Use of Nonsteroidal Anti-Inflammatory Drugs and Acetaminophen During Lactation: A Systematic Review of Evidence and Prescribing Information

PURPOSE: Our objective was to update and organize information about the safety of using nonsteroidal anti-inflammatory drugs (NSAIDs) during lactation and assess whether the available information in the prescribing information (PI) of the approved drugs allows a health care professional to orient a lactating woman whether to use the drug. METHODS: For this systematic review, we searched MEDLINE, Embase, Cochrane, and LILACS for published articles from inception to 2024, reviewed the PI, and collected risk classifications for use during lactation for 23 NSAIDs from 5 widely available sources. No language restrictions were placed on the search. Data were synthesized, and the risk of bias and certainty of evidence were analyzed. A protocol was registered on the PROSPERO database (CRD42022295292). FINDINGS: We identified 3327 articles, removed 292 duplicates, and, after screening, retained 34 studies examining NSAID and acetaminophen excretion in breast milk and neonatal safety outcomes. Ten studies revealed acetaminophen, ibuprofen, flurbiprofen, mesalazine, and dipyrone adverse effects in infants. The relative infant dose was usually below 10%. Pharmacokinetic reasoning indicated that the infant must drink more milk than 150 ml/kg/d to reach the pediatric-approved dose. Only five PI of 16 NSAIDs approved in all jurisdictions had adequate information for decision making. The lists classifying the risks of drug use during lactation usually agree; however, they occasionally differ with the PI and each other, making it difficult to interpret. IMPLICATIONS: Despite recent efforts to adequate labeling, NSAIDs still lack enough data to establish whether lactating women should use them.