{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T07:18:35Z","timestamp":1773472715847,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T00:00:00Z","timestamp":1720310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.<\/jats:p>","DOI":"10.1038\/s41598-024-66380-8","type":"journal-article","created":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T15:01:18Z","timestamp":1720364478000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Risks of dairy derived excipients in medications for lactose intolerant and cow milk protein allergic patients"],"prefix":"10.1038","volume":"14","author":[{"given":"Alexandra","family":"Figueiredo","sequence":"first","affiliation":[]},{"given":"Maria Deolinda","family":"Auxtero","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Santo","sequence":"additional","affiliation":[]},{"given":"Andreia","family":"Casimiro","sequence":"additional","affiliation":[]},{"given":"Isabel Margarida","family":"Costa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,7,7]]},"reference":[{"key":"66380_CR1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/j.1365-2036.2008.03889.x","volume":"29","author":"P Eadala","year":"2009","unstructured":"Eadala, P., Waud, J. P., Matthews, S. B., Green, J. T. & Campbell, A. K. Quantifying the \u2018hidden\u2019 lactose in drugs used for the treatment of gastrointestinal conditions. Aliment. Pharmacol. Ther. 29, 677\u2013687 (2009).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"66380_CR2","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/2042098617751498","volume":"9","author":"D Mill","year":"2018","unstructured":"Mill, D., Dawson, J. & Johnson, J. L. Managing acute pain in patients who report lactose intolerance: The safety of an old excipient re-examined. Ther. Adv. Drug Saf. 9, 227\u2013235 (2018).","journal-title":"Ther. Adv. Drug Saf."},{"key":"66380_CR3","first-page":"496","volume":"21","author":"MT Audicana Berasategui","year":"2011","unstructured":"Audicana Berasategui, M. T. et al. Potential hypersensitivity due to the food or food additive content of medicinal products in Spain. J. Investig. Allergol. Clin. Immunol. 21, 496\u2013506 (2011).","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"66380_CR4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.15557\/PiMR.2018.0027","volume":"14","author":"Z Zdrojewicz","year":"2018","unstructured":"Zdrojewicz, Z., Zyskowska, K. & Wasiuk, S. Lactose in drugs and lactose intolerance\u2014Realities and myths. Pediatr. i Med. Rodz. 14, 261\u2013266 (2018).","journal-title":"Pediatr. i Med. Rodz."},{"key":"66380_CR5","first-page":"206","volume":"19","author":"J Robles","year":"2014","unstructured":"Robles, J. & Motheral, L. Hypersensitivity reaction after inhalation of a lactose-containing dry powder inhaler. J. Pediatr. Pharmacol. Ther. 19, 206\u2013211 (2014).","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"66380_CR6","doi-asserted-by":"crossref","unstructured":"Dominici, S. et al. Lactose: Characteristics, food and drug-related applications, and its possible substitutions in meeting the needs of people with lactose intolerance. Foods 11, (2022).","DOI":"10.3390\/foods11101486"},{"key":"66380_CR7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1590\/1678-457X.0019","volume":"36","author":"AHDN Rangel","year":"2016","unstructured":"Rangel, A. H. D. N. et al. Lactose intolerance and cow\u2019s milk protein allergy. Food Sci. Technol. 36, 179\u2013187 (2016).","journal-title":"Food Sci. Technol."},{"key":"66380_CR8","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S2468-1253(17)30154-1","volume":"2","author":"CL Storhaug","year":"2017","unstructured":"Storhaug, C. L., Fosse, S. K. & Fadnes, L. T. Country, regional, and global estimates for lactose malabsorption in adults: A systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 2, 738\u2013746 (2017).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"66380_CR9","doi-asserted-by":"publisher","first-page":"8020","DOI":"10.3390\/nu7095380","volume":"7","author":"Y Deng","year":"2015","unstructured":"Deng, Y., Misselwitz, B., Dai, N. & Fox, M. Lactose intolerance in adults: Biological mechanism and dietary management. Nutrients 7, 8020\u20138035 (2015).","journal-title":"Nutrients"},{"key":"66380_CR10","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1177\/2050640613484463","volume":"1","author":"B Misselwitz","year":"2013","unstructured":"Misselwitz, B. et al. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment. United Eur. Gastroenterol. J. 1, 151\u2013159 (2013).","journal-title":"United Eur. Gastroenterol. J."},{"key":"66380_CR11","doi-asserted-by":"publisher","first-page":"371","DOI":"10.2165\/00128072-200204060-00004","volume":"4","author":"S Pawar","year":"2002","unstructured":"Pawar, S. & Kumar, A. Issues in the formulation of drugs for oral use in children. Pediatr. Drugs 4, 371\u2013379 (2002).","journal-title":"Pediatr. Drugs"},{"key":"66380_CR12","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1136\/gutjnl-2019-318404","volume":"68","author":"B Misselwitz","year":"2019","unstructured":"Misselwitz, B., Butter, M., Verbeke, K. & Fox, M. R. Update on lactose malabsorption and intolerance: Pathogenesis, diagnosis and clinical management. Gut 68, 2080\u20132091 (2019).","journal-title":"Gut"},{"key":"66380_CR13","doi-asserted-by":"publisher","first-page":"E80","DOI":"10.1097\/MPG.0000000000002787","volume":"71","author":"ME Arancibia","year":"2020","unstructured":"Arancibia, M. E. et al. Association of cow\u2019s milk protein allergy prevalence with socioeconomic status in a cohort of Chilean infants. J. Pediatr. Gastroenterol. Nutr. 71, E80\u2013E83 (2020).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"issue":"5","key":"66380_CR14","doi-asserted-by":"publisher","first-page":"5025","DOI":"10.3390\/ijms24055025","volume":"24","author":"V Emmert","year":"2023","unstructured":"Emmert, V., Lendvai-Emmert, D., Eklics, K., Pr\u00e9musz, V. & T\u00f3th, G. P. Current practice in Pediatric cow\u2019s milk protein allergy-immunological features and beyond. Int. J. Mol. Sci. 24(5), 5025 (2023).","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"66380_CR15","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3390\/nu16030414","volume":"16","author":"A Darma","year":"2024","unstructured":"Darma, A., Sumitro, K. R., Jo, J. & Sitorus, N. Lactose intolerance versus cow\u2019s milk allergy in infants: A clinical dilemma. Nutrients 16(3), 414 (2024).","journal-title":"Nutrients"},{"key":"66380_CR16","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3390\/gels8070432","volume":"8","author":"M Kaur","year":"2022","unstructured":"Kaur, M. et al. Milk protein-based nanohydrogels: Current status and applications. Gels 8, 432 (2022).","journal-title":"Gels"},{"key":"66380_CR17","first-page":"91","volume":"90","author":"A Santoro","year":"2019","unstructured":"Santoro, A., Andreozzi, L., Ricci, G., Mastrorilli, C. & Caffarelli, C. Allergic reactions to cow\u2019s milk proteins in medications in childhood. Acta Biomed. 90, 91\u201393 (2019).","journal-title":"Acta Biomed."},{"key":"66380_CR18","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jaci.2003.11.015","volume":"113","author":"A Nowak-Wegrzyn","year":"2004","unstructured":"Nowak-Wegrzyn, A., Shapiro, G. & Beyer, K. Contamination of dry powder inhalers for. J. Allergy Clin. Immunol. 113, 558\u2013560 (2004).","journal-title":"J. Allergy Clin. Immunol."},{"key":"66380_CR19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/ajcn\/nqz104","volume":"110","author":"RA Forsg\u00e5rd","year":"2019","unstructured":"Forsg\u00e5rd, R. A. Lactose digestion in humans: Intestinal lactase appears to be constitutive whereas the colonic microbiome is adaptable. Am. J. Clin. Nutr. 110, 273\u2013279 (2019).","journal-title":"Am. J. Clin. Nutr."},{"key":"66380_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2022.949629","volume":"13","author":"R Tang","year":"2022","unstructured":"Tang, R. et al. Four clinical phenotypes of cow\u2019s milk protein allergy based on dairy product specific IgE antibody types in North China. Front. Immunol. 13, 1\u201310 (2022).","journal-title":"Front. Immunol."},{"key":"66380_CR21","doi-asserted-by":"publisher","first-page":"432","DOI":"10.2500\/aap.2012.33.3584","volume":"33","author":"CE Olivier","year":"2012","unstructured":"Olivier, C. E. et al. Is it just lactose intolerance?. Allergy Asthma Proc. 33, 432\u2013436 (2012).","journal-title":"Allergy Asthma Proc."},{"issue":"6","key":"66380_CR22","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.3390\/nu15061397","volume":"15","author":"C Cronin","year":"2023","unstructured":"Cronin, C., Ramesh, Y., De Pieri, C., Velasco, R. & Trujillo, J. \u2018Early introduction\u2019 of cow\u2019s milk for children with IgE-mediated cow\u2019s milk protein allergy: A review of current and emerging approaches for CMPA management. Nutrients 15(6), 1397 (2023).","journal-title":"Nutrients"},{"key":"66380_CR23","unstructured":"European Medicines Agency. Science Medicines Health. Inf. Packag. Leafl. Regarding Proline Used as an Excip. Med. Prod. Hum. Use. Sci. Med. Heal. 1\u201324 (2018)."},{"key":"66380_CR24","unstructured":"Stefani, G. P.; Higa, M.; Pastorino, A. C.; Castro, A. P. B. M.; Fomin, A. B. F.; & Jacob, C. M. A. Presen\u00e7a de corantes e lactose em medicamentos: avalia\u00e7\u00e3o de 181 produtos. Rev. Bras. Alerg. e Imunopatol. 18\u201326 (2009)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-66380-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-66380-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-66380-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T15:02:21Z","timestamp":1720364541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-66380-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,7]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["66380"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-66380-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,7]]},"assertion":[{"value":"16 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15631"}}