Teaching in TwentyMedications 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):776-789

Resources

THE BEST• Medications and

Mothers’ Milk• Thomas Hale, Ph.D.• www.ibreastfeeding.com

Medications and Mothers’ MilkLactation Risk Category

• L1 Safest

• L2 Safer

• L3 Moderately safe

• L4 Possibly hazardous

• L5 Contraindicated

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 (www.iBreastfeeding.com)

• Use LactMed (or toxnet)

References

• Hale, Thomas. Medications and Mothers’ Milk, 14th ed. Amarillo, TX: Pharmasoft, 2010– www.ibreastfeeding.com

• LactMed on ToxNet– Massbfc.org has link to AAP document and

LactMed