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Antiepileptics
4.8.1
Introduction
All antiepileptics pass into the milk, albeit in differing amounts. Babies who are breastfed during maternal antiepileptic treatment apparently develop just as well as those who are not breastfed. At least, that is what was reported in one study of 82 mother–infant pairs in which breastfeeding was carried out during monotherapy with lamotrigine , carbamazepine , phenytoin or valproate by comparison to 112 non-breastfed infants of mothers undergoing antiepileptic treatment. Both groups were already exposed in utero . IQs were compared at the age of 3 years. The authors discuss why the experimentally observed apoptotic effect of some antiepileptics did not lead to measurable anomalies in the immature brain after exposure through the mother’s milk and submit that either the intrauterine outweighed the postnatal effect (although in animal experiments, the postnatal sensitivity for such damage is no less), breastfeeding causes a counter-effect or the significantly lower concentration via the mother’s milk is insufficient for such side effects ( ).
With monotherapy, nothing in most antiepileptics argues against exclusive breastfeeding. However, in individual cases, intolerance cannot be ruled out (see under the individual antiepileptics). When a combination therapy with more than one antiepileptic is required, it must be individually decided whether the baby should be supplemented or even weaned to reduce the exposure. For vitamin-K prophylaxis in the newborn period, see Chapter 2.9 . For individual antiepileptics, see Chapter 4.8.2 . For further information on antiepileptics, see Chapter 2.10 .
Recommendation
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The choice of an antiepileptic for readjustment during breastfeeding is also determined primarily by effectiveness, i.e. according to the type of epilepsy.
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When possible, readjustment with an antiepileptic while breastfeeding should also take into consideration tolerance during a possible new pregnancy. This argues against therapy with valproic acid , in particular.
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A stable adjustment during pregnancy with whatever antiepileptic should not be uncritically changed or ended after birth.
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With good observation of the baby, monotherapy with one antiepileptic does not fundamentally argue against exclusive breastfeeding. However, antiepileptic therapy with barbiturates, clonazepam , ethosuximide or lamotrigine while breastfeeding should be critically evaluated in individual cases. This is especially the case for antiepileptic combination therapy, during which breastfeeding should be discouraged.
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If symptoms that cannot otherwise be explained, such as sedation, weak suckling and restlessness, reoccur, the concentration of the substance in the infant’s serum should be determined and an embryotoxicological center should be consulted so that a decision on weaning or supplementation with infant formula can be made. Particular care should be taken in the first 2 months of life, especially with premature and sick infants. Symptoms in the first few days of life are more likely attributable to adjustment disturbances due to prenatal exposure, rather than to medication in the milk.
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As with all CNS-effective medications, there is insufficient experience available on long-term effects of maternal maintenance therapy on breastfed children. However, there is, at yet, no serious indication that breastfeeding during antiepileptic therapy leads to developmental disorders in the child.
4.8.2
Individual antiepileptics
Carbamazepine
Carbamazepine has a half-life of 15–35 hours in both adults and newborns and 75% is protein bound. Studies on more than 50 milk samples showed M/P ratios of about 0.5. Including the metabolite carbamazepinepoxide , a relative infant dose of not more than 3–8% should be expected. In one case, however, with a maternal dose of only 250 mg daily, the relative infant dose of about 15% was determined ( ). Among breastfed children, serum concentrations between 0.5 and 1.5 μg/mL – but also in one case 4.7 μg/mL (therapeutic range 5–10 μg/mL) – were measured (survey in , , , ). Individual reports describe transient toxic liver changes in infants exposed prenatally and via the mother’s milk ( , ). One case report describes an infant with questionable seizures and a cyanotic attack, whose mother was taking fluoxetine and buspirone in addition to carbamazepine. Further development of the baby was normal through the end of the first year of life. The authors, quite rightly, hesitate to make a connection between the medication and the symptoms ( ). Another infant had feeding difficulties and was sedated during maternal anticonvulsive combination therapy with carbamazepine, phenytoin and barbiturates (survey in ). Further symptoms have not been published as yet. At 3 years of age, the IQs of the children breastfed when their mothers were taking carbamazepine were not lower than the IQs of children who were given infant formula because of their mothers’ carbamazepine treatment ( Section 4.8.1 , ). With carbamazepine monotherapy, the baby may be breastfed, with observation for possible side-effects.
Clonazepam
The half-life of clonazepam is 20–40 hours. Only 60% is protein-bound. In the serum of one child, 4.7 μg/L was measured. In the mother, it was between 15 and 30 μg/L ( ). The serum of a premature infant, whose mother had long-term therapy, was found to contain 13 μg/L. In another study, apnea occurred repeatedly in a premature baby. This was seen as being related to previous exposure in utero (survey in ). In a further case, a mother took 6 mg daily (plus 1,400 mg carbamazepine), and 20 μg/L were found in the serum of this baby. In the mother, it was 50 μg/L in her serum and 12 μg/L in her milk. The baby was described as “somewhat lazy at the breast” and tired (personal observation). Due to possible side-effects in the baby, breastfeeding with clonazepam is only conditionally acceptable.
Eslicarbazepine
There is insufficient experience available on eslicarbazepine while breastfeeding. Thus breastfeeding with eslicarbazepine is only conditionally acceptable.
Ethosuximide and mesuximide
Ethosuximide has a half-life of 55 hours. For the newborn, it is between 32 and 38 hours. Only a limited amount is protein-bound. The M/P ratio is 1. As studies on more than 10 mothers show, the infant can receive well over 50% of a child’s dose or the maternal weight-related dose. The concentration in the child’s serum can reach 10–40 mg/L (therapeutic range is 40–100 mg/L). Symptoms such as irritability, weak suck and sedation have been described in individual cases (survey in as well as ).
There is no data on mesuximide . Due to possible side-effects in the baby, breastfeeding is only conditionally acceptable with ethosuximide/mesuximide.
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