhetic) acid, a triterpenoid compound naturally occurring in plants such as Echinophora lamellosa and related to liquorice constituents. It is characterized as a small‑molecule drug with an ATC classification under the alimentary tract and metabolism system.atcddd.fhi+4

Pharmacology and pharmacokinetics

Acetoxolone exerts anti‑ulcer and mucosal protective effects, consistent with the pharmacological profile of glycyrrhetinic acid derivatives used in peptic ulcer and GORD. The usual oral dosage for adults is in the range of 100–300 mg per day, reflecting a relatively modest daily exposure at therapeutic doses.pubchem.ncbi.nlm.nih+3

The compound has a wide therapeutic index; animal data report an approximate oral LD50 of 3400 mg/kg, indicating low acute toxicity compared with clinical doses. As a triterpenoid with relatively high molecular weight (around 512 Da), systemic distribution and tissue penetration occur, but extensive protein binding and metabolism can limit free drug levels.file+1

Toxicological profile

Experimental and clinical experience suggest that acetoxolone is generally well tolerated, with toxicity largely associated with the mineralocorticoid‑like effects known for glycyrrhetinic derivatives in cases of high or prolonged exposure (pseudoaldosteronism, hypokalemia, hypertension, edema, arrhythmias). Such adverse effects have been primarily described for liquorice/glycyrrhizic acid consumption rather than standard short‑term medicinal use, but they provide a theoretical basis for caution in patients with cardiovascular, renal, or electrolyte disorders.vkm+1

Because of its broad safety margin and high LD50, clinically significant toxicity at recommended doses for ulcer and GORD is considered unlikely in non‑pregnant adults without major comorbidities. Nonetheless, prolonged or supra‑therapeutic use may increase the risk of mineralocorticoid‑related adverse effects, particularly in susceptible individuals or in combination with other drugs affecting potassium balance.e-lactation+4

Use in pregnancy

Available classifications describe acetoxolone as belonging to pregnancy category A in systems analogous to historical FDA categories, indicating that controlled data have not shown increased fetal risk when used in pregnancy. However, by analogy with glycyrrhizic acid and liquorice, high oral exposure to related compounds during pregnancy has been associated with potential adverse effects on the fetus and long‑term outcomes in children, although data are too uncertain to define a clear “safe” threshold.vkm+1

Given these uncertainties, oral liquorice is generally discouraged during pregnancy, and acetoxolone, as a related derivative, should be used at the lowest effective dose and only when clearly indicated, particularly in women with pre‑existing hypertension or preeclampsia risk. Non‑pharmacological measures and better‑studied anti‑ulcer therapies remain preferred first‑line interventions in uncomplicated pregnancy‑related dyspepsia and reflux.fpnotebook+3

Pharmacokinetics in lactation

Specific quantitative data on acetoxolone concentrations in human breast milk are not available, and lactation pharmacokinetics must be inferred from its physicochemical properties and the behavior of glycyrrhetinic derivatives. With a molecular weight around 512 Da and lipophilic triterpenoid structure, some transfer into breast milk is plausible, but high plasma protein binding and metabolism tend to limit free drug levels and reduce effective milk exposure.medsafe+2

General lactation pharmacology principles indicate that most drugs with maternal milk levels corresponding to less than 10% of the weight‑adjusted maternal dose are considered compatible with breastfeeding, particularly when the infant is term and healthy. Based on these principles and the wide therapeutic margin of acetoxolone, even modest milk transfer is unlikely to approach toxic doses in the infant at standard maternal dosing.kellymom+2

Lactation safety assessment

The local monograph classifies acetoxolone as a toxico‑lactation category I drug, described as fully suitable for use during lactation, reflecting a favorable risk profile in breastfeeding women. This assessment aligns with broader observations that most medications, especially those with low relative infant doses and high therapeutic indices, are compatible with breastfeeding when used appropriately.medsafe+2

Nevertheless, glycyrrhizic and glycyrrhetinic acid derivatives have been associated with potential mineralocorticoid effects and, in rare cases of excessive maternal intake of liquorice‑containing preparations, significant neonatal lethargy and other adverse outcomes have been reported. Therefore, while routine therapeutic use of acetoxolone at standard doses appears low‑risk, it is prudent to avoid chronic high‑dose exposure and to monitor the breastfed infant for signs such as poor feeding, unusual lethargy, or fluid‑electrolyte imbalance if maternal use is prolonged.e-lactation+2

Practical recommendations for clinicians

When acetoxolone is considered for a breastfeeding woman, clinicians should first evaluate whether alternative anti‑ulcer or anti‑reflux therapies with more extensive lactation data might achieve the same therapeutic goal. If acetoxolone is chosen, it should be prescribed at the lowest effective dose and for the shortest duration consistent with symptom control, with attention to the mother’s blood pressure, electrolyte status, and concurrent medications that may influence potassium balance.fpnotebook+3

For healthy term infants, no routine interruption of breastfeeding is required when the mother receives standard doses of acetoxolone, and breastfeeding may continue with simple clinical observation. In preterm infants or those with significant comorbidities, or where high‑dose or long‑term maternal therapy is anticipated, additional caution and individualized risk–benefit assessment are advisable, with consideration of alternative therapies where feasible.kellymom+3