1. Breastfeeding in the Drug-Dependent Woman
Paula K Schreck, MD, IBCLC, FABM
Mother Nurture Lactation College
Module 8: Lecture 3

2. Pharmacokinetic Factors
Plasma level of drug in the mother
Lipid solubility of the drug
pH of drug
Molecular size of drug
Protein binding of the drug in mother's plasma
Maternal T 1/2 of drug
There are many factors that LIMIT a drugs capacity to pass through the cell. These factors include…READ SLIDE

3. Transfer-Limiting Properties
Large molecular weight
Extreme pH
High protein binding
Water soluble
Low plasma levels
Short T 1/2

4. Infant Factors Gestational age Chronologic age
Infant’s medical condition
Oral bioavailability
First pass effect/ infant liver
Amount of breast milk ingested
Timing of dose and breastfeeding
There are infant factors that also effect the infant’s exposure to the drug as well. READ SLIDE

5. Relative Infant Dose RID = infant dose / maternal dose
Units = mg/kg/day
RID < 10% is favorable/considered acceptable
Baby gets <1% of maternal dose in most cases
Benchmarks have been developed that help us communicate the infant’s exposure. The RID is one of them..using a standard equation that plugs in the average weight of a mother and the average weight of an infant to estimate the infant’s “ Dose”.
A RID of less than 10% is considered acceptable by our field. Most the time, infants get less than that.

6. Ketorolac (Toradol) T 1/2 2.4 - 8.6 hours MW = 255
Protein binding = 99%
Oral bioavailability = >81%
pH = 3.5
(Class C in 2nd Trimester)
(Class D in 3rd Trimester)
Let’s look at some examples…

7. Ketorolac L2 T 1/2 2.4 - 8.6 hours MW = 255 M/P = 0.014 – 0.037
Protein binding = 99%
Oral bioavailability = >81%
pH = 3.5
M/P = – 0.037
Relative infant dose = <0.2%
Hale Classification: L2

9. Ethosuximide (Zarontin)
T 1/2 = hours
MW = 141
Protein binding = 0%
Oral bioavailability = complete
pH = 9.3
(Class C in pregnancy)

10. Ethosuximide (Zarontin)
T 1/2 = hours
MW = 141
Protein binding = 0%
Oral bioavailability = complete
pH = 9.3
M/P = 0.94
Relative infant dose = 31.4%
Hale Classification L4

11. Alternative L4 L2 Ethosuximide Phenytoin T 1/2 = 30-60 hours MW = 141
Protein binding = 0%
Oral bioavailability = complete
pH = 9.3
Hale Classification L4
T ½ 6-24 hours
MW = 252
Protein binding = 89%
Oral Bioavailability = 70%
pH = 8.3
Hale Classification L2

12. Drugs which Require the Cessation of Breastfeeding
Chemotheraputic agents (methotrexate)
Immunosuppressive agents (organ transplant)
Chloramphenicol ( aplastic anemia)
Ergotamines ( prolactin effect also)
Amiodarone ( cardiac arrythmia)
Doxepin ( TCA-metabolite)
Despite the protective nature of the milk plasma barrier.. There are some drugs that are JUST SIMPLY CONTRAINDIATED…

13. Drugs Which DO NOT Contraindicate Breastfeeding
Antibiotics
Analgesics (Avoid Demerol and Codeine)
Antidepressants (SSRI's, TCA's)
Anti-anxiety agents (Valium, Xanax)
Birth control
Most seizure medications

14. Key Factors Maternal Plasma levels Half Life Molecular Weight
Protein Binding
Infant Status

15. General Recommendations
Don't Guess
Use lactation specific resources
Examine pharmacology
Use Alternatives
If there is a delay in your decision---PUMP and SAVE

16. Alcohol: Lactopharmacology
T ½ = 0.24 minutes
MW = 46
M/P = 1.0
Protein Binding = 0%
Oral Bioavailability = 100% L3

17. Recommendations: Alcohol
Limit alcohol consumption to 8 ounces: 1 glass of wine or 2 beers
Drink after feeding ( 2-3 hour window)
If consumption greater than above, resume feeding when feeling neurologically normal
Heavy drinkers should not breastfeed

18. Marijuana: Lactopharmacology
T ½ = hours
M/P = 8
Protein Binding = 99.9%
Oral Bioavailability = complete
Let’s look at pharmacology….. The active ingredient is THC.
The M/P ratio of means that this active ingredient is present in human milk at levels up to 8 TIMES higher than maternal plasma and the metabolites are found in infant feces, meaning that is absorbed and metabolized.
It is rapidly distributed to the brain and adipose tissue and stored for weeks to months.
It’s long half life allows it to be detected in the urine for WEEKS, making it impossible to differentiate between an occasional vs a chronic user with a urine tox screen at birth.

19. Recommendations: Marijuana
Use of marijuana should be discouraged
Screen for poly-drug use
Not a contraindication for TERM BABY
Treatment program is a requirement
Mothers counseled on the risks associated

20. Methadone: Lactopharmacology
T ½ = hours
MW = 309
M/P = 0.68
Protein Binding = 89%
Oral Bioavailability = 50%
RID = 3%
pH = 8.6 L3

21. Recommendations: Methadone
Breastfeeding should be encouraged
Decreased NAS scores
Shorter hospital stays
Breastfeeding AT THE BREAST should be encouraged
The medical management of the NAS should be based on NAS scores while breastfeeding

22. Buprenorphine T ½ = 26 hours ( countered by naloxone) MW = 505
M/P = 0.68
Protein Binding = 96%
Oral Bioavailability = 15%
(almost 0 for naloxone)
RID = 1%
Similar to Methadone with RID even lower at <1%/ Recommendations are slimilar
So…If use of opioids has been determined a disorder, rather than short term use, in pregnancy, methadone or buprenorphine should be “strongly encouraged” along with bf

23. Hydrocodone T ½ = 3.8 hours MW = 299 pH: 8.9
Oral Bioavailability = Complete
RID = %%
Someppreparations also contain acetaminophen
Similar to codeine in action but slightly more potent
It too has a very low RID and is consistent with breastfeeding

24. Codeine T ½ = 2.9 hours MW = 299 pH: 8.2 Protein Binding: 7%
M/P ratio:
Oral Bioavailability = Complete
RID =8.1%
Mild analgesic
*About 7% is metabolized to a metabolite of Morphine which is much longer acting
*Reports of apnea and a handful of neonatal deaths
*Rapid Metabolizer: GYP206 = rapid conversion to morphine with increased narcotic effect
AVOID CODEINE in the NEONATAL PERIOD

25. Alprazolam ( Xanax) T ½ = 12-15 hours MW = 309 M/P 0.36 RID = 8.5%
( Valium T ½ = 43 hrs)
MW = 309
M/P 0.36
RID = 8.5%
PB = 80% L3
And finally, what about the benzodiazepenes:
Drugs such as Valium, Xanax
These drugs are commonly used for anxiety in pregnancy and in the perinatal period --- as an adjunct therapy for PPD. But they are also used as an adjunct therapy for treatment for narcotic withdrawal as well.
Even when used alone can cause a withdrawal syndrome with increased NAS scores
They do not contraindicate BF but one must be careful of increased sedation---with all of these agents.

26. Gateway Effect Polydrug use does occur
85% of mothers on opioids smoke cigarettes
12% use other opiates, Benzodiazaphenes, amphetamine, THC
Mothers are mostly honest ( 193/195)

27. ABM Supports Breastfeeding
Mother in treatment
No abuse for 90 days PTD
Negative drug screen at delivery
Consistent prenatal care
Stable dose of methadone or other treatment drug

28. ABM Discourages Breastfeeding
No prentatal care
Relapse of use of drugs within 30 days PTD
Not willing to enter treatment
Positive drug screen at delivery
Active drug use

29. ABM Urges Caution Relapse between 30-90 days prior to delivery
Concomitant use of psychotropic drugs
Late prenatal care
Remember these criteria are for TERM babies. The infants in the NICU and SCN are allowed to have a whole different set of rules

30. References and Contact Info
Paula Schreck, MD, IBCLC, FABM
Reece-Stremtan S, Marinelli K, et al. ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Use or Substance Use Disorder, Revised Breastfeeding Medicine. 2015;10(3):
An Initiative to Improve the Quality of Care of Infants With Neonatal Abstinence Syndrome
Matthew R. Grossman, Adam K. Berkwitt, Rachel R. Osborn, Yaqing Xu, Denise A. Esserman, Eugene D. Shapiro, Matthew J. Bizzarro
Pediatrics May 2017, e ; DOI: /peds
Rooming-In to Treat Neonatal Abstinence Syndrome: Improved Family-Centered Care at Lower Cost
Alison Volpe Holmes, Emily C. Atwood, Bonny Whalen, Johanna Beliveau, J. Dean Jarvis, John C. Matulis, Shawn L. Ralston
Pediatrics May 2016, e ; DOI: /peds