Teaching in Twenty Medications and Breast Milk Barbara L. Philipp, MD, FAAP, FABM Professor of Pediatrics Boston University School of Medicine Boston Medical Center

Objectives: HANDOUT M2 Name 7 contraindications to breastfeeding Describe 3 pharmacokinetic factors that influence medications passing from mom to baby via breast milk List 2 reliable resources for information about medications and breast milk

Background - Mothers 90% of women are prescribed a medication in first week postpartum Mothers worry about effect of medication on nursing infant Leads to: non compliance, weaning, avoidance of breastfeeding 50% of mothers more reluctant to take a medication while nursing than during pregnancy

Background – Clinicians Frequently err erroneously on the side of caution Slide credit: M Bartick

Background – Clinicians And… Baby may not comply with “temporary” weaning Weaning, even temporarily, is traumatic Need to balance short term med concerns with long term breastfeeding benefits

Seven contraindications to breastfeeding (AAP 2005) Mother HIV + (in USA) Use of illegal drugs by mother Certain medications Active, untreated TB in mother Galactosemia in baby Mother HTLV + Herpes on breast

A mother is taking the following medication or drug. She asks you, “Is it to breastfeed?” What is your advice? HANDOUT M1 Cocaine Methadone Glass of wine Heparin Phenytoin (Dilantin) Lithium Magnesium sulfate TMP-SMZ (Bactrim) Tetracycline

How to decide if a medication or drug is ok? Pharmacokinetic factors Factors which govern drug transfer across membranes into breast milk as well as the metabolism of the drug in mother and infant

Pharmacokinetic factors 1.Passive diffusion 2.Molecular weight 3.Protein binding 4.Lipid solubility 5.Half life 6.Oral bioavailability

Passive diffusion Drugs move in and out of breast milk High to low With time direction may shift Example: alcohol

Molecular weight High molecular weight limits movement into breast milk MW >500 daltons does not enter breast milk

Molecular weight: examples Insulin: MW > 6,000 daltons Heparin: MW 40,000 daltons Ethanol: MW 200

Protein binding Medications circulate in maternal circulation bound or unbound to albumin Only unbound drug gets into maternal milk Definition of good protein binding = > 90%

Protein binding High protein binding Propranolol 90% L2 Diazepam 99% L3 Low protein binding Lithium 0% L3

Lipid solubility Drugs that are very lipid soluble penetrate into breast milk in higher concentration Drugs that are active in the CNS are drugs with high lipid solubility

Half life Short half life drugs Alcohol 24 min Keflex 50 min Ibuprofen 120 min General anesthesia Long half life drugs Prozac 216 hours

Oral bioavailability Amount of drug that is absorbed from the gut into the blood stream

Oral bioavailability Drug Maternal GI Tract Maternal Plasma Breast Milk Infant GI Tract Infant Plasma

Oral bioavailability Low bioavailability may be due to –Reduced absorption in GI tract –Poor GI stability due to acidity –High first-pass uptake by liver

Poor oral bioavailability Gentamycin –<1% oral bioavailability Insulin (destroyed in gut) –0% oral bioavailability Heparin (destroyed in gut)

Summary Drugs transfer into human milk if they: Attain high conc in maternal plasma Are small enough Are non-protein bound Are highly lipid soluble Then once in breast milk: Are affected by oral bioavailability in baby’s gut

In general, baby gets <1% of maternal dose of drug

Resources BAD Very Very Very Bad Physician’s Desk Reference (PDR) Major concern is legal risk

Resources OK AAP Statement Committee on Drugs. The transfer of drugs and other chemicals in human milk. Pediatrics 2001;108(3):

Resources THE BEST Medications and Mothers’ Milk Thomas Hale, Ph.D.

Medications and Mothers’ Milk Lactation Risk Category L1 Safest L2Safer L3Moderately safe L4Possibly hazardous L5Contraindicated

Resources THE BEST LactMed.com

What’s your advice? Cocaine No: Hale L5, drug of abuse contraindicated by AAP Methadone Yes: Hale L3, (if HIV neg, no illegal drugs) Alcohol (glass of wine) Yes: Hale L3, but common sense, moderation, peak levels

What’s your advice? Heparin Yes: Hale L1 –MW 30,000 daltons, oral bio 0% Phenytoin (Dilantin) Yes: Hale L2, AAP ok Lithium Used to be No: Hale L5 Now Yes: Hale L3 with close observation

What’s your advice? Magnesium sulfate Yes: Hale L1 TMP-SMZ (Bactrim) Yes: Hale L3, AAP ok Tetracycline Yes: Hale L2, AAP ok – binds to calcium in the milk (<3 weeks use)

Take Home Points Don’t guess Use Medication and Mothers’ Milk ( Use LactMed (or toxnet)

References Hale, Thomas. Medications and Mothers’ Milk, 14 th ed. Amarillo, TX: Pharmasoft, 2010 – LactMed on ToxNet –Massbfc.org has link to AAP document and LactMed