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A06AX “Other drugs for constipation” comprises diverse agents that act via non‑traditional mechanisms (secretagogues, prokinetics, osmotic or gas‑producing effects) and, overall, can be used in breastfeeding with cautious, individualized risk–benefit assessment, favoring better‑characterized laxatives when possible.atcddd.fhi+9

Pharmacotherapeutic group and mechanisms

A06AX is defined within ATC code A06 “Drugs for constipation” as “Other drugs for constipation,” comprising agents that cannot be classified in preceding subgroups, including secretagogues and selective prokinetics.atcddd.fhi+2
The subgroup includes glycerol (A06AX01), carbon dioxide producing rectal preparations (A06AX02), lubiprostone (A06AX03), linaclotide (A06AX04), prucalopride (A06AX05), tegaserod (A06AX06), plecanatide (A06AX07), tenapanor (A06AX08) and elobixibat (A06AX09).atcddd.fhi+2

The WHO ATC/DDD Index provides defined daily doses for several A06AX agents, such as linaclotide 0.29 mg oral, while others (e.g. glycerol, carbon dioxide preparations) are used as single rectal doses rather than chronic daily therapy.atcddd.fhi

General toxicological profile

Because A06AX aggregates heterogeneous molecules, toxicology is agent‑specific, but class‑level patterns can be identified. Osmotic rectal agents (glycerol, carbon dioxide preparations) act locally, with minimal systemic absorption and low risk of systemic toxicity; adverse effects are primarily local irritation, rectal discomfort or, rarely, mechanical trauma. Secretagogues such as lubiprostone, linaclotide and plecanatide increase intestinal fluid secretion and accelerate transit, with common adverse effects including nausea, diarrhea, abdominal pain, distension and flatulence; dehydration and electrolyte disturbances are possible with severe diarrhea. Prokinetics like prucalopride and tegaserod stimulate gastrointestinal motility, so headache, abdominal pain, diarrhea and, for tegaserod, cardiovascular safety signals have influenced indications and availability. Newer agents (tenapanor, elobixibat) act via inhibition of transporters in the small intestine or ileum, and their toxicity profile includes diarrhea, abdominal discomfort and, for bile acid transporter inhibitors, possible elevations in liver tests.sps+4

Serious toxicity is uncommon at therapeutic doses but may occur in vulnerable populations: dehydration in patients with chronic diarrhea, electrolyte imbalance, worsening of inflammatory bowel disease, or, for older 5‑HT4 agonists, cardiovascular events. Overall, A06AX agents should be tailored to the underlying cause of constipation, comorbidities and concomitant medications.

Lactation‑toxicology considerations (subgroup overview)

General lactation guidance for laxatives emphasizes that most agents are minimally absorbed from the gastrointestinal tract and therefore result in low or negligible levels in breast milk, making many options compatible with breastfeeding.sps+1
Within A06AX, the lactation profile varies by mechanism and systemic exposure:

·        Glycerol (A06AX01) and carbon dioxide producing rectal preparations (A06AX02)
These rectal agents act locally with very limited systemic absorption, so transfer into breast milk is expected to be negligible; standard lactation references consider rectal glycerol and gas‑producing preparations acceptable during breastfeeding, with minimal infant risk.sps+1

·        Lubiprostone (A06AX03)
Lubiprostone is a locally acting intestinal chloride channel activator with low systemic bioavailability. No direct human lactation studies are available, but the manufacturer reports that lubiprostone and its metabolite were undetectable in rat milk, and it is not expected to cause adverse effects in breastfed infants; experts recommend monitoring the infant for diarrhea if the mother is treated.drugs+2

·        Linaclotide (A06AX04) and plecanatide (A06AX07)
These are peptide‑based guanylate cyclase‑C agonists with minimal systemic absorption and plasma concentrations below assay limits at therapeutic doses; although specific breast milk data are lacking, their poor oral bioavailability and peptide nature suggest very low infant exposure if any passes into milk. Standard practice treats them as likely low‑risk, but they are generally reserved for situations where first‑line laxatives have failed, with infant monitoring for diarrhea and dehydration.

·        Prucalopride (A06AX05)
Prucalopride is a selective 5‑HT4 agonist with systemic absorption and measurable presence in breast milk. Pharmacokinetic data show a milk‑to‑plasma AUC ratio of about 2.65:1, with an estimated infant dose of approximately 1.74 mcg/kg/day (around 6% of the maternal weight‑adjusted dose), representing minimal exposure below commonly used thresholds of concern. UK specialist pharmacy guidance states that prucalopride can be used with caution in breastfeeding, with preference for other laxatives first and infant monitoring for diarrhea. Some product information still advises against use during breastfeeding or recommends discontinuing either the drug or breastfeeding, reflecting regulatory caution in the absence of long‑term infant outcome data.drugs+3

·        Tegaserod (A06AX06), tenapanor (A06AX08), elobixibat (A06AX09)
For these newer or more restricted agents, robust human lactation data are lacking. Animal studies may show milk transfer, and given their systemic activity, manufacturers usually recommend avoiding use in breastfeeding or carefully weighing maternal benefit against unknown infant risks, with infant monitoring for gastrointestinal symptoms if use is unavoidable. Cardiovascular or other systemic safety considerations for tegaserod further limit its role in lactating women.

Overall, evidence supports the use of local, minimally absorbed laxatives (such as glycerol suppositories and some osmotic agents) as first‑line options in breastfeeding, with A06AX secretagogues and prokinetics reserved for refractory constipation after failure of safer alternatives and with appropriate infant surveillance.drugs+4

Clinical use in breastfeeding women

In breastfeeding women, constipation management should begin with dietary and lifestyle measures and laxatives that are well characterized as safe in lactation, such as bulk‑forming agents, osmotic preparations and stool softeners.sps+1
A06AX agents are generally considered when standard therapies have failed or are contraindicated; rectal glycerol and gas‑producing suppositories are widely accepted options due to negligible systemic absorption and minimal expected milk transfer.sps+1

Lubiprostone may be considered when chronic idiopathic constipation or opioid‑induced constipation persists despite first‑line treatments; given the undetectable rat milk levels and minimal systemic exposure, it is unlikely to pose significant infant risk, but breastfeeding references recommend infant monitoring for diarrhea and adherence to prescribed dosing. Prucalopride has more specific lactation pharmacokinetic data; with infant exposure around 6% of the maternal dose, it can be used with caution when clinically indicated, while avoiding unnecessary interruption of breastfeeding and monitoring the infant for changes in bowel pattern, feeding and weight gain.mayoclinic+5

Secretagogues such as linaclotide and plecanatide, and transporter inhibitors like tenapanor or elobixibat, should be reserved for cases where maternal benefit clearly outweighs theoretical infant risks, in consultation with specialists, because of limited lactation data. Documentation of maternal indication, treatment duration, and infant monitoring is advisable whenever A06AX agents are used in nursing mothers.