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Medications and mothers' milk Dr Tom Hale

Using Medications in Breastfeeding Mothers


Thomas W. Hale, Ph.D. Professor Department of Pediatrics Texas Tech University School of Medicine

Copyright T.W. Hale, 2012


Colostral Phase

Copyright T.W.Hale, 2012


Folie 3 w5

Secretory Alveolar epithelium Most cuboidal here. A myoepithelial cell is shown as well as numerous Plasma cells(arrows). Tom Hale; 04.04.2003

From Day 1 to Day 4 Postpartum



Sodium 134-146

Sodium 8-15

Chloride 95-108

Chloride 10-20 Lactose 180

Albumin 35-50 g/L

Milk Volumes during first week postpartum

Drug Entry into Human Milk Compartment  

Copyright T.W.Hale, 2012

Albumin 0.3 g/L

Purist form of Pharmacokinetics Depends on :  Molecular weight (cut off at 800 Daltons)  Protein Binding  Lipid solubility  Volume of Distribution  pKa


Pharmacokinetics and Drug Levels in Milk

Risk to Infant 

Depends on 3 major factors  Choice of Drug  Age of the infant  Premature…some risk  Older

infant…minimal risk

Volume of milk  Colostrum….minimal risk  Full

breastfeeding… some risk stage breastfeeding…minimal risk



Pharmacokinetics and Drug Levels in Milk 

Lipid Solubility  More lipid soluble, the higher drug levels in milk Plasma levels  The Higher, the more drug enters milk  The Lower, the less enters milk (fluticasone) Transport processes are poorly understood  At least 5 drugs are thought to be transported but 4 do not attain clinical levels  Ranitidine, Cimetidine, Iodine, Nitrofurantoin, Acyclovir

Copyright T.W.Hale, 2012

Size exclusion really matters Drugs > 800 daltons enter milk poorly  Drugs < 300 daltons enter milk easily Protein Binding:  Higher the binding the poorer the levels in milk pKa  Higher the pKa the more drug is trapped in milk. trapping”

Vd  Higher the Vd, the lower the levels in milk

Other Kinetic Factors 

Oral bioavailability  Drug exposure via milk depends on the bioavailability of the drug in the infant.  Morphine (26%)  Large

proteins unabsorbed (heparin, etanercept, etc)

 Sumatriptan (14%)  Domperidone (13%)  Tetracyclines (most

poorly absorbed in milk)

Stability in GI tract of infant is important  Proton pump inhibitors are unstable at low pH.


Simple Diffusion of Drugs into Human Milk

Drugs with Apparent Transporters (Influx Transporters)

Iodine Acyclovir Cimetidine Nucleus


Nitrofurantoin Ranitidine ???



Levels in the Plasma compartment determine levels in milk. If none present in plasma, none in milkâ&#x20AC;Ś Extracellular Proteins Transported


Protein Transporters

IgM, IgG (minimally) Prolactin Nucleus

IGF-1 ????


Plasma Cell

Copyright T.W.Hale, 2012



Birth Control Preparations  

Avoid estrogen-containing products Progestin-only mini pills preferred.  Progestin receptors not present in ‘lactating tissues’  If suppression occurs, you can stop immediately.  Lots of calls on Merena IUD ??? Depo-Provera  Some controversy about lowering production (early postnatally), but not proven.  Do not use early postpartum, use BCP first, then Depo

Viral Diseases Influenza

Infant exposed by onset of maternal symptoms

Hepatitis A

Safe to Breastfeed

Hepatitis B

Safe ONLY after HBIG and Vaccination

Hepatitis C



Depends on timing but is relatively low risk


Do not breastfeed in this country

Varicella Zoster


Lyme Disease

Unsafe until treatment initiated.

Herpes Simplex

Cover lesions, AAP approved.

West Nile Virus

In milk, but infants unaffected.

Epstein Barr

Don’t know, probably safe

Copyright T.W.Hale, 2012

Penicillins, Cephalosporins are generally safe

Erythromycin, Zithromax are safe except early postpartum.

Clindamycin: safe… RID = 0.8% - 1.8% Fluoroquinolones



Dicloxacillin, Flucloxacillin, Cloxacillin good for mastitis. Increase risk of hypertropic pyloric stenosis with erythromycin

Ciprofloxacin - use cautiously. Now AAP approved. Ofloxacin, Norfloxacin, Levofloxacin may be preferred.

Metronidazole  Levels moderate but are considered safe. Commonly used in neonates. All may induce changes in intestinal Flora…diarrhea, candida overgrowth.

Vaccinations MMR Yellow Fever Hepatitis B Hepatitis A DPT Flumist Influenza Lyme Vaccine Varicella Inactivated Polio

Safe Safer than getting disease Safe Safe Safe Probably safe Safe Safe Safe Safe

Gardasil (HPV)




Preferred Beta Blockers  Preferred: Metoprolol, Labetalol, Propranolol,  AVOID: Acebutolol, Atenolol (poor choice) Preferred Calcium Channel blockers  Nifedipine, Nimodipine, Verapamil, Nitrendipine Preferred ACE inhibitors  Avoid in very premature infants  Captopril, Enalapril, Benazepril are preferred in breastfeeding mothers. Aldomet, hydralazine are fine.


Hydrocodone, morphine are generally safe in breastfeeding mothers. Fentanyl milk levels are low. Ibuprofen, Ketorolac, and acetaminophen are Ok Naproxen is not preferred but can be used briefly. Meperidine is poor choice due to neonatal sedation, neurobehavioral delay. Buprenorphine is a potent, long-acting narcotic agonist and antagonist. RID = 1.9%

Radiocontrast Agents and Milk Concentrations

Vitamin D    

Vitamin D levels in milk are low Infants need supplementation but its being resisted by this field. Vitamin D doses need re-evaluated in our population. Newborns need 400 IU/day



Milk (Cmax)




6.5 g

3.09 umol/L

Dose = 0.023%



0.77 g/kg

35 mg/L

Absorption Nil;

< 0.1%

Iopanoic Acid

2.77 g

20.8 mg

0.08% of maternal dose



5.06 g

32.9 mg/L

0.02% of maternal dose



580 mg


0.3% of maternal dose


* Gadolinium ionâ&#x20AC;Ś.not iodinated.

Copyright T.W.Hale, 2012


Half-lives of Radioisotopes Radioisotope

Oral Sodium or Potassium 131I



2.75 Days


3.05 Days

Ga Ga--67

3.26 Days


Ga Ga--67

78.3 Hours


8.02 Days

Xe Xe--133

5.24 Days


2.80 Days

Rapidly absorbed from GI tract Distributed to extracellular body water Largely trapped in thyroid Excreted by kidneys:



27.7 Days


60.1 Days

Sr Sr--89

50.5 Days


6.02 Hours


13.2 Hours

Sm Sm--153

47.0 Hours


30% of dose has T1/2 of 0.3 days 60% of dose has T1/2 of 7.61 days

Concentration in Breasts

Effect of Drugs on Milk Production

Copyright T.W.Hale, 2012



Prolactin Surge in Lactation

Prolactin is a 199 amino acid peptide hormone secreted by pituitary lactotropes 23,000 daltons Promotes:  alveolar survival  maintenance of tight junctions  protein and lactose synthesis  probably many more functions.

Drugs that Stimulate Prolactin          

Metoclopramide(Reglan) Domperidone(Motilium) (not in USA) Amitriptyline(Elavil) Androgens Sulpiride Chlorpromazine(Thorazine) Cimetidine (Tagamet) Fluphenazine Haloperidol(Haldol) MAO inhibitors(Nardil, Parnate)

Copyright T.W.Hale, 2012


Domperidone (Motilium) 



Peripheral dopamine antagonist Unlike Reglan, it does not enter the brain compartment and it has few CNS effects such as depression. Following 10 mg three times dailyâ&#x20AC;Ś the average concentration in milk was 2.6 ng/mL. Hofmeyr. Brit. J. Obs. and Gyn. 92:141-144, 1985.


Side Effect Profile        

Milk levels are very low. Gastric cramping Dry mouth Skin rash, pruritus Headache Abdominal Cramps, diarrhea NO CNS depression !!!! Prolonged QT interval, but rare.

Copyright T.W.Hale, 2012

Recommended Dose = 10-20 mg TID Available from compounding Pharmacies in USA or New Zealand.

My Suggestion re Domperidone  


Do not use in patients that are prone to arrhythmias. Do not be surprised if you rarely find a patient that has a prolonged QT interval when placed on higher doses of Domperidone. Avoid doses of domperidone higher than 10-20 mg TID. There is no good evidence that it works any better. Slow withdrawal apparently do not reduced milk production.


Summary-Dopamine Blockers

Drugs that inhibit lactation 

Strong Inhibitors  Some Ergot alkaloids (DHE45, Cafergot, etc)  Cabergoline (Dostinex)  Bromocriptine (Parlodel) Weak Inhibitors  Ergonovine  Pseudoephedrine (late stage lactation) (??)  Estrogens/Progestins  Bupropion (Zyban) (???)


Metoclopramide dramatically stimulates PRL and milk production in some mothers.  Depression, extrapyramidal jerks, facial tremors, tardive dyskinesia may result. Domperidone largely devoid of CNS effects but can cause GI symptoms. Suggest you avoid pseudoephedrine in later stage lactation. Be careful with progestins. Start with progestin-mini pill first.

Medications to Avoid  


Drugs of abuse Ergot alkaloids  Migraine preps  Ergotamine  Cabergoline Pseudoephedrine Anti-cancer drugs


Radioactive drugs  Discontinue briefly Radioactive I-131  Do not use. Chronic use of sedatives Estrogens Progesterone within 48 hours of birth.

Some Suggestions 

Always evaluate stage of lactation.  Premature…higher risk  First 4 days, low milk volume…..low risk  Late stage…low milk volume….low risk Calculate and use the Relative Infant Dose. If less than 10% then it is probably safe.


Copyright T.W.Hale, 2012

Infant dose (milk) ( mg/kg/day) Maternal dose (mg/kg/day)


Medications and mothers' milk  
Medications and mothers' milk  

Medications and mothers' milk at 7th International Breastfeeding and Lactation Symposium