Opioids such as heroin, methadone, and morphine enter breast milk in quantities potentially sufficient to prolong the state of neonatal narcotic dependence if the drug was taken chronically by the mother during pregnancy. If conditions are well controlled and there is a good relationship between the mother and the physician, an infant could be breast-fed while the mother is taking methadone. She should not, however, stop taking the drug abruptly; the infant can be tapered off the methadone as the mother’s dose is tapered. The infant should be watched for signs of narcotic withdrawal. Although codeine has been believed to be safe, a case of neonatal death from opioid toxicity revealed that the mother was an ultra rapid metabolizer of cytochrome 2D6 substrates, producing substantially higher amounts of morphine. Hence, polymorphism in maternal drug metabolism may affect neonatal exposure and safety. A subsequent case-control study has shown that this situation is not rare. The FDA has published a warning to lactating mothers to exert extra caution while using painkillers containing codeine. More recent research has also shown that blood-brain barrier levels of P-glycoprotein are lower at birth, allowing more morphine to penetrate into the brain, than later in infancy and childhood. This can explain sedation in breast-fed neonates even when there is no genetic variability in CYP2D6.
Minimal use of alcohol by the mother has not been reported to harm nursing infants. Excessive amounts of alcohol, however, can produce alcohol effects in the infant. Nicotine concentrations in the breast milk of smoking mothers are low and do not produce effects in the infant. Very small amounts of caffeine are excreted in the breast milk of coffee-drinking mothers.
Lithium enters breast milk in concentrations equal to those in maternal serum. Clearance of this drug is almost completely dependent upon renal elimination, and women who are receiving lithium may expose the infant to relatively large amounts of the drug.
Radioactive substances such as iodinated 125I albumin and radioiodine can cause thyroid suppression in infants and may increase the risk of subsequent thyroid cancer as much as tenfold.
Breast-feeding is contraindicated after large doses and should be withheld for days to weeks after small doses. Similarly, breastfeeding should be avoided in mothers receiving cancer chemotherapy or being treated with cytotoxic or immunomodulating agents for collagen diseases such as lupus erythematosus or after organ transplantation.
Because of differences in pharmacokinetics in infants and children, simple proportionate reduction in the adult dose may not be adequate to determine a safe and effective pediatric dose. The most reliable pediatric dose information is usually that provided by the manufacturer in the package insert. However, such information is not available for the majority of products, even when studies have been published in the medical literature, reflecting the reluctance of manufacturers to label their products for children. Recently, the FDA has moved toward more explicit expectations that manufacturers test their new products in infants and children. Still, most drugs in the common formularies, eg, Physicians’ Desk Reference, are not specifically approved for children, in part because manufacturers often lack the economic incentive to evaluate drugs for use in the pediatric market.
Most drugs approved for use in children have recommended pediatric doses, generally stated as milligrams per kilogram or per pound. In the absence of explicit pediatric dose recommendations, an approximation can be made by any of several methods based on age, weight, or surface area. These rules are not precise and should not be used if the manufacturer provides a pediatric dose. When pediatric doses are calculated (either from one of the methods set forth below or from a manufacturer’s dose), the pediatric dose should never exceed the adult dose.
The current epidemic proportions of childhood obesity calls for a fresh and careful look at pediatric drug dosages. Studies in adults indicate that dosing based on per-kilogram body weight may constitute overdosing, because in obese subjects, drugs are distributed based on lean body weight.
Surface Area, Age, & Weight