The Relative Infant Dose for Maternal Use of Drugs During Breastfeeding: Nuances in Derivation, Interpretation, and Application.

Medications used by lactating mothers appear in breast milk to varying extents and are ingested by the breastfed infant. The degree of exposure of infants to maternal medication is therefore a matter of concern. Key clinical considerations are the absolute exposure of the infant to the drug, the infant's age and capacity to metabolize the drug, and the possible effects of drug exposure in the infant. In this context, the relative infant dose (RID) is a useful construct that helps predict infant exposure without requiring infant blood sampling. By definition, the RID estimates the dose of drug that a breastfed infant ingests per day relative to the dose that the mother receives per day; dosing is standardized per kg body weight, and breast milk intake is standardized at 150 mL/kg/d. A drug with an RID that is <10% is conventionally considered to be compatible with breastfeeding; however, this interpretation is nuanced. This article explains the RID using a worked example. Clinically important issues in the derivation, interpretation, and application of the RID are discussed. Matters considered include how maternal weight and infant weight influence the estimated RID, the need to consider active metabolites, and study-related issues such as sample size and breast milk sampling. Special situations examined include intermittent drug dosing and rescue dosing, dosing with drugs that have long half-lives, use of prodrugs or long-acting injections, and use of drugs that may be problematic regardless of dose. Examples of the RID are provided for ketamine and its active metabolite norketamine, lurasidone, and viloxazine. Readers need to be aware that there is more to the RID than just the arbitrary 10% cutoff.