Table 3.

Clinical relevant parameters for each antiepileptic drug and assessment of their lactation risk

Drug	TID†	Neonatal therapeutic oral dose	RID‡	Assessment of the lactation risk according to:
	(mg/kg/day)
			(%)
				Hale 2012§	LactMed 2013	Present study
		(mg/kg/day)
					(including adverse drug reactions)
Carbamazepine	0.7	10 - 20	3.8 - 5.9	L2	▪ CBZ levels are relatively high in breast milk	Safe
					▪ Breastfed infants have serum levels that are usually below the therapeutic range.
					▪ Side effects were rarely reported as sedation, decreased suckling, withdrawal reactions and 3 cases of liver dysfunction.
					▪ Infant should be monitored for jaundice, drowsiness, adequate weight gain, and developmental milestones especially in premature infants, exclusively breastfed and in combination with other antipsychotics.
Clonazepam	0.002	0.1 - 0.2	2.8	L3	▪ Monitor growth, sedation, developmental milestones, especially in preterm neonates, exclusively breastfed infants and if mother is receiving psychotropic drugs.	Contraindicated
					▪ Monitoring of serum concentration in breastfed infant, if excessive sedation occurs.
Diazepam	0.05	IV dose available:	7.1	L3	▪ Accumulates in maternal milk and serum of breastfed infant. Other agents are preferred, especially while nursing a newborn or preterm infant.	Contraindicated
		0.1- 0.3
		Oral dose
					▪ Single dose does not require delaying feeding.
		0.5 – 1 [76]
Ethosuximide	11.5	15 – 40	31.4-73.5	L4	▪ Monitor infant for drowsiness, adequate weight gain and psychomotor development.	Contraindicated
					▪ Measurement of an infant serum level might help rule out toxicity, if there is a concern.
Gabapentin	1.7	Only paediatric dose available:	1.3 - 6.6	L2	▪ Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.	Moderately safe
		10-15
Lamotrigine	0.7	1-6 with valproate, 5-15 with enzyme inducing AEDs	9.2	L3	▪ It is not necessary to discontinue breastfeeding, but any adverse effects such as apnoea, rash, drowsiness, decreased sucking are to be monitored and serum levels are to be measured.	Moderately safe
					▪ Monitoring of the platelet count may also be advisable.
Levetiracetam	3.9	5 - 10 [78]	3.4 - 7.8	L3	▪ Monitor infant for the appearance of sleepiness, increase appropriate weight, normal psychomotor development.	Moderately safe
Oxcarbazepine	NA	27.7 – 50	1.5-1.7	L3	▪ Monitor the infant for drowsiness and decreased feeding, and developmental milestones especially in the first 2 months of life.	Moderately safe
		(<18 years) [72]
Phenobarbital	0.4	3-4	24	L3	▪ The presence of phenobarbital in breast milk may mitigate possible neonatal abstinence.	Safe
					▪ Monitor the breastfed infant for the possible onset of drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants and antiepileptic polytherapy.
					▪ Measurement of the infant’s serum drug concentration might help rule out toxicity.
Phenytoin	0.4	5-8	0.6-7.7	L2	▪ The proportion ingested by infants is small and generally brings about no problems except in rare cases of idiosyncratic reactions.	Safe
Pregabalin	NA	5-14 [79]	NA	L3	▪ Compatible with breastfeeding.	Moderately Safe
					▪ An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Primidone	0.9	12-20	8.4-8.6	L3	▪ The presence of phenobarbital in breast milk may mitigate possible neonatal abstinence.
					▪ Monitor the breastfed infant for the possible onset of drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants and antiepileptic polytherapy.
						Safe
					▪ Measurement of the infant’s serum drug concentration might help rule out toxicity.
Tiagabine	NA	<12 years: limited data available.	NA	L3	▪ Monitor the infant for the onset of drowsiness, for adequate weight gain and for developmental milestones especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.	Moderately safe
					▪ Other drugs should be preferred especially while nursing a newborn or preterm infant.
Topiramate	0.3	1 - 6	24.5	L3	▪ Monitor the infant for the onset of diarrhea, drowsiness, increase appropriate weight and psychomotor development.	Moderately safe
		(<2 years) [80]
Valproate	0.7	Limited data available in the neonatal period.	1.4-1.7	L3	▪ Breastfed infants are at risk for hepatotoxicity.	Safe
					▪ Monitor the infant for unusual bleeding (a case of thrombocytopenia has been reported).
Vigabatrin	0.1	25-50	1.5 – 2.7	L3	▪ Until more data are available, vigabatrin should only be used with careful monitoring during breastfeeding.	Moderately safe
	S-enantiomer
Zonisamide	1.9	5 – 8	28.9 -36.8	L4	▪ Monitor infant for drowsiness, adequate weight gain and psychomotor development.	Contraindicated
					▪ Measurement of an infant serum level might help rule out toxicity if there is a concern.

^†TID theoretical infant dose.

^‡RID relative infant dose.

^§ Hale lactaction risk categories: L1: safe drugs at the highest level, L2: safe, L3: moderately safe; L4: possibly dangerous, L5: contraindicated. Present study risk categories: The moderately safe category has a less documented safety profile due to a short clinical experience and lack of studies. The moderately safe AEDs can be used, but the lowest dose of the drug should be chosen and the nursing infant should be clinically monitored and, when possible, his/her plasma level should be checked.

Data drawn from reference 1,41 except where otherwise specified. NA: indicates that no data are available.