A position paper on breastfeeding by women with epilepsy – working group report

Component	Transitional milk	mature milk
Lactose [g/L]	20-30	67
Glucose [g/L]	0.2-1.0	0.2-0.3
Oligosaccharides [g/L]	22-24	12-14
Total proteins [g/L]	16	9
Lactoferrin [g/L]	3.53	1.94
slgA [g/L]	2.0	2.0
IgM [g/L]	0.12	0.2
IgG [g/L]	0.34	0.05
Total lipids [%]	2	3.5
Water soluble vitamins
Vitamin C [mg/L]		100
Thiamine [mcg/L]		200
Riboflavin [mcg/L]		400-600
Niacin[mg/L]	20	1.8-6.0
Folate [mcg/L]		80-140
Vitamin B12 [mcg/L]	0.5	0.5-1.0
Pantothenic acid [mg/L]	0.5	2.0-2.5
Biotin		5.0-9.0
Fat soluble vitamins
Retinol [mg/L]	2	0.3-0.6
Carotenoids [mg/L]	2	0.2-0.6
Vitamin K [mcg/L]	2-5	2-3
Vitamin D [mcg/L]		0.33
Vitamin E [mg/L]	8-12	3-8
minerals
Calcium [mg/L]	250	200-250
Phosphorus [mg/L]	120-160	129-140
Sodium [mg/L]	300-400	120-250
Potassium [mg/L]	600-700	400-550
Chloride [m/L]	600-800	400-450
Iron [mg/L]	0.5-1.0	0.3-0.9
Zinc [mg/L]	8-12	1-3
Copper[mg/L]	0.5-0.8	0.2-0.4
Manganese [mcg/L]	5-6	3
Selenium [mcg/L]	40	7-33

Table 2.

Lactation risk categories (Hale, 2019)

L1	Safest (compatible). Controlled studies in breastfeeding women have shown no negative effect on the child. Usually, non-absorbable drugs with low bioavailability
L2	Safer (probably compatible). No harmful effects found. Safety identified in small human studies. Breastfeeding is allowed
L3	Moderately safe (probably compatible). There are no controlled human studies. Some studies indicate a possible biological drug effect on the child. To be used, if the benefits outweigh the risks. This category covers all new, uncharted drugs
L4	Potentially hazardous. Documented risk for child or lactation. To be used if they are necessary for the mother and cannot be replaced by other drugs
L5	Hazardous. Significant harmful effects of the drug on the child, documented in human studies. Contraindicated in lactation

Table 3.

Old generation antiepileptic drugs (AEDs) – pharmacokinetic and physicochemical characteristics and lactation risk categories

AED	t_0.5[h]	t_max [h]	BA [%]	MW [g/mol]	RID [%]	M/P	PPB [%]	Vd [L/kg]	pKa	Hale’s (2019) lactation risk categories
VPA	10–15 adults 6–10 children	1-4	100	144	0.99-5.6	0.1-1.4 (mean 0.42)	80-95	0.1-0.4	4.8	L4
ESM	48–60 adults 16–58 children 32–38 newborns	4 single dose 3–7 multiple doses	100	141	31.4-73.5 (mean 62)	mean 0.94	<10	0.72	9.3	L4
PHT	7-42 (mean 22)	4–12	70-100	252	0.6-7.7	0.18-0.45	89	0.52-1.19	8.3	L2
CBZ	18–54 single dose 16–24 multiple dose	4–16 adults (mean 8–9) 4–6 children	100	236	3.8-5.9	0.69	70-80	08-1.8	7	L2
DZP	20–50 (mean 43) adults 20 children 80 newborns 30 prematures	1-2	100	285	0.88-7.14	0.2-2.7 (mean 0.5)	99	0.7-2.6	3.4	L3
PB	53–140	2-4	80-100	232	24	04-0.6	45–60 adults 3-43 newborns	0.5-0.6	7.2	L4

1 VPA – Valproic acid; CBZ – Carbamazepine; PHT – Phenytoin; DZP – Diazepam; PB – Phenobarbital; ESM – Ethosuximide

2 t_0,5 – half-life; t_max – time to maximum drug concentration; BA – bioavailability after oral administration; MW – molecular weight; RID – relative infant dose; M/P – milk to plasma ratio of a drug concentration; PPB – plasma protein binding; Vd – volume of distribution; pKa – the negative logarithm of the ionization constant of an acid

Table 4.

New generation antiepileptic drugs (AEDs) – pharmacokinetic and physicochemical characteristics and lactation risk categories

AED	t_0.5[h]	t_max [h]	BA [%]	MW [g/mol]	RID [%]	M/P	PPB [%]	Vd [L/kg]	pKa	Hale’s (2019) lactation risk categories
LTG	14–103 (mean 33 adults. monotherapy)	1–4 (mean 2.5)	98	256	9.2-18.27	0.057-1.47	55	09-1.3	5.7	L2
OXC	1.3–2.3 (OXC) 9 (MHD)	4.5	100	252	1.5-1.7	0.5	40	0.7	10.7	L3
LEV	6–8 adults 5–6 children	1.3 adults 0.5–1 children	100	170	3.4-7.8	1	<10	0.5-0.7	_	L2
LCM	13	1–4	100	250	NA	NA	<15	0.6	12.47	L3

1 LTG – Lamotrigine; OXC – Oxcarbazepine; LEV – Levetiracetam; LCM – Lacosamide

2 t_0,5 – half-life; t_max – time to maximum drug concentration; BA – bioavailability after oral administration; MW – molecular weight;

3 RID – relative infant dose; M/P – milk to plasma ratio of a drug concentration; PPB – plasma protein binding; Vd – volume of distribution;

4 pKa – the negative logarithm of the ionization constant of an acid; NA – no data

Table 5.

Clinical parameters assessing the safety of older generation AEDs during lactation (Davanzo et al., 2013; Hale, 2019)

AED	TID [mg/kg/day]	Oral therapeutic dose in infants [mg/kg/day]	RID [%]	Hale’s (2019) lactation risk categories	Drug safety
CBZ	0.7	10-20	3.8-5.9	L2	safe
CLN	0.002	0.1-0.2	2.8	L3	contraindicated
DZP	0.05	iv. 0.1-0.3 po. 0.5-1	0,88-7.14	L3	contraindicated
PHT	0.4	5-8	0.6-7.7	L2	safe
ESM	11.5	15-40	31.4-73.5	L4	contraindicated
PB	0.4	3-4	24	L4	moderately safe
PRM	0.9	12-20	8.4-8.6	L4	moderately safe
VPA	0.7	limited data in the neonatal period available	0.99-5.6	L3	safe

1 TID – theoretical infant dose; RID – relative infant dose

2 CBZ – Carbamazepine; CLN – Clonazepam; DZP – Diazepam; PHT – Phenytoin; ESM – Ethosuximide; PB – Phenobarbital; PRM – Primidone;

3 VPA – Valproic acid

Table 6.

Clinical parameters assessing the safety of new generation AEDs during lactation (Davanzo et al., 2013; Hale, 2019)

AED	TID [mg/kg/day]	Oral therapeutic dose in infants [mg/kg/day]	RID [%]	Hale’s (2019) lactation risk categories	Drug safety
GBP	1.7	10–15 (orly pediatric dose available)	1.3-6.6	L2	moderately safe
LTG	0.7	1–6 with valproic acid 5–15 with enzyme inducing AEDs	9.2	L3	moderately safe
LEV	3.9	5-10	3.4-7.8	L3	moderately safe
OXC	b.d.	27.7–50 (< 18 years)	1.5-1.7	L3	moderately safe
TGB	b.d.	<12 years limited data available	NA	L3	moderately safe
TPM	0.3	1–6 (< 2 years)	24.5	L3	moderately safe
VGB	0.1	25-50	1.5-2.7	L3	moderately safe
ZNS	1.9	5-8	28.9-36.8	L4	contraindicated

1 TID – theoretical infant dose; RID – relative infant dose

2 GBP – Gabapentin; LTG – Lamotrigine; LEV – Levetiracetam; OXC – Oxcarbazepine; TGB – Tiagabine; TPM – Topiramate; VGB – Vigabatrin;

3 ZNS – Zonisamide

References

Authors

Metrics

Articles in this issue

DOI: https://doi.org/10.21307/joepi-2020-005 | Journal eISSN: 2299-9728 (formerly 2300-0147) | Journal ISSN: 2300-0147

Journal RSS Feed

Language: English

Page range: 7 - 25

Submitted on: Jun 17, 2020

Accepted on: Jul 15, 2020

Published on: Jun 22, 2020

Published by: The Foundation of Epileptology

In partnership with: Paradigm Publishing Services

Publication frequency: 2 issues per year

Keywords:

women with epilepsy,

breastfeeding recommendations,

AEDs pharmacokinetics,

safety

Related subjects:

Medicine,

Clinical medicine,

Clinical medicine, other,

Neurology,

Pharmacology, toxicology,

Pharmacy,

Clinical pharmacy

© 2020 Joanna Jędrzejczak, Maria Wilińska, Ewa Kamińska, Ryszard Lauterbach, Ewa Helwich, Teresa Jackowska, Ewa Nagańska, Natalia Jacyna, Beata Majkowska-Zwolińska, published by The Foundation of Epileptology
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 28 (2020): Issue 1 (December 2020)