Continuing drug therapy while breastfeeding: Part 2. Common misconceptions of physicians

Gideon Koren, MD, FRCPC; Myla Moretti, MSC; Shinya Ito, MD

May, 1999

Many women need drug therapy during the postpartum period to treat chronic or acute medical conditions. Mothers are naturally concerned about the potential risk to their suckling infants from drugs introduced through milk. Hence, it is crucial to identify methods that accurately define the safety or risk of such exposures, because every year scores of new drugs are introduced to the market.

For many years, the ratio between drug concentrations in maternal milk (m) and plasma (p) was used to estimate how much was getting through to a baby. The higher the m/p ratio, the higher concentrations were available to a baby, people assumed. This approach, however, was too simplistic from a pharmacokinetic viewpoint, because a drug's clearance rate from a baby's body is as important as the amount of drug offered to the baby.

Several years ago the Motherisk team developed a new concept, the Exposure index (EI), which incorporated both the m/p ratio and the clearence rate of the drug.¹ The formula is:
EI = 100 x m/p ratio
clearance (mL/kg/min)

The EI, in simple terms, is the percentage of maternal dose per kg available to the baby. This equation implies that, even if a drug appears at higher concentrations in milk than in maternal plasma, the clearance rate of the drug will define its safety. Experimental data show that this new concept better estimates the risk to the baby than the old m/p ratio.¹

In the case of lithium, which has a high m/p ratio, the EI is unsafely high in many infants, but, due to individual (faster) renal clearance rates, is quite low in many others. In several recent cases, we allowed women receiving lithium, who attended Motherisk, to breastfeed provided lithium levels were measured in breastmilk or neonatal blood. In other cases, such measurements proved the drug unsafe. We concluded that therapeutic drug monitoring could help ascertain whether breastfeeding was safe for women receiving drugs for which there are readily available methods of measurements.

Another relatively common misconception among physicians is in their approach to breastfeeding for women who drink alcohol or smoke cigarettes. While common sense dictates not drinking while breastfeeding, many women are chemically dependent and are unable to discontinue drinking. Advising them not to breastfeed ignores the increased morbidity and morality among formula-fed babies. Dr Jack Newman eloquently stated the case: "Those using drugs are also at the risk on many levels for increased infant morbidity and mortality. It is when the socioeconomic situation is the worst that breastfeeding has the greatest benefit."²

References

1. Ito S, Koren G. A novel index for expressing exposure of infants to drugs in breastmilk. Br J Clin Pharmacol 1994;38:99-102.
2. Newman J. Drugs in breastfeeding. Motherisk newsletter 1995;4:4.