{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:42:59Z","timestamp":1755794579652,"version":"3.44.0"},"reference-count":35,"publisher":"Springer Publishing Company","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatal Network"],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:p>Nonpharmacologic management is the first-line therapy for infants experiencing neonatal opioid withdrawal syndrome (NOWS) and\/or neonatal abstinence syndrome (NAS). Currently, the most prescribed first-line pharmacologic agent is an opioid, most often morphine, but methadone and buprenorphine are preferred by some providers. For some infants, an opioid, along with maximized nonpharmacologic strategies, does not provide adequate symptom relief and a second-line agent is needed. Phenobarbital and clonidine are two commonly prescribed second-line agents for the management of NOWS\/NAS. This column will describe these two commonly prescribed second-line agents.<\/jats:p>","DOI":"10.1891\/nn-2024-0059","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T22:05:20Z","timestamp":1755295520000},"page":"271-276","source":"Crossref","is-referenced-by-count":0,"title":["Second-Line Medications for Neonatal Opioid Withdrawal Syndrome\/Neonatal Abstinence Syndrome"],"prefix":"10.1891","volume":"44","author":[{"given":"Susan Givens","family":"Bell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"793","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"issue":"2","key":"2025081515050940000_44.4.271.1","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2023-062871","article-title":"Advances in the care of infants with prenatal opioid exposure and neonatal opioid withdrawal syndrome","volume":"153","year":"2024","journal-title":"Pediatrics"},{"key":"2025081515050940000_44.4.271.2","unstructured":"Centers for Disease Control and Prevention. Opioid use during pregnancy: treat and manage infants affected by prenatal opioid exposure. Centers for Disease Control and Prevention; 2024. Accessed January 24, 2025. https:\/\/www.cdc.gov\/opioid-use-during-pregnancy\/treatment\/infants-opioid.html"},{"key":"2025081515050940000_44.4.271.3","unstructured":"Shukla S , Zirkin LB , Pomar G . Perinatal drug abuse and neonatal drug withdrawal. In: StatPearls [Internet] . StatPearls Publishing; 2023. Accessed January 24, 2025. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK519061\/"},{"key":"2025081515050940000_44.4.271.4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjebm-2020-111432"},{"key":"2025081515050940000_44.4.271.5","doi-asserted-by":"crossref","first-page":"2050313X20952981","DOI":"10.1177\/2050313X20952981","article-title":"Venlafaxine-induced encephalopathy in term newborn","volume":"8","year":"2020","journal-title":"SAGE Open Med Case Rep"},{"key":"2025081515050940000_44.4.271.6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.24991"},{"key":"2025081515050940000_44.4.271.7","unstructured":"Mississippi State Department of Health. COVID-19 and neonatal hospitalization related to maternal substance use in Mississippi: an escalating crisis. 2022. Accessed January 30, 2025. https:\/\/msdh.ms.gov\/page\/resources\/19423.pdf"},{"issue":"5","key":"2025081515050940000_44.4.271.8","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2020-029074","article-title":"Neonatal opioid withdrawal syndrome","volume":"146","year":"2020","journal-title":"Pediatrics"},{"key":"2025081515050940000_44.4.271.9","unstructured":"DrugBank Online. Phenobarbital. 2025. Accessed January 30, 2025. https:\/\/go.drugbank.com\/drugs\/DB01174"},{"issue":"9","key":"2025081515050940000_44.4.271.10","first-page":"752854","article-title":"Use of phenobarbital to treat neonatal abstinence syndrome from exposure to single vs. multiple substances","volume":"9","year":"2021","journal-title":"Front Pediatr"},{"issue":"1","key":"2025081515050940000_44.4.271.11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/17425255.2021.1837112","article-title":"Pharmacotherapy of neonatal opioid withdrawal syndrome: a review of pharmacokinetics and pharmacodynamics","volume":"17","year":"2021","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2025081515050940000_44.4.271.12","unstructured":"UCSF Northern California Neonatology Consortium. Consensus guideline for management of neonatal opioid syndrome (NOWS) & drug-exposed infants. UCSF Benioff Children\u2019s Hospital; 2024. Accessed October 24, 2024. https:\/\/medconnection.ucsfbenioffchildrens.org\/news\/consensus-guidelines-for-management-of-neonatal-opioid-withdrawal-syndrome-nows-and-drug-exposed-infants"},{"key":"2025081515050940000_44.4.271.13","unstructured":"Jansson L . Neonatal abstinence syndrome (NAS): Management and outcome. UpToDate; 2024. Accessed October 24, 2024. https:\/\/www-uptodate-com.usfhl.idm.oclc.org\/contents\/neonatal-abstinence-syndrome-nas-management-and-outcome"},{"key":"2025081515050940000_44.4.271.14","unstructured":"Migone C , Bustin A , Brutus N , et al. Inpatient clinical pathway for evaluation and treatment of infants with neonatal abstinence syndrome (NAS)\/neonatal opioid withdrawal syndrome (NOWS). Children\u2019s Hospital of Philadelphia Clinical Pathways Program; 2021. Accessed October 24, 2024. https:\/\/pathways.chop.edu\/clinical-pathway\/neonatal-abstinence-syndrome-nas-neonatal-opioid-withdrawal-syndrome-nows-clinical-pathway"},{"key":"2025081515050940000_44.4.271.15","unstructured":"Fung C . Neonatal abstinence syndrome: What you need to know [PowerPoint Presentation]. University of Utah, Department of Pediatrics; 2018. Accessed February 6, 2025. https:\/\/physicians.utah.edu\/sites\/g\/files\/zrelqx276\/files\/media\/documents\/2021\/2018-02-09-neonatal-abstinance-syndrome1.pdf"},{"key":"2025081515050940000_44.4.271.16","unstructured":"Boston Medical Center. NOWS secondary agent algorithm. Boston Medical Center NOWS Protocol . 2022. Accessed February 6, 2025. https:\/\/pnqinma.org\/wp-content\/uploads\/2024\/04\/I2-Boston-Medical-Center-NOWS-Protocol.pdf"},{"key":"2025081515050940000_44.4.271.17","unstructured":"Clouser A , Dierod E . Harmful excipients for pediatric patients. Contemp Pediatr . 2022;39(1). Accessed February 3, 2025. https:\/\/www.contemporarypediatrics.com\/view\/harmful-excipients-for-pediatric-patients"},{"key":"2025081515050940000_44.4.271.18","unstructured":"Merative Micromedex. Phenobarbital. 2025. Accessed February 6, 2025. https:\/\/www.micromedexsolutions.com\/micromedex2\/librarian\/PFActionId\/evidencexpert.GetNeofaxDrugMonograph?navitem=neofaxDrugMonographDocRetrieval&drugName=PHENobarbital&tabSelected=neonatal"},{"issue":"3","key":"2025081515050940000_44.4.271.19","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1208\/s12249-008-9112-2","article-title":"Development and chemical stability studies of alcohol-free phenobarbital solution for use in pediatrics: a technical note","volume":"9","year":"2008","journal-title":"AAPS PharmSciTech"},{"issue":"12","key":"2025081515050940000_44.4.271.20","first-page":"747745","article-title":"Efficacy and safety of levetiracetam vs. phenobarbital for neonatal seizures: A systematic review and meta-analysis","volume":"12","year":"2021","journal-title":"Front Neurol"},{"key":"2025081515050940000_44.4.271.21","doi-asserted-by":"crossref","unstructured":"Gwartney T , D\u2019Apolito K , Harris JB . Neonatal abstinence syndrome. In: Jahn AJ , McPherson C , eds. Fetal and Neonatal Pharmacology for the Advanced Practice Nurse . Springer Publishing; 2023. Accessed October 25, 2024. https:\/\/doi.org\/10.1891\/9780826158840","DOI":"10.1891\/9780826158840.0009"},{"issue":"10","key":"2025081515050940000_44.4.271.22","first-page":"e47980","article-title":"Neonatal abstinence syndrome: An insight over impact of maternal substance use","volume":"15","year":"2023","journal-title":"Cureus"},{"key":"2025081515050940000_44.4.271.23","unstructured":"Yasaei R , Saadabadi A . Clonidine. In: StatPearls . StatPearlsPublishing; 2022. Accessed February 2, 2025. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK459124\/"},{"key":"2025081515050940000_44.4.271.24","unstructured":"Memorial Sloan Kettering Cancer Center. Clonidine. Patient and Caregiver Information; 2022. Accessed February 2, 2025. https:\/\/www.mskcc.org\/pdf\/cancer-care\/patient-education\/medications\/pediatric\/clonidine"},{"issue":"5","key":"2025081515050940000_44.4.271.25","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2023-065610","article-title":"Clonidine as monotherapy for neonatal opioid withdrawal syndrome: a randomized trial","volume":"154","year":"2024","journal-title":"Pediatrics"},{"issue":"3","key":"2025081515050940000_44.4.271.26","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2020-017830","article-title":"Phenobarbital and clonidine as secondary medications for neonatal opioid withdrawal syndrome","volume":"147","year":"2021","journal-title":"Pediatrics"},{"key":"2025081515050940000_44.4.271.27","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2013.95"},{"key":"2025081515050940000_44.4.271.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41372-020-0685-2"},{"key":"2025081515050940000_44.4.271.29","unstructured":"National Institutes of Health, National Library of Medicine. Phenobarbital elixir. DAILYMED. Accessed October 26, 2024. https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=120a0542-7fd8-429e-aada-a936cc65b1f8"},{"key":"2025081515050940000_44.4.271.30","unstructured":"National Institutes of Health, National Library of Medicine. Phenobarbital oral solution. DAILYMED. Accessed October 26, 2024. https:\/\/dailymed.nlm.nih.gov\/dailymed\/drugInfo.cfm?setid=45f6317e-cfc9-4ec9-84c9-72daa6c68911"},{"issue":"11","key":"2025081515050940000_44.4.271.31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0260279","article-title":"Stability evaluation of compounded clonidine hydrochloride oral liquids based on a solid-phase extraction HPLC-UV method","volume":"16","year":"2021","journal-title":"PLoS One"},{"key":"2025081515050940000_44.4.271.32","unstructured":"Pharmacy Services, Nationwide Children\u2019s. Clonidine oral. Compounding Formulas. Accessed October 26, 2024. https:\/\/www.nationwidechildrens.org\/specialties\/pharmacy-services\/compounding-formulas"},{"key":"2025081515050940000_44.4.271.33","doi-asserted-by":"publisher","DOI":"10.1007\/s13181-020-00814-3"},{"key":"2025081515050940000_44.4.271.34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2214470"},{"key":"2025081515050940000_44.4.271.35","doi-asserted-by":"crossref","unstructured":"Zankl A , Martin J , Davey JG , Osborn DA . Opioid treatment for opioid withdrawal in newborn infants. Cochrane Database Syst Rev . 2021.CD002059 https:\/\/doi.org\/10.1002\/14651855.CD002059.pub4","DOI":"10.1002\/14651858.CD002059.pub4"}],"container-title":["Neonatal Network"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1891\/NN-2024-0059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T22:05:31Z","timestamp":1755295531000},"score":1,"resource":{"primary":{"URL":"http:\/\/connect.springerpub.com\/lookup\/doi\/10.1891\/NN-2024-0059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8,14]]},"published-print":{"date-parts":[[2025,8,1]]}},"alternative-id":["10.1891\/NN-2024-0059"],"URL":"https:\/\/doi.org\/10.1891\/nn-2024-0059","relation":{},"ISSN":["0730-0832","1539-2880"],"issn-type":[{"value":"0730-0832","type":"print"},{"value":"1539-2880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]}}}