LACTOLOGY FOUNDATION

Antacids in ATC class A02AH are oral sodium bicarbonate preparations used for rapid neutralization of gastric acid, but they carry significant systemic toxicological risks and should be used cautiously in pregnancy and avoided during breastfeeding because they reach milk concentrations comparable to maternal plasma. From a toxico‑lactological perspective, safer alternatives exist for both pregnant and lactating women with dyspepsia or heartburn.

Classification and indications

Antacids with sodium bicarbonate are classified in the ATC system as A02AH, within the broader group of antacids used for acid‑related disorders of the alimentary tract. All oral formulations containing sodium bicarbonate, including those also indicated for metabolic acidosis, are classified in this subgroup.

These products are used mainly for short‑term relief of dyspepsia, heartburn and acid‑related epigastric discomfort, and in some cases are also used orally or parenterally in the management of metabolic acidosis and as part of specific antidotal protocols. In older literature they have also been used in conditions such as acute porphyria, though this indication is now uncommon.

Mechanism of action and milk transfer

Sodium bicarbonate acts as a systemic antacid; in the stomach it neutralizes hydrochloric acid to form sodium chloride, water and carbon dioxide, rapidly increasing intragastric pH. Because of its systemic absorption, sodium bicarbonate contributes a significant sodium load and can alter systemic acid–base balance, predisposing to metabolic alkalosis.

Sodium bicarbonate distributes widely and passes into breast milk, with reported milk to plasma ratios approximating 1:1 in neonates, which implies that breastfed infants may be exposed to concentrations similar to maternal plasma levels. This pattern of transfer underpins its assignment to a high‑risk lactation category (lactation category III), in which drug or metabolite levels in milk equal or exceed maternal plasma and clinically relevant toxicity in the nursing infant is plausible.

General toxicological profile

Even though sodium bicarbonate appears “benign”, its systemic effects can be clinically significant, especially with high doses, prolonged use, impaired renal function or in vulnerable populations such as neonates. Key dose‑related adverse effects include metabolic alkalosis, hypernatremia, fluid overload, hypokalemia and in some settings cerebral edema.

Metabolic alkalosis can manifest with neurological and neuromuscular symptoms (headache, confusion, muscle twitching, tetany, convulsions) and cardiorespiratory manifestations such as hypoventilation and arrhythmias. Excessive sodium load may precipitate or worsen hypertension, congestive heart failure and peripheral or pulmonary edema, especially in individuals with compromised cardiovascular or renal function.

Contraindications and precautions

Sodium bicarbonate should not be used in patients with metabolic or respiratory alkalosis, because it will further raise systemic pH and exacerbate the alkalemic state. It is also contraindicated in hypernatremia, hypocalcemia and significant chloride depletion (for example due to severe vomiting, diarrhea or cystic fibrosis), where additional bicarbonate and sodium can aggravate electrolyte imbalance and alkalosis.

Use is generally discouraged in clinically relevant renal impairment, because reduced bicarbonate and sodium excretion markedly increases the risk of hypernatremia, volume overload and severe alkalosis. Sodium bicarbonate must not be used as an antidote after ingestion of strong mineral acids, since neutralization is ineffective and vigorous gas formation can cause gastric distension and potential gastrointestinal perforation.

Toxicity in neonates and infants

Large oral or parenteral doses of sodium bicarbonate are particularly dangerous in neonates, especially preterm infants, because of their limited capacity to regulate fluid and electrolyte balance and cerebral perfusion. Documented complications include abrupt falls in intracranial pressure with subsequent intracranial hemorrhage, hypernatremia and, rarely, pulmonary edema, typically when very high doses have been administered.

Other reported toxic manifestations in neonates include flatulence, persistent hiccups, tetanic seizures, increased affinity of hemoglobin for oxygen at altered myocardial pH with potential myocardial necrosis, intracranial acidosis, the milk‑alkali syndrome and plasma hyperosmolality. These outcomes support a cautious or restrictive approach to maternal sodium bicarbonate use in the early neonatal period, particularly where breastfeeding continues.

Pregnancy risk assessment

For oral antacid use, regulatory labeling and clinical guidance are heterogeneous: some sources consider sodium bicarbonate “not recommended” in pregnancy because of sodium‑related fluid retention and potential maternal and fetal complications, while others allow its use if benefits clearly outweigh risks. Sodium bicarbonate antacids have historically been assigned to pregnancy category C, reflecting limited animal data and the absence of controlled human studies.

Main concerns in pregnancy include maternal fluid overload, exacerbation of pre‑existing hypertension or preeclampsia, and promotion of metabolic alkalosis, which can impair oxygen delivery to the fetus and potentially worsen fetal outcomes. Consequently, current guidance for heartburn and gastro‑oesophageal reflux in pregnancy generally prefers non‑systemic antacids, alginates, sucralfate, and when needed selected H2‑receptor antagonists or proton pump inhibitors, rather than sodium bicarbonate‑rich preparations.

Lactation risk assessment

Sodium bicarbonate is categorized as a high‑risk agent for lactation (lactation category III), because maternal ingestion results in milk concentrations roughly equivalent to plasma and meaningful infant exposure can be expected. Given the vulnerability of neonates to sodium and bicarbonate load, there is a realistic risk of hypernatremia, metabolic alkalosis, neurologic complications and, in extreme scenarios, intracranial hemorrhage or pulmonary edema in breastfed infants, especially if they are preterm.

Accordingly, some toxico‑lactological guidance recommends temporary interruption of breastfeeding during and for a period corresponding to complete elimination of sodium bicarbonate from the maternal circulation whenever high doses or repeated dosing are required. In contrast, general breastfeeding resources on indigestion emphasize that non‑systemic antacids and alginate combinations are usually compatible with breastfeeding and preferred over sodium bicarbonate‑dominant products.

Clinical recommendations and safer alternatives

From a toxico‑lactological standpoint, sodium bicarbonate‑based antacids in A02AH should be reserved for exceptional situations, used at the lowest effective dose and for the shortest possible duration, and avoided entirely in patients with the listed contraindications or significant comorbidities. Particular caution is essential when treating pregnant women with fluid retention or hypertension, mothers of preterm infants and neonates, and individuals with renal impairment or heart failure.

For both pregnancy and lactation, guideline‑consistent treatment of heartburn and dyspepsia favors lifestyle and dietary modification followed by non‑systemic antacids, alginate‑antacid combinations, sucralfate, and only then carefully selected H2 blockers or proton pump inhibitors, which have more reassuring reproductive and lactation safety profiles. Where sodium bicarbonate use is unavoidable during breastfeeding, a planned temporary cessation of breastfeeding with expression and discarding of milk until maternal plasma levels normalize is a rational risk‑mitigation strategy.