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Drug Levels

Mesalamine (5-aminosalicylic acid; 5-ASA) is metabolized to N-acetyl-5-ASA, which is inactive in treating inflammatory bowel disease, but the metabolite’s possible effects on the breastfed infant are unknown.

Maternal Levels. One woman with ulcerative colitis (time postpartum not stated) was taking delayed-release tablets of mesalamine (Claversal) 500 mg orally 3 times daily. A single milk sample taken 5.25 hours after a dose contained 0.11 mg/L of mesalamine and 12.4 mg/L of N-acetyl-5-ASA.[7]

A woman with inactive ulcerative colitis was taking mesalamine (product not specified) 1 gram orally 3 times daily. A milk sample taken 1 week postpartum at 5 hours after a dose contained mesalamine 0.1 mg/L and N-acetyl-5-ASA 18.1 mg/L. Another milk sample taken 4 days later at 5 hours after a dose contained mesalamine 0.1 mg/L and N-acetyl-5-ASA 12.3 mg/L. The authors also report another mother taking 1 g of mesalamine daily (product not specified) who had a milk level of mesalamine that was undetectable and N-acetyl-5-ASA level of 2.2 mg/L (time of sampling and assay method not reported). The authors estimated that a fully breastfed infant whose mother was taking 1.5 grams of mesalamine daily would receive 0.015 mg/kg of mesalamine and 2.3 mg/kg of N-acetyl-5-ASA daily.[8]

Twelve women taking mesalamine in various oral dosage forms and one taking olsalazine capsules collected 1 to 8 breastmilk samples over one day at 2 to 4 weeks postpartum. Mesalamine was undetectable (< 20 mcg/L) in most women, but detected in the milk of 3 women; one was taking Pentasa tablets 1 gram 3 times daily and one was taking Pentasa suppositories 1 gram at night and one was taking oral Asacol 400 mg twice daily plus Mesalal tablets 500 mg at night. Mesalamine milk levels ranged from 20 to 81 mcg/L. N-acetyl-5-ASA was detected in all milk samples, but there was no clear relationship between the dosages, times of the doses and the peak time in breastmilk. The individual average N-acetyl-5-ASA milk levels by product and dosage were Asacol tablets 800 mg daily, 0.24 mg/L (1 patient); Asacol tablets 800 mg daily plus Mesalal tablets 500 mg at night, 2.6 mg/L (1 patient); Mesalal tablets 500 mg daily, 0.75 mg/L (1 patient); Pentasa tablets 500 mg daily, 0.97 mg/L (1 patient); Pentasa tablets 1.5 grams daily, 2.8 to 6.5 mg/L (5 patients); Pentasa tablets 2 grams daily, 10.5 mg/L (1 patient); Pentasa tablets 3 grams daily, 10.2 mg/L (1 patient); Pentasa suppositories 1 gram daily, 1.9 mg/L (1 patient). Using the highest individual measured of 16.2 mg/L, the authors estimated that a fully breastfed infant would receive about 15 mg of N-acetyl-5-ASA daily, which is 1% of the usual daily dosage (not weight-adjusted) of mesalamine.[9]

Four women with inflammatory bowel disease who were breastfeeding during mesalamine use had breastmilk samples taken. Specific dosages and mesalamine products were not reported nor were sampling times with respect to the doses. Mesalamine milk levels ranged from 4 to 40 mcg/L and N-acetyl-5-ASA milk levels ranged from 5 to 14.9 mg/L. The authors calculated a daily dosage of mesalamine of 0.6 to 6 mcg/kg daily in an exclusively breastfed infant. However, the N-acetyl-5-ASA dosage would be about 1000 times greater. The authors speculated that mesalamine might be metabolized in the breast to N-acetyl-5-ASA in the breast tissue, but provided no direct evidence of this happening.[10]

Ten exclusively nursing mothers who were receiving long-term treatment for inflammatory bowel disease with a delayed-release form of mesalamine (2 Asacol HD, 8 Lialda) provided milk samples at 0, 1, 2, 4, 8, 12, and 24 hours after a dose. The women were 35 to 251 days postpartum and their once-daily doses ranged from 1.2 to 4.8 grams. Milk mesalamine levels were highly variable among the participants and the N-acetyl-5-ASA metabolite was not measured. The average infant dosage was 15.7 mcg/kg daily (range 1.8 to 76.8 mcg/kg daily) and the mean percentage of weight-adjusted maternal dose was 0.02% (range 0.01 to 0.085%).[11]

Infant Levels. Relevant published information was not found as of the revision date.