Levetiracetam in lactation: How much is excreted into human breast milk?

Dinavitser, Natalie; Kohn, Elkana; Berlin, Maya; Brandriss, Nurit; Bar‐Chaim, Adina; Keidar, Ran; Livné, Avinoam; Stepensky, David; Berkovitch, Matitiahu; Sheinberg, Revital

doi:10.1111/bcp.14940

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…246,247,[253][254][255] Data about levetiracetam come from a recent study of 20 breastfeeding women and 21 infants. 256 Infant levetiracetam exposure via the breast milk was close to the safety thresholds and the adverse effect commonly reported is somnolence.…”

Section: Therapeutic Advances In Neurological Disordersmentioning

confidence: 74%

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Nucera

Brigo

Trinka

et al. 2022

Ther Adv Neurol Disord

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Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of in utero-exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.

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Section: Therapeutic Advances In Neurological Disordersmentioning

confidence: 74%

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Nucera

Brigo

Trinka

et al. 2022

Ther Adv Neurol Disord

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“…Available information on maternal serum and milk concentrations as well as on serum concentrations in breastfed infants is extensive. Based on 82 published cases, the levetiracetam milk/maternal serum concentration ratios have ranged from 0.58 to 1.79, with averages in most studies in the order of 1.0 [27, 42-45]. Infant/maternal serum concentration ratios were reported in 121 mother‐child pairs, and ranged from below the level of quantification in infant serum to a ratio of 0.71, with a reported average in individual studies in most cases at around 0.1 [14, 27, 42-45].…”

Section: Resultsmentioning

confidence: 99%

“…However, there is a case report of hypotonia in one of eight breastfed infants [42]. Three cases of sedation were reported among 16 children breastfed by mothers taking levetiracetam, which resolved shortly after switching to partial breastfeeding [45]. A large prospective study, of which 84 breastfeeding women were on levetiracetam, did not show overall adverse effects at age two years across all ASMs [46].…”

Section: Resultsmentioning

confidence: 99%

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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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“…However, a small number of infants experienced somnolence, poor diet and other symptoms after contacting levetiracetam in breast milk. Fortunately, these adverse reactions returned to normal soon after breastfeeding was stopped ( 53 , 54 ).…”

Section: Metabolic Pathway Of Asms and The Influence Of Asms In Human...mentioning

confidence: 99%

Management of anti-seizure medications in lactating women with epilepsy

et al. 2022

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Epilepsy is a common neurological disease. At present, there are about 70 million epilepsy patients in the world, half of them are women, and 30–40% of women with epilepsy are of childbearing potential. Patients with epilepsy who are of childbearing potential face more challenges, such as seizures caused by hormonal fluctuations and the risk of adverse effects on the mother and baby from taking anti-seizure medications (ASMs). Breast milk is one of the best gifts that a mother can give her baby, and breastfeeding can bring more benefits to the baby. Compared with healthy people, people with epilepsy have more concerns about breastfeeding because they are worried that ASMs in their milk will affect the growth and development of the baby, and they are always faced with the dilemma of whether to breastfeed after childbirth. Regarding, whether women with epilepsy can breastfeed while taking ASMs, and whether breastfeeding will adversely affect the baby is still an important topic of concern for patients and doctors. This article reviews the existing research on breastfeeding-related issues in women with epilepsy to guide clinical practice, and improve the breastfeeding compliance of women with epilepsy.

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Levetiracetam in lactation: How much is excreted into human breast milk?

Cited by 8 publications

References 17 publications

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide

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

Management of anti-seizure medications in lactating women with epilepsy

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