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 |
New generation antiepileptic drugs (AEDs) – pharmacokinetic and physicochemical characteristics and lactation risk categories
| AED | t0.5[h] | tmax [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) | 4.5 | 100 | 252 | 1.5-1.7 | 0.5 | 40 | 0.7 | 10.7 | L3 |
| LEV | 6–8 adults | 1.3 adults | 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 |
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 |
Old generation antiepileptic drugs (AEDs) – pharmacokinetic and physicochemical characteristics and lactation risk categories
| AED | t0.5[h] | tmax [h] | BA [%] | MW [g/mol] | RID [%] | M/P | PPB [%] | Vd [L/kg] | pKa | Hale’s (2019) lactation risk categories |
|---|---|---|---|---|---|---|---|---|---|---|
| VPA | 10–15 adults | 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 | 4 single dose | 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 | 4–16 adults (mean 8–9) | 100 | 236 | 3.8-5.9 | 0.69 | 70-80 | 08-1.8 | 7 | L2 |
| DZP | 20–50 (mean 43) adults | 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 | 0.5-0.6 | 7.2 | L4 |
Differences in composition of transitional and mature breast milk
| 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] | 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 |
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 | 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 |