{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:41:38Z","timestamp":1772232098744,"version":"3.50.1"},"reference-count":46,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:p>OBJECTIVE. Although lamotrigine use during pregnancy has substantially increased over the past decade secondary to accumulated reproductive safety data, systematic data on lamotrigine during breastfeeding remains sparse. We sought to characterize the determinants of lamotrigine concentrations in breast milk and nursing-infant plasma.<\/jats:p>\n                  <jats:p>PATIENTS AND METHODS. Women who enrolled in a prospective investigation of perinatal medication pharmacokinetics, were treated with lamotrigine, and chose to continue lamotrigine while breastfeeding were included in the analysis. Breast milk samples were collected via breast pump from foremilk to hindmilk from a single breast to determine the excretion gradient and serial samples over 24 hours to determine the time course of excretion. Paired maternal\/infant plasma samples were also collected. Lamotrigine concentrations in all of the samples were determined by using high-performance liquid chromatography with ultraviolet detection. Statistical analyses of breast milk and infant plasma concentrations and their determinants were conducted.<\/jats:p>\n                  <jats:p>RESULTS. Thirty women and their nursing infants participated in the study, providing a total of 210 breast milk samples. The mean milk\/plasma ratio was 41.3%. There was a nonsignificant trend for higher lamotrigine concentrations in breast milk 4 hours after the maternal dose. Infant plasma concentrations were 18.3% of maternal plasma concentrations. The theoretical infant lamotrigine dose was 0.51 mg\/kg per day, and the relative infant lamotrigine dose was 9.2%. Mild thrombocytosis was present in 7 of 8 infants at the time of serum sampling. No other adverse events were observed or reported in the breastfed infants.<\/jats:p>\n                  <jats:p>CONCLUSIONS. Consistent with previous investigations of medications in breast milk, the lamotrigine milk\/plasma ratio is highly variable. The rate of lamotrigine excretion into human breast milk is similar to that observed with other antiepileptic drugs. These data expand the extant literature on lamotrigine in breastfeeding and demonstrate relatively comparable nursing-infant exposure to lamotrigine compared with other antiepileptic drugs.<\/jats:p>","DOI":"10.1542\/peds.2007-3812","type":"journal-article","created":{"date-parts":[[2008,6,30]],"date-time":"2008-06-30T20:24:44Z","timestamp":1214857484000},"page":"e223-e231","source":"Crossref","is-referenced-by-count":95,"title":["Lamotrigine in Breast Milk and Nursing Infants: Determination of Exposure"],"prefix":"10.1542","volume":"122","author":[{"given":"D. Jeffrey","family":"Newport","sequence":"first","affiliation":[{"name":"Departments of Psychiatry and Behavioral Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Page B.","family":"Pennell","sequence":"additional","affiliation":[{"name":"Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha R.","family":"Calamaras","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Behavioral Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanee","family":"Newman","sequence":"additional","affiliation":[{"name":"Neurology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Knight","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Behavioral Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adele C.","family":"Viguera","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurologic Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Liporace","sequence":"additional","affiliation":[{"name":"Center for Neuroscience, Riddle Memorial Hospital, Media, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary N.","family":"Stowe","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Behavioral Sciences"},{"name":"Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2021120905573000100_R1","doi-asserted-by":"crossref","unstructured":"Pennell PB. Using current evidence in selecting antiepileptic drugs for use during pregnancy. Epilepsy Curr.2005;5(2):45\u201351","DOI":"10.1111\/j.1535-7597.2005.05201.x"},{"key":"2021120905573000100_R2","doi-asserted-by":"crossref","unstructured":"Yonkers KA, Wisner K, Stowe ZN, et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry.2004;161(4):608\u2013620","DOI":"10.1176\/appi.ajp.161.4.608"},{"key":"2021120905573000100_R3","doi-asserted-by":"crossref","unstructured":"Newport DJ, Stowe ZN, Viguera AC, et al. Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord.2008;10(3):432\u2013436","DOI":"10.1111\/j.1399-5618.2007.00565.x"},{"key":"2021120905573000100_R4","doi-asserted-by":"crossref","unstructured":"Vajda FJ, O'Brien T, Hitchcock A, Graham J, Lander C. Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months. J Clin Neurosci.2003;10(5):543\u2013549","DOI":"10.1016\/S0967-5868(03)00158-9"},{"key":"2021120905573000100_R5","doi-asserted-by":"crossref","unstructured":"Sabers A, Dam M, A-Rogvi-Hansen B, et al. Epilepsy and pregnancy: lamotrigine as main drug used. Acta Neurol Scand.2004;109(1):9\u201313","DOI":"10.1034\/j.1600-0404.2003.00200.x"},{"key":"2021120905573000100_R6","doi-asserted-by":"crossref","unstructured":"Cunnington M, Tennis P; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Lamotrigine and the risk of malformations in pregnancy. Neurology.2005;64(6):955\u2013960","DOI":"10.1212\/01.WNL.0000154515.94346.89"},{"key":"2021120905573000100_R7","unstructured":"GlaxoSmithKline Corp. International Lamotrigine Pregnancy Registry: Interim Report (1 September 1992 Through 31 March 2007). Wilmington, NC: Inveresk;2007"},{"key":"2021120905573000100_R8","unstructured":"Holmes LB, Wyszynski DF, Baldwin EJ, Haebecker E, Glassman LH, Smith CR. Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine during pregnancy [abstract]. Birth Defects Res Part A: Clin Mol Teratol.2006;76(5):318"},{"key":"2021120905573000100_R9","doi-asserted-by":"crossref","unstructured":"Meador KJ, Baker GA, Finnell RH, et al. In utero antiepileptic drug exposure: fetal death and malformations. Neurology.2006;67(3):407\u2013412","DOI":"10.1212\/01.wnl.0000227919.81208.b2"},{"key":"2021120905573000100_R10","doi-asserted-by":"crossref","unstructured":"Morrow J, Russell A, Guthrie E, et al. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatr.2006;77(2):193\u2013198","DOI":"10.1136\/jnnp.2005.074203"},{"key":"2021120905573000100_R11","doi-asserted-by":"crossref","unstructured":"Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia.2000;41(6):709\u2013713","DOI":"10.1111\/j.1528-1157.2000.tb00232.x"},{"key":"2021120905573000100_R12","doi-asserted-by":"crossref","unstructured":"Myllynen PK, Pienimaki PK, Vahakangas KH. Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo. Eur J Clin Pharmacol.2003;58(10):677\u2013682","DOI":"10.1007\/s00228-002-0544-4"},{"key":"2021120905573000100_R13","doi-asserted-by":"crossref","unstructured":"Ragan K, Stowe ZN, Newport DJ. The use of antidepressants and mood stabilizers in breast feeding women. In: Cohen LS, Nonacs RM, eds. Mood and Anxiety Disorders During Pregnancy and Postpartum. Washington DC: American Psychiatric Publishing, Inc;2005:105\u2013144","DOI":"10.1176\/appi.books.9781615377640.lg05"},{"key":"2021120905573000100_R14","doi-asserted-by":"crossref","unstructured":"Tomson T. Gender aspects of pharmacokinetics of new and old AEDs: pregnancy and breast-feeding. Ther Drug Monit.2005;27(6):718\u2013721","DOI":"10.1097\/01.ftd.0000179843.63515.8f"},{"key":"2021120905573000100_R15","unstructured":"Hale TW. Medications in Mothers Milk. 12th ed. Amarillo, TX: Hale Publishing;2006"},{"key":"2021120905573000100_R16","doi-asserted-by":"crossref","unstructured":"Rambeck B, Kurlemann G, Stodieck SR, May TW, Jurgens U. Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child. Eur J Clin Pharmacol.1997;51(6):481\u2013484","DOI":"10.1007\/s002280050234"},{"key":"2021120905573000100_R17","doi-asserted-by":"crossref","unstructured":"Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation: a case report. Epilepsia.1997;38(9):1039\u20131041","DOI":"10.1111\/j.1528-1157.1997.tb01489.x"},{"key":"2021120905573000100_R18","doi-asserted-by":"crossref","unstructured":"Liporace J, Kao A, D'Abreu A. Concerns regarding lamotrigine and breast-feeding. Epilepsy Behav.2004;5(1):102\u2013105","DOI":"10.1016\/j.yebeh.2003.11.018"},{"key":"2021120905573000100_R19","doi-asserted-by":"crossref","unstructured":"Page-Sharp M, Kristensen JH, Hackett LP, et al. Transfer of lamotrigine into breast milk. Ann Pharmacother.2006;40(7\u20138):1470\u20131471","DOI":"10.1345\/aph.1G667"},{"key":"2021120905573000100_R20","doi-asserted-by":"crossref","unstructured":"Gow PJ, Ghabrial H, Smallwood RA, Morgan DJ, Ching MS. Neonatal hepatic drug elimination. Pharmacol Toxicol.2001;88(1):3\u201315","DOI":"10.1034\/j.1600-0773.2001.088001003.x"},{"key":"2021120905573000100_R21","unstructured":"American Academy of Neurology. Practice Parameter: Management Issues for Women With Epilepsy (Summary Statement): Report of the Quality Standards Subcommittee of the American Academy of Neurology. St Paul, MN: American Academy of Neurology;1998"},{"key":"2021120905573000100_R22","doi-asserted-by":"crossref","unstructured":"Stowe ZN, Owens MJ, Landry JC, et al. Sertraline and desmethylsertraline in human breast milk and nursing infants. Am J Psychiatry.1997;154(9):1255\u20131260","DOI":"10.1176\/ajp.154.9.1255"},{"key":"2021120905573000100_R23","doi-asserted-by":"crossref","unstructured":"Stowe ZN, Cohen LS, Hostetter A, Ritchie JC, Owens MJ, Nemeroff CB. Paroxetine in breast milk and nursing infants. Am J Psychiatry.2000;157(2):185\u2013189","DOI":"10.1176\/appi.ajp.157.2.185"},{"key":"2021120905573000100_R24","doi-asserted-by":"crossref","unstructured":"Stowe ZN, Hostetter A, Owens MJ, et al. Pharmacokinetics of sertraline excretion into human breast milk: defining infant exposure. J Clin Psychiatry.2003;64(1):73\u201380","DOI":"10.4088\/JCP.v64n0114"},{"key":"2021120905573000100_R25","doi-asserted-by":"crossref","unstructured":"Hostetter AL, Stowe ZN, Cox M, Ritchie JC. A novel system for the determination of antidepressant concentrations in human breast milk. Ther Drug Monit.2004;26(1):47\u201352","DOI":"10.1097\/00007691-200402000-00011"},{"key":"2021120905573000100_R26","doi-asserted-by":"crossref","unstructured":"Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk. Clinical pharmacokinetic considerations. Clin Pharmacokinet.1988;14(4):217\u2013140","DOI":"10.2165\/00003088-198814040-00003"},{"key":"2021120905573000100_R27","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics, Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics.2001;108(3):776\u2013789","DOI":"10.1542\/peds.108.3.776"},{"key":"2021120905573000100_R28","doi-asserted-by":"crossref","unstructured":"Suri R, Stowe ZN, Hendrick V, Hostetter A, Widawski M, Altshuler LL. Estimates of nursing infant daily dose of fluoxetine through breast milk. Biol Psychiatry.2002;52(5):446\u2013451","DOI":"10.1016\/S0006-3223(02)01368-9"},{"key":"2021120905573000100_R29","doi-asserted-by":"crossref","unstructured":"Bennett PN. Use of the monographs on drugs. In: Bennett PN, ed. Drugs and Human Lactation. 2nd ed. Amsterdam, Netherlands: Elsevier;1996:67\u201374","DOI":"10.1016\/B978-044481981-9\/50024-2"},{"key":"2021120905573000100_R30","doi-asserted-by":"crossref","unstructured":"Barr PA, Buettiker VE, Antony JH. Efficacy of lamotrigine in refractory neonatal seizures. Pediatr Neurol.1999;20(2):161\u2013163","DOI":"10.1016\/S0887-8994(98)00125-8"},{"key":"2021120905573000100_R31","doi-asserted-by":"crossref","unstructured":"Mikati MA, Fayad M, Koleilat M, et al. Efficacy, tolerability, and kinetics of lamotrigine in infants. J Pediatr.2002;141(1):31\u201335","DOI":"10.1067\/mpd.2002.125256"},{"key":"2021120905573000100_R32","doi-asserted-by":"crossref","unstructured":"Pin\u0303a-Garza JE, Levisohn P, Gucuyener K, et al. Adjunctive lamotrigine for partial seizures in patients 1\u201324 months old. Neurology.2007; In press","DOI":"10.1212\/01.wnl.0000285493.08622.35"},{"key":"2021120905573000100_R33","doi-asserted-by":"crossref","unstructured":"Pynnonen S, Sillanpaa M. Letter: carbamazepine and mother's milk. Lancet.1975;2(7934):563","DOI":"10.1016\/S0140-6736(75)90950-2"},{"key":"2021120905573000100_R34","doi-asserted-by":"crossref","unstructured":"Pynnonen S, Kanto J, Sillanpaa M, Erkkola R. Carbamazepine placental transport, tissue concentrations in foetus and newborn, and level in milk. Acta Pharmacol Toxicol.1977;41(3):244\u2013253","DOI":"10.1111\/j.1600-0773.1977.tb02145.x"},{"key":"2021120905573000100_R35","doi-asserted-by":"crossref","unstructured":"Merlob P, Mor N, Litwin A. Transient hepatic dysfunction in an infant of an epileptic mother treated with carbamazepine during pregnancy and breastfeeding. Ann Pharmacother.1992;26(12):1563\u20131565","DOI":"10.1177\/106002809202601215"},{"key":"2021120905573000100_R36","doi-asserted-by":"crossref","unstructured":"Brent NB, Wisner KL. Fluoxetine and carbamazepine concentrations in a nursing mother\/infant pair. Clin Pediatr (Phila).1998;37(1):41\u201344","DOI":"10.1177\/000992289803700107"},{"key":"2021120905573000100_R37","unstructured":"Kuhnz W, Jager-Roman E, Rating D, et al. Carbamazepine and carbamazepine-10,11-epoxide during pregnancy and postnatal period in epileptic mothers and their nursed infants: pharmacokinetics and clinical effects. Pediatr Pharmacol.1983;3(3\u20134):199\u2013208"},{"key":"2021120905573000100_R38","doi-asserted-by":"crossref","unstructured":"Frey B, Braegger CP, Ghelfi D. Neonatal cholestatic hepatitis from carbamazepine exposure during pregnancy and breast feeding. Ann Pharmacother.2002;36(4):644\u2013647","DOI":"10.1345\/aph.1A326"},{"key":"2021120905573000100_R39","doi-asserted-by":"crossref","unstructured":"Froescher W, Eichelbaum M, Niesen M, Dietrich K, Rausch P. Carbamazepine levels in breast milk. Ther Drug Monit.1984;6(3):266\u2013271","DOI":"10.1097\/00007691-198409000-00002"},{"key":"2021120905573000100_R40","doi-asserted-by":"crossref","unstructured":"Stahl MM, Neiderud J, Vinge E. Thrombocytopenic purpura and anemia in a breast-fed infant whose mother was treated with valproic acid. J Pediatr.1997;130(6):1001\u20131003","DOI":"10.1016\/S0022-3476(97)70292-0"},{"key":"2021120905573000100_R41","doi-asserted-by":"crossref","unstructured":"Alexander FW. Sodium valproate and pregnancy. Arch Dis Child.1979;54(3):240","DOI":"10.1136\/adc.54.3.240"},{"key":"2021120905573000100_R42","doi-asserted-by":"crossref","unstructured":"von Unruh GE, Froescher W, Hoffmann F, Niesen M. Valproic acid in breast milk: how much is really there?Ther Drug Monit.1984;6(3):272\u2013276","DOI":"10.1097\/00007691-198409000-00003"},{"key":"2021120905573000100_R43","doi-asserted-by":"crossref","unstructured":"Piontek CM, Baab S, Peindl KS, Wisner KL. Serum valproate levels in 6 breastfeeding mother-infant pairs. J Clin Psychiatry.2000;61(3):170\u2013172","DOI":"10.4088\/JCP.v61n0304"},{"key":"2021120905573000100_R44","doi-asserted-by":"crossref","unstructured":"Dame C, Sutor AH. Primary and secondary thrombocytosis in childhood. Br J Haemotol.2005;129(2):165\u2013177","DOI":"10.1111\/j.1365-2141.2004.05329.x"},{"key":"2021120905573000100_R45","doi-asserted-by":"crossref","unstructured":"McPherson RJ, Juul S. Patterns of thrombocytosis and thrombocytopenia in hospitalized neonates. J Perinatol.2005;25(3):166\u2013172","DOI":"10.1038\/sj.jp.7211230"},{"key":"2021120905573000100_R46","doi-asserted-by":"crossref","unstructured":"Finch E, Lorber J. Methaemoglobinaemia in the newborn: probably due to phenytoin excreted in human milk. J Obstet Gynaecol Br Emp.1954;61(6):833\u2013834","DOI":"10.1111\/j.1471-0528.1954.tb07739.x"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/122\/1\/e223\/1069021\/zpe0070800e223.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/122\/1\/e223\/1069021\/zpe0070800e223.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T17:14:18Z","timestamp":1738257258000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/122\/1\/e223\/73023\/Lamotrigine-in-Breast-Milk-and-Nursing-Infants"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,1]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,7,1]]},"published-print":{"date-parts":[[2008,7,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2007-3812","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1120038.576165","asserted-by":"object"}]},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,1]]}}}