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

Bedussi, Francesca; Relli, Valentina; Faraoni, Lorella; Eleftheriou, Georgios; Giampreti, Andrea; Gallo, Mariapina; Lorenzi, Federica; Sangiovanni, Anna; Chiara, Francesca De; Maccioni, Rosella; Pilloni, Pier P; Falchi, Giovanna; Scanu, Mariapiera; Butera, Raffaella; Bacis, Giuseppe

doi:10.1111/jpc.13805

Cited by 10 publications

(4 citation statements)

References 4 publications

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“…The UAR serves as a metric to identify outlying infants with exposure as demonstrated using the infant predicted 95th percentile in AUC ∞ . To date, adverse effects were observed in three breastfed infants (12,16, and 40 day olds) from mothers who were taking lamotrigine (38,49,55). In this study, the presented UARs demonstrated that lamotrigine exposure through breastfeeding can reach levels similar to those in mothers taking 200 mg, although the probability is likely to be low.…”

Section: Discussionmentioning

confidence: 63%

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

Yeung

Itô

Autmizguine

et al. 2021

AAPS J

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Current methods to assess risk in infants exposed to maternal medication through breast milk do not specifically account for infants most vulnerable to high drug exposure. A workflow applied to lamotrigine incorporated variability in infant anatomy and physiology, milk intake volume, and milk concentration to predict infant exposure. An adult physiologically based pharmacokinetic model of lamotrigine was developed and evaluated. The model was scaled to account for growth and maturation of a virtual infant population (n=100). Daily infant doses were simulated using milk intake volume and concentration models described by a nonlinear equation of weight-normalized intake across infant age and a linear function on the relationship of observed milk concentrations and maternal doses, respectively. Average infant plasma concentration at steady state was obtained through simulation. Models were evaluated by comparing observed to simulated infant plasma concentrations from breastfeeding infants based on a 90% prediction interval (PI). Upper AUC ratio (UAR) was defined as a novel risk metric. Twenty-five paired (milk concentrations measured) and 18 unpaired (milk concentrations unknown) infant plasma samples were retrieved from the literature. Forty-four percent and 11% of the paired and unpaired infant plasma concentrations were outside of the 90% PI, respectively. Over all ages (0-7 months), unpaired predictions captured more observed infant plasma concentrations within 90% PI than paired. UAR was 0.18-0.44 when mothers received 200 mg lamotrigine, suggesting that infants can receive 18-44% of the exposure per dose as compared to adults. UARs determined for further medications could reveal trends to better classify at-risk mother-infant pairs.

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Section: Discussionmentioning

confidence: 63%

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

Yeung

Itô

Autmizguine

et al. 2021

AAPS J

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“…Adverse effects of breastfeeding have rarely been reported. However, there is one case report of episodes of apnea in a breastfed infant [38] and one case of anemia at 40 days after birth, which normalized after stopping breastfeeding [39].…”

Section: Lamotriginementioning

confidence: 99%

“…Based on 92 published cases, the lamotrigine milk/maternal serum concentration ratios have ranged from 0.18 to 1.4, with averages in most studies in the order of 0.6 to 0.7 [29][30][31][32][33][34]. Infant/maternal serum concentration ratios were reported in 166 mother-child pairs, and ranged from 0.2 to 0.9, with a reported average in individual studies in most cases at around 0.3 [29][30][31][32][34][35][36][37][38][39]. Adverse effects of breastfeeding have rarely been reported.…”

Section: Lamotriginementioning

confidence: 99%

Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force

Tomson,

Battino,

Bromley

et al. 2022

Epileptic Disorders

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We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short-and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.

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“…On the other hand, there are case reports of serious adverse effects in breastfed infants attributed to pharmacological treatment of the mother [ 4 , 5 ], which is why a careful risk-benefit evaluation must be performed for each medicine.…”

Section: Introductionmentioning

confidence: 99%

Medicines postpartum in Sweden and coverage in Janusmed Breastfeeding

Asplund

Sköld²,

Lind³

et al. 2023

Eur J Clin Pharmacol

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Purpose The purpose of this article is (1) to investigate which medicines are prescribed and dispensed to women the first 6 months postpartum, (2) to identify medicines dispensed postpartum but not recommended during breastfeeding, and (3) to find medicines commonly dispensed postpartum, but not currently included in Janusmed Breastfeeding. Methods In this register-based cohort study covering births between January 2017 and August 2019, the Swedish Medical Birth Register (MBR), the Prescribed Drug Register, and Janusmed Breastfeeding were linked to identify medicines dispensed to women during the first 6 months postpartum, and how they are covered and classified in Janusmed Breastfeeding. Results During the first 6 months postpartum, 66% of women purchased at least one prescription medicine from the pharmacy. The most common medicines were contraceptive agents, analgesics, antibiotics, and glucocorticoids. A third of the 30 most commonly dispensed medicines have no information available about the safety of use in breastfeeding. The most dispensed medicines, where the database advises against use in breastfeeding, included several antitussive agents, a local anaesthetic, and several gestagens. The most commonly dispensed medicines not covered by the Janusmed Breastfeeding were medicines for dry eyes, for assisted reproduction, and HIV. Conclusion Prescribed medicines compatible with breastfeeding are more common during the first 6 months postpartum than medicines not compatible with breastfeeding, but medicines which lack evidence for safety in breastfeeding are still commonly used.

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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

Cited by 10 publications

References 4 publications

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

Incorporating Breastfeeding-Related Variability with Physiologically Based Pharmacokinetic Modeling to Predict Infant Exposure to Maternal Medication Through Breast Milk: a Workflow Applied to Lamotrigine

Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force

Medicines postpartum in Sweden and coverage in Janusmed Breastfeeding

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