1. Drug Transfer Into Breast Milk and Interpretation of Data Lawrence J. Lesko Office of Clinical Pharmacology and Biopharmaceutics Center for Drug Evaluation and Research Advisory Committee for Pharmaceutical Sciences Rockville, Maryland July 20, 2001

2. Virgin of the Green Cushion Paris Stamp Havana Statue Madrid HHS Report United States

3. Demographics: 1998 61 million –number of women between 15-44 yrs of age 4 million –number of newborn infants 65% –fraction of infants who breastfeed 2.6 million –number of potential recipients of unwanted drug “residues”

4. Breast Milk or Formula: Making the Right Choice for Your Baby “Human milk is made for human infants. It meets all their specific needs.” - FDA Consumer, Sept 1998 Regulated by FDA No FDA Guidance

5. Medications in Breast-Feeding Mothers Benefits of Medication for Mother Risks of Medication to Infant Sources of Information: internet resources, 1:1 consultations, periodicals

6. http://www.perinatology.com Acyclovirexcretion into milk is concentrated Albuterolexcretion into milk is negligible Aminoglycosidesmost excreted into milk Amitriptylineexcreted into milk but effects on infant are unknown, may be of concern Caffeineexcreted into milk but acceptable when not used excessively All were rated “Compatible” with breast-feeding!

7. Medications in Breast-Feeding Mothers Benefits of Medication for Mother Risks of Medication to Infant Sources of Information: internet resources, 1:1 consultations, periodicals

8. “The dairy industry has a profound interest in producing high quality products free of antibiotic residues. Antibiotic residues in milk are a food safety concern to FDA’s Center for Veterinary Medicine.” - http://www.fda.gov/cvm “Antibiotics are widely used in veterinary practice for therapeutic purposes. Screening is often the first line of food safety monitoring for the presence of these drugs in milk.” - FDA Veterinarian, Sept/Oct, 1997

9. Purpose of Discussion Our responsibility as a regulatory agency –to identify and reduce the barriers related to medications which keep women from initiating or continuing to breastfeed their infants –major barrier is the paucity of reliable and comprehensive studies of drugs in breast milk well-designed breast-milk studies in NDA’s are rare

10. Purpose of Discussion (Cont.) To encourage improvements in the science of drug development –to provide data on the transfer of medications into breast milk and the potential risk to infants –to include more complete information in product labels related to breast milk –to empower woman, and their physicians, to make rational choices about benefits and risks

11. Dr. Arzu Selen - background, issues and questions Dr. Shinya Ito - assessing drug transfer into breast milk Dr. Pat McNamara - clinical methods and issues related drug transfer into milk