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Is mesalazine really safe for use in breastfeeding mothers?
  1. D A Silverman,
  2. J Ford,
  3. I Shaw,
  4. C S J Probert
  1. University of Bristol Division of Medicine, Bristol Royal Infirmary, Bristol, UK
  1. Correspondence to:
    Dr C S J Probert
    University of Bristol Division of Medicine, Bristol Royal Infirmary, Bristol BS2 8HW, UK; c.s.j.probertbristol.ac.uk

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Mesalazine containing preparations are commonly used for the treatment and maintenance of remission of inflammatory bowel disease. The young age of many inflammatory bowel disease sufferers means that the issue of whether to continue therapy in nursing mothers often arises.

We report a small study that was instigated after a nursing mother with Crohn’s disease approached us concerned about the safety of continuing to breastfeed while taking mesalazine. She had a cracked bleeding nipple and was worried about the dose of the drug that her baby would be receiving. We agreed to analyse the drug levels in milk from both of her breasts, and given the limited evidence in this area we designed a study to measure levels of mesalazine (5-ASA) and its metabolite (N-Ac-ASA) in breast milk from other nursing patients.

It is thought that maternal use of 5-ASA medication is safe for the breastfed infant although bloody diarrhoea in an infant being breast fed by a woman taking sulphasalazine has been reported,1 as has watery diarrhoea in the infant of a woman using 5-ASA suppositories.2 There has in fact been little research into excretion of 5-ASA and N-Ac-5-ASA in breast milk.

We obtained breast milk samples from four breastfeeding mothers with inflammatory bowel disease who were taking a 5-ASA preparation. Ethics approval for the study was obtained from the local ethics committee. Breast milk analysis was performed using high performance liquid chromatography. Concentrations of 5-ASA in the breast milk of 5-ASA treated patients were 4–40 ng/ml while those of N-Ac-5-ASA were 5.0–14.9 μg/ml (some 1000 times higher). These results are similar to levels found by other investigators.3–5

Based on an average intake of a breastfeeding infant of 150 ml of milk/kg of body weight/day, concentrations of 5-ASA found in breast milk samples equate to a dosage of 0.0006–0.006 mg/kg. This falls well below 10% of the standardised therapeutic dose, and therefore by this conventional criteria the effect of 5-ASA on the infant can be considered clinically unimportant. However, our finding of high levels of metabolite (N-Ac-5-ASA) in breast milk suggests that the metabolite is greatly enriched in breast milk. Differences in the physical properties of 5-ASA and N-Ac-5-ASA may well account in part for some difference in their rate of transfer into breast milk. But it is more likely that the findings reflect the result of active metabolism of 5-ASA taking place within the glandular cells of the breast.

We have shown that the concentration of 5-ASA in the breast milk of patients receiving 5-ASA therapy is low. It is therefore interesting to speculate whether the low levels of 5-ASA may, in part, be due to metabolism of 5-ASA to N-Ac-5-ASA by breast tissue as a mechanism to prevent high levels of active 5-ASA from accumulating in milk. N-Ac-5-ASA is a relatively inactive metabolite and is therefore unlikely to have a toxic effect on the infant, although to our knowledge the effect of N-Ac-5-ASA on infants has not been studied. We therefore cautiously support the view that 5-ASA containing medication is safe for breastfeeding mothers with inflammatory bowel disease. In addition to our specific findings relating to 5-ASA, the discovery of active drug metabolism in the breast has potentially wider implications. Based on our findings we would recommend that future studies looking at breast milk drug levels explore the possible effects of metabolism by breast tissue and the potential toxic effects of any metabolites produced.

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