Last update: Jan. 15, 2019

Lamotrigine

Low Risk for breastfeeding


Moderately safe. Probably compatible.
Mild risk possible. Follow up recommended.
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An antiepileptic and sodium channel blocker which suppresses the release of glutamate. Indicated in epilepsies and prevention of depression from bipolar disorder type I (AEMPS 2018, GSK 2014).
Its use is authorized in children from 2 years old.
Oral administration (100 to 500 mg/day) in one or two daily doses. Therapeutic plasma levels vary between 2.5 and 15 mg/L (Mercadé 2012, Aldaz 2011, Morris 1998).

It is excreted in breastmilk in amounts which could be significant, with relatively high doses, between 9% and 20% (Kohn 2016, Domínguez 2015, Meador 2014, Sachs 2013, Fotopoulou 2009, Nordmo 2009, Newport 2008, Ivana 2007 , Page 2006, Ohman 2000, Rambeck 1997, Tomson 1997).

Plasma levels in infants whose mothers take lamotrigine are close to the lower therapeutic range and even within it (Clark 2013, Kacirova 2011, Fotopoulou 2009, Nordmo 2009, Ivana 2007, Page 2006, Liporace 2004, Ohman 2000, Rambeck 1997, Tomson 1997).
At birth, infant plasma levels are almost 90% of those of the mother, falling after a few weeks to 30% - 50% of maternal levels (Clark 2013, Newport 2008, Ivana 2007, Page 2006, Liporace 2004), indicating that exposure during breastfeeding is much lower than during pregnancy.

During pregnancy the clearance of lamotrigine and other antiepileptic drugs increases, reducing plasma levels, which is why the dose must be increased (Harden 2009, Sabers 2009, Petrenaite 2005, de Haan 2004). After childbirth levels increase rapidly and can cause problems for mother and newborn if maternal plasma levels are not monitored by reducing the maternal dose to the previous one before pregnancy (Paulzen 2018, Fotopoulou 2009, Nordmo 2009, O'Connor 2009, Haan 2004, Ohman 2000, Tomson 1997).

Sedation, hypotonia and no-weight gain have been observed in up to 4.5% of infants whose mothers were taking this medication (Soussan 2014), especially in the neonatal period. An apnea crisis was reported in a 16-day-old infant whose mother was taking a high dose (850 mg/day) of lamotrigine (Nordmo 2009), anemia was reported in a 40-day-old infant possibly due to maternal lamotrigine (Bedussi 2018), asymptomatic thrombocytosis (Newport 2008) and self-limited exanthem (Wakil 2009).

A case of a 13-day-old infant with marked drowsiness and hypotonia was reported, with exclusive breastfeeding (direct and expressed due to drowsiness) and good weight gain, whose mother was taking 400 mg of lamotrigine daily and had plasma levels of 13.4 mg/L (in high therapeutic range). The symptomatology disappeared after halting breastfeeding for 48 hours.

A published case of severe hypernatremic dehydration in a 12-day newborn is not easily attributable to maternal lamotrigine. The mother, who had bipolar disorder, was also taking sertraline, aripripazole (which can cause hypogalactia), levothyroxine, naproxen, docusate, acetaminophen and codeine (Morin 2017).

An infant of a month and a half whose mother was taking lamotrigine had withdrawal syndrome when she was abruptly weaned (Popescu 2005).

In the short and long term, no side effects or alterations in physical and neurological development have been observed in dozens of infants whose mothers were treated with lamotrigine (Levesque 2017, Prakash 2016, Domínguez 2015, Grover 2015, Meador 2014 and 2010, Veiby 2013, Wakil 2009, Newport 2008, Page 2006, Gentile 2005, Liporace 2004, Ohman 2000, Rambeck 1997, Tomson 1997), including mothers of premature babies (Précourt 2011), which is why several medical associations, experts and expert consensus consider the use of this medication to be compatible with breastfeeding (Hale 2019, Vajda 2014, Davanzo 2013, Veiby 2013, Rowe 2013, Mercadé 2012, Précourt 2011, Madadi 2010), and it is not necessary to halt breastfeeding if a mother requires lamotrigine, especially if the daily 500mg dose is not exceeded (Kohn 2016).

Lamotrigine levels in the neonate should be measured and possible side effects in the neonatal period should be monitored: sedation, poor diet (Crettenand 2018, Briggs 2017, Reimers 2014, Davanzo 2013, Rowe 2013, Précourt 2011, Madadi 2010, Ivana 2007, Pack 2006, Crawford 2005, Liporace 2004), and the maternal dose can be reduced to a minimum effective dose and/or temporarily establishing partial breastfeeding (O'Brien 2005) if the levels reach the therapeutic range.

Alternatives

Suggestions made at e-lactancia are done by APILAM´s pediatricians and pharmacists, and are based on updated scientific publications.
It is not intended to replace the relationship you have with your doctor but to compound it.

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Other names

Lamotrigine in other languages or writings:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 98 %
Molecular weight 256 daltons
Protein Binding 55 %
VD 0,9 - 1,2 l/Kg
pKa 5,7 -
Tmax 2, 5 (1,4 - 4,8) hours
T1/2 33 (12 - 59) hours
M/P ratio 0,4 - 0,77 -
Theoretical Dose 0,8 - 1,8 mg/Kg/d
Relative Dose 9 - 20 %

References

  1. Hale TW. Hale's Medications & Mothers' Milk. Springer Publishing Company. 2019
  2. Crettenand M, Rossetti AO, Buclin T, Winterfeld U. [Use of antiepileptic drugs during breastfeeding : What do we tell the mother?] Nervenarzt. 2018 Abstract
  3. Bedussi F, Relli V, Faraoni L, Eleftheriou G, Giampreti A, Gallo M, Lorenzi F, Sangiovanni A, Chiara F, Maccioni R, Pilloni PP, Falchi G, Scanu M, Butera R, Bacis G. Normocytic Normochromic Anaemia and Asymptomatic Neutropenia in a 40-Day-Old Infant Breastfed by an Epileptic Mother Treated With Lamotrigine: Infant's Adverse Drug Reaction. J Paediatr Child Health. 2018 Abstract
  4. AEMPS. Lamotrigina. Ficha técnica. 2018 Full text (in our servers)
  5. Paulzen M, Stingl JC, Augustin M, Saßmannshausen H, Franz C, Gründer G, Schoretsanitis G. Comprehensive Measurements of Intrauterine and Postnatal Exposure to Lamotrigine. Clin Pharmacokinet. 2018 Abstract
  6. Levesque S, Riley C. Fetal exposure to lamotrigine and quetiapine in two consecutive pregnancies. Arch Womens Ment Health. 2017 Abstract
  7. Morin C, Chevalier I. Severe Hypernatremic Dehydration and Lower Limb Gangrene in an Infant Exposed to Lamotrigine, Aripiprazole, and Sertraline in Breast Milk. Breastfeed Med. 2017 Abstract
  8. Briggs GG, Freeman RK, Towers CV, Forinash AB. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Wolters Kluwer Health. 11th edition (acces on line) 2017
  9. Jacob S, Nair AB. An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs. Drugs R D. 2016 Abstract Full text (link to original source) Full text (in our servers)
  10. Prakash C, Hatters-Friedman S, Moller-Olsen C, North A. Maternal and Fetal Outcomes After Lamotrigine Use in Pregnancy: A Retrospective Analysis from an Urban Maternal Mental Health Centre in New Zealand. Psychopharmacol Bull. 2016 Abstract Full text (link to original source) Full text (in our servers)
  11. Kohn E, Brandriss N, Soback S, Bar-Haim A, Berkovitch M. Levetiracetam and lamotrigine excretion in breast milk. Reprod Toxicol. 2016;60:184. 2016
  12. Domínguez Vázquez I, Imaz M, Soy D, Torra M, Torres A, Martín-Santos R, García Esteve L. Transferencia de lamotrigina a través de la lactancia materna. XVIII Congreso Nacional de Psiquiatría. Santiago de Compostela. PO 1012. 2015 Full text (in our servers)
  13. Grover S, Avasthi A. Mood stabilizers in pregnancy and lactation. Indian J Psychiatry. 2015 Abstract Full text (link to original source) Full text (in our servers)
  14. Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study Group. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA Pediatr. 2014 Abstract Full text (link to original source) Full text (in our servers)
  15. Reimers A. New antiepileptic drugs and women. Seizure. 2014 Abstract Full text (link to original source) Full text (in our servers)
  16. GSK. Lamotrigine. Drug Summary. 2014 Full text (in our servers)
  17. Soussan C, Gouraud A, Portolan G, Jean-Pastor MJ, Pecriaux C, Montastruc JL, Damase-Michel C, Lacroix I. Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database. Eur J Clin Pharmacol. 2014 Abstract
  18. Bernard N, Gouraud A, Paret N, Cottin J, Descotes J, Vial T. Azathioprine and breastfeeding: long-term follow-up. Fundam Clin Pharmacol. 2013;27 (Suppl 1):12. Abstract 05-03. Lacroix I, Soussan C, Portolan G, Montastruc JL. Drug-induced adverse reactions via breastfeeding: a study in the French Pharmacovigilance Database Fundam Clin Pharmacol. 2013;27 (Suppl 1):42-43. Abstract 26-01. Abstracts of the 17th Annual Meeting of French Society of Pharmacology and Therapeutics. Fundam Clin Pharmacol. 2013;27 (Suppl 1) p 12 y 42-43 2013 Abstract Full text (link to original source) Full text (in our servers)
  19. Davanzo R, Dal Bo S, Bua J, Copertino M, Zanelli E, Matarazzo L. Antiepileptic drugs and breastfeeding. Ital J Pediatr. 2013 Abstract Full text (link to original source) Full text (in our servers)
  20. Rowe H, Baker T, Hale TW. Maternal medication, drug use, and breastfeeding. Pediatr Clin North Am. 2013 Feb;60(1):275-94. Abstract
  21. Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol. 2013 Abstract Full text (link to original source) Full text (in our servers)
  22. Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Abstract Full text (link to original source) Full text (in our servers)
  23. Sachs HC; Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013 Sep;132(3):e796-809. Abstract Full text (link to original source) Full text (in our servers)
  24. Mercadé Cerdá JM, Sancho Rieger J, Mauri Llerda JA, López González FJ,Salas Puig X. Guías diagnósticas y terapéuticas de la Sociedad Española de Neurología 2012. 1. Guía oficial de práctica clínica en epilepsia. Guías SEN 2012 Full text (in our servers)
  25. Aldaz A, Ferriols R, Aumente D, Calvo MV, Farre MR, García B, Marqués R, Mas P, Porta B, Outeda M, Soy D; Grupo PK-gen de la Sociedad Española de Farmacia Hospitalaria.. Monitorización farmacocinética de antiepilépticos. [Pharmacokinetic monitoring of antiepileptic drugs]. Farm Hosp. 2011 Abstract Full text (link to original source) Full text (in our servers)
  26. Kacirova I, Grundmann M, Brozmanova H. Serum levels of lamotrigine in breastfeeding mothers, maternal milk and nursed infants. Basic Clin Pharmacol Toxicol. 2011;109:134. Poster 239. 2011 Abstract Full text (link to original source) Full text (in our servers)
  27. Precourt A, Morin C. Use of lamotrigine during breastfeeding: descriptive analysis of our population and report of five cases of premature neonates. Breastfeed Med. 2011;6 (Suppl 1):S-18. Poster 35. 2011
  28. Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010 Abstract Full text (link to original source) Full text (in our servers)
  29. Madadi P, Ito S. Perinatal exposure to maternal lamotrigine: clinical considerations for the mother and child. Can Fam Physician. 2010 Abstract Full text (link to original source) Full text (in our servers)
  30. Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol. 2009 Abstract
  31. Nordmo E, Aronsen L, Wasland K, Småbrekke L, Vorren S. Severe apnea in an infant exposed to lamotrigine in breast milk. Ann Pharmacother. 2009 Abstract
  32. Wakil L, Epperson CN, Gonzalez J, O'Reardon JP, Kim DR. Neonatal outcomes with the use of lamotrigine for bipolar disorder in pregnancy and breastfeeding: a case series and review of the literature. Psychopharmacol Bull. 2009 Abstract
  33. Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of... Neurology. 2009 Abstract Full text (link to original source) Full text (in our servers)
  34. O'Connor SE, Zupanc ML. Women and epilepsy. J Pediatr Pharmacol Ther. 2009 Abstract Full text (link to original source) Full text (in our servers)
  35. Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res. 2009 Abstract
  36. Newport DJ, Pennell PB, Calamaras MR, Ritchie JC, Newman M, Knight B, Viguera AC, Liporace J, Stowe ZN. Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics. 2008 Abstract Full text (link to original source) Full text (in our servers)
  37. Ivana K, Milan G, Blanka K, Hana B. Therapeutic monitoring of lamotrigine during delivery, in the neonatal period, and during lactation. Ther Drug Monit. 2007;29:477. Abstract 53. 2007
  38. Page-Sharp M, Kristensen JH, Hackett LP, Beran RG, Rampono J, Hale TW, Kohan R, Ilett KF. Transfer of lamotrigine into breast milk. Ann Pharmacother. 2006 Abstract
  39. Gentile S. Lamotrigine in pregnancy and lactation. Arch Womens Ment Health. 2005 Abstract
  40. Petrenaite V, Sabers A, Hansen-Schwartz J. Individual changes in lamotrigine plasma concentrations during pregnancy. Epilepsy Res. 2005 Abstract
  41. Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia. 2005 Abstract Full text (link to original source) Full text (in our servers)
  42. O'Brien MD, Gilmour-White SK. Management of epilepsy in women. Postgrad Med J. 2005 Abstract Full text (link to original source) Full text (in our servers)
  43. Popescu L, Marceanu M, Moleavin I. Withdrawal of lamotrigine caused by sudden weaning of a newborn: a case report. Epilepsia. 2005;46 (Suppl 6):407. Poster 1351. 2005 Abstract Full text (in our servers)
  44. Liporace J, Kao A, D'Abreu A. Concerns regarding lamotrigine and breast-feeding. Epilepsy Behav. 2004 Abstract
  45. de Haan GJ, Edelbroek P, Segers J, Engelsman M, Lindhout D, Dévilé-Notschaele M, Augustijn P. Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology. 2004 Abstract
  46. Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia. 2000 Abstract Full text (link to original source) Full text (in our servers)
  47. Morris RG, Black AB, Harris AL, Batty AB, Sallustio BC. Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service. Br J Clin Pharmacol. 1998 Abstract Full text (link to original source) Full text (in our servers)
  48. Rambeck B, Kurlemann G, Stodieck SR, May TW, Jürgens U. Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child. Eur J Clin Pharmacol. 1997 Abstract
  49. Tomson T, Ohman I, Vitols S. Lamotrigine in pregnancy and lactation: a case report. Epilepsia. 1997 Abstract Full text (link to original source) Full text (in our servers)

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