Also known as Aconip, Indocin, Indometacin, Indometacina, Indometacine, Indometacinum
A synthetic nonsteroidal indole derivative with anti-inflammatory activity and chemopreventive properties. As a nonsteroidal anti-inflammatory drug (NSAID), indomethacin inhibits the enzyme cyclooxygenase, thereby preventing cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines. This agent also may inhibit the expression of multidrug-resistant protein type 1, resulting in increased efficacies of some antineoplastic agents in treating multi-drug resistant tumors. In addition, indomethacin activates phosphatases that inhibit the migration and proliferation of cancer cells and downregulates survivin, which may result in tumor cell apoptosis. (NCI04)
Originator: NCI Thesaurus | Source: The website of the National Cancer Institute (http://www.cancer.gov)
Can I take Indomethacin while breastfeeding?
Because of the low levels of indomethcin in breastmilk and therapeutic administration directly to infants, it is acceptable to use in nursing mothers. However, other agents with more published information on use during lactation may be preferable, especially while nursing a newborn or preterm infant.
Drug levels
Maternal Levels. In one study, 15 women who were less than 1 week postpartum took indomethacin in dosages ranging from 75 mg orally to 300 mg rectally daily (0.94 to 4.29 mg/kg daily). Milk samples were taken before and after feeding at times ranging from 0.7 to 21.4 hours after the last dose. In 11 of the women, indomethacin was undetectable (<20 mcg/L) in milk. Assuming that undetectable milk levels had the concentration of the assay limit, the average dosage excreted in milk was 0.27% of maternal weight-adjusted dosage.[1] However, the excretion of the glucuronide metabolite into milk was not measured and it could be absorbed as indomethacin by a newborn. Eight women donated milk on days 4, 12 and 26 postpartum for an in vitro measurement of protein binding and lipid partitioning of indomethacin in milk. Results were used to estimate passage into milk using physicochemical principles. The authors calculated that a breastfed infant would receive about 0.5% of the maternal weight-adjusted dosage or about 3% of the neonatal dose used to treat patent ductus arteriosus with a maternal dosage of 75 mg daily.[2] This study did not account for possible contribution to the infant’s dosage by the glucuronide metabolite. Infant Levels. In 6 of 7 infants breastfed during maternal indomethacin use of 75 mg orally to 300 mg rectally daily, the drug was undetectable (<20 mcg/L) in plasma. One infant had a plasma level of 47 mcg/L at 1.2 hours after the midpoint of the breastfeed. This infant's mother was taking 2.94 mg/kg daily of indomethacin and had a milk indomethacin level of 111 mcg/L 2.3 hours after the dose.[1]
Effects in breastfed infants
Maternal Levels. In one study, 15 women who were less than 1 week postpartum took indomethacin in dosages ranging from 75 mg orally to 300 mg rectally daily (0.94 to 4.29 mg/kg daily). Milk samples were taken before and after feeding at times ranging from 0.7 to 21.4 hours after the last dose. In 11 of the women, indomethacin was undetectable (<20 mcg/L) in milk. Assuming that undetectable milk levels had the concentration of the assay limit, the average dosage excreted in milk was 0.27% of maternal weight-adjusted dosage.[1] However, the excretion of the glucuronide metabolite into milk was not measured and it could be absorbed as indomethacin by a newborn. Eight women donated milk on days 4, 12 and 26 postpartum for an in vitro measurement of protein binding and lipid partitioning of indomethacin in milk. Results were used to estimate passage into milk using physicochemical principles. The authors calculated that a breastfed infant would receive about 0.5% of the maternal weight-adjusted dosage or about 3% of the neonatal dose used to treat patent ductus arteriosus with a maternal dosage of 75 mg daily.[2] This study did not account for possible contribution to the infant’s dosage by the glucuronide metabolite. Infant Levels. In 6 of 7 infants breastfed during maternal indomethacin use of 75 mg orally to 300 mg rectally daily, the drug was undetectable (<20 mcg/L) in plasma. One infant had a plasma level of 47 mcg/L at 1.2 hours after the midpoint of the breastfeed. This infant's mother was taking 2.94 mg/kg daily of indomethacin and had a milk indomethacin level of 111 mcg/L 2.3 hours after the dose.[1]
Possible effects on lactation
Relevant published information was not found as of the revision date.
Alternate drugs to consider
Acetaminophen, Flurbiprofen, Ibuprofen, Naproxen, Piroxicam
References
1. Lebedevs TH, Wojnar-Horton RE, Yapp P et al. Excretion of indomethacin in breast milk. Br J Clin Pharmacol. 1991;32:751-4. PMID: 1768569
2. Beaulac-Baillargeon L, Allard G. Distribution of indomethacin in human milk and estimation of its milk to plasma ratio in vitro. Br J Clin Pharmacol. 1993;36:413-6. PMID: 12959288
3. Eeg-Olofsson O, Malmros I, Elwin CE, Steen B. Convulsions in a breast-fed infant after maternal indomethacin. Lancet. 1978;2 (8082):215. Letter. PMID: 78421
Last Revision Date
20160401
Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.
Source: LactMed – National Library of Medicine (NLM)