Infant drug exposure via breast milk

Abstract

More than half of women take medications during breastfeeding, predisposing their infants to medication exposure via breast milk. As a result, adverse drug reactions may emerge in the infant, although they are rarely reported. Disposition of maternal drugs in breast milk is described with several key parameters, which include relative infant dose (RID): infant drug intake via milk (weight‐ and time‐adjusted) expressed as a percentage of the similarly adjusted mother's dose. Most drugs show RID values of <10%, indicating that drug concentrations in infant serum do not reach a level known to be therapeutic in adults unless drug clearance is markedly lower than the adult level on a weight basis. RID is a function of milk‐to‐(maternal) plasma drug concentration ratio (MP ratio) and maternal drug clearance. Therefore, MP ratio between drugs must be interpreted not by itself but with maternal drug clearance of each drug. This is why some drugs such as phenobarbital show an MP ratio of <1 but an RID as high as 50–70%, while morphine shows an MP ratio of 2 but an RID in the range of 5%. Using RID, we interpreted case reports of infant adverse outcomes, and we observed cases with relatively low infant serum concentrations of drug, consistent with low RID, as well as those with near‐ or above‐adult therapeutic serum concentrations, with or without increased drug intake (i.e. high RID). It is important to consider both pharmacokinetic and pharmacodynamic factors in interpreting adverse outcomes in infants breastfed by a mother taking medications.

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

“…Overall, the milk/serum (M/S) ratio of 1 with relatively low clearance places the RID of levetiracetam in a relatively high 10-15% range in fully breastfed infants based on the clearancebased RID estimation. 18 Somewhat lower exposure was estimated by Tomson et al, who reported a daily infant dose of levetiracetam of 2.4 mg kg À1 , which corresponds to the RID value of 7.9%. 9 In that study, levetiracetam concentrations were measured in the infant's plasma and comprised 13% ($7.7-fold lower) of the drug concentration in the mother's plasma.…”

“…19 Estimations of infant exposure to drugs via breastmilk are important for the optimization of drug therapy in breastfeeding mothers, and specifically the RID value of 10%, which represents a particular arbitrary threshold, can be useful to estimate the risks of such exposure. 18 However, these estimations and thresholds do not replace the need to follow and investigate signs of potential toxicity in infants that are breastfed by drug-consuming mothers. In our study, somnolescence, which was probably related to levetiracetam exposure via breast milk, was reported in three infants.…”

Antihistamine use during breastfeeding with focus on breast milk transfer and safety in humans: A systematic literature review

“…The nine studies identified in our review covered analyses on nine antihistamines: cetirizine, chlorpheniramine, clemastine, ebastine, epinastine, loratadine, promethazine, terfenadine and triprolidine. The studies showed that the relative infant doses were below 5%, implying that the risk of pharmacological effects in breastfed infants is minimal 40 . However, in addition to the RID, other pharmacokinetic and pharmacodynamic factors (e.g.…”

Transfer of triptans into human breast milk and estimation of infant drug exposure through breastfeeding

“…An RID of 5%‐10% may be considered a threshold value in safety assessment 10,14‐16 . For most medications (with the exception of highly toxic agents), an RID below 10% would generally be considered compatible with breastfeeding 7 .…”