Lactation (Andrews)

Learning Objectives 1. Describe the physiology and phases of milk production. 2. Identify key factors that influence drug transfer into breast milk . 3. Apply the concept of Relative Infant Dose (RID) and milk-to-plasma (M/P) ratio to assess medication safety. 4. Assess safety of drug exposure and evidence- based resources available. 5. Recommend specific pharmacotherapy in lactating patients.

Breasts is Best

Benefits for Infant and Mother

Infant (reduced risk of)

• Asthma, Obesity, Type 1 DM, Severe lower respiratory disease, AOM, SIDS, GI infections, Necrotizing enterocolitis in premature infants

Mother (lower risk of)

• HTN

• T2DM

• Ovarian cancer

• Breast cancer

Breastfeeding Recommendations

• Babies should be exclusively breastfed for 1st 6 months

• Continue breastfeeding with complementary foods for at 2 years

• Mothers should increase their diet by 300-400 kcal and continue prenatal vitamins and Omega-3 supplements

Mastitis

• What is it

• Common cause

• Treatment

• Inflammation of the breast that occurs in 3-20% of lactating women

• Milk stasis most common cause

• Pharm: 10-14 days penicillanase resistant penicillins (oxacillin, dicloxacillin) & 1st gen cephalosporins

• Nonpharm:

  • heat prior to feeding with direct massage of the affected areas toward nipple during feeding

  • Cold compress after feeding to decrease pain and edema

Lactation Pathophysiology

2 things happening at once

• Hypothalamus releases PRH → Anterior pituitary releases Prolactin → simulates milk production in mammary glands

• Hypothalamus → Posterior pituitary → Oxytocin (milk ejection)

PRH is prolactin-releasing hormone

Phases of Breastmilk

• Phase 1: Colostrum (immune-rich)

  • Thick milk after birth, rich in nutrients and antibodies

  • “Liquid gold”

• Phase 2: Transitional milk

  • 2-5 days after delivery up until 2 weeks after

  • Bluish-white color

  • Changes to meet babies needs

• Phase 3: Mature milk

  • 10-15 days after birth

  • Amount of fat changes as baby is fed and empties each breast

Drug transfer into breast milk

More likely to pass

• Low molecular weight (~300)

• Non-ionized

• Non-protein bound

• Highly lipid soluble

• Weak bases

• High bioavailability

Milk-to-Plasma (M/P) Ratio

• Ratio of drug concentration in milk v plasma

• M/P > 1 → higher concentration in milk

• Limitations

  • M/P point ratio can severely under/over- estimate exposure

  • Milk level may lag plasma level

  • In general, not very useful because of difference in bioavailability and clearance of medications

• M/P AUC is a better estimate of exposure

Relative Infant Dose (RID)

RID (%) = (Infant dose mg/kg/day / Maternal dose mg/kg/day) x 100

• < 10% of maternal dose often considered to be safe

  • dose does not account for infant pharmacodynamics

Breastfeeding Safety

• Continue when mother has cold, flu, and majority of other infections

  • Not HIV

  • Not on ART of sustained viral suppression

Stepwise Approach to Minimizing Infant Exposure

• Withhold the drug if possible

• Delay therapy if possible

• Choose drugs that pass poorly into milk

• Choose drugs for which data are available regarding safety in infants and/or pharmacodynamics in breastfeeding

• Choosing an alternative route of administration

What should be done if unable to change medication

• Avoid nursing at times of peak concentration

• Administer drug before infants’ longest sleep period

• Administer med immediately after breastfeeding

• Use caution with preterm infants because of potentially more immature organ systems

• Temporarily withhold breastfeeding

• Collaborate with physicians to monitor infants and discuss risk/benefits with patient

• Discontinue nursing as a last resort

Antimicrobials in lactating patients

Compatible

• Penicillins

• Cephalosporins

• Macrolides

• Aminoglycosides

Avoid

• Fluoroquinolones

• Metronidazole

• Nitrofurantoin

Which Beta Blockers have the lowest transfer into milk

Which should be avoided

• Propranolol

• Metoprolol

• Labetalol

Avoid Acebutolol and Atenolol

Which CCBs have the lowest transfer into breast milk

• Diltiazem

• Nifedipine

• Verapamil

Which ACEi have been reviewed by the AAP as compatitible for first few weeks of life

• Captopril

• Enalapril

Which Antihistamine is preferred

Side effects?

Which antihistamine crosses into breast milk

• Loratadine is preferred antihistamine

• 1st gen antihistamine have anticholinergic properties

• Diphenhydramine crosses into breast milk

Which nasal decongestants is compatible

Pseudoephedrine considered compatible

• Chronic use not recommended

• Pay attention to milk supply

Which med decrease milk supply

• Diphenhydramine, Cetirizine

• Pseudoephedrine

• Anticholinergics

• Dopamine agonists

• Estrogen-containing contraceptives

Which analgesic is safe in lactation

Acetaminophen

NSAIDs in lactation

• Ibuprofen and Ketorolac considered compatible

• Long acting NSAID (Naproxen) only for short term therapy

• Aspirin in low doses acceptable (< 162 mg/day)

Opiates in lactation

• FDA discourages use

• Brief periods of certain opioids may be compatible with breastfeeding if necessary

• Avoid

  • Meperidine

  • Oxycodone

  • Hydrocode

  • Codeine

Which anticoagulant is compatible in breastfeeding

• Warfarin does not cross into milk

• Heparin, due to its molecular weight, does not cross into milk

Which medications are high risk

• Amphetamines

• Amiodarone

• Chemo agents

• Ergot alkaloids

• Lithium

• Metronidazole

• Phenobarbital

• Statins

What can mother’s do when drug concentrations are at the highest

“Pump and dump”

Vaccines in lactation

• Most vax are safe

• Smallpox and Yellow Fever are C/I in nonemergency situations

• Caution with HPV if infants are vulnerable to respiratory illnesses

How much caffeine can be consumed

No more than 200-300 mg/day

Alcohol counseling

• Ingest minimally while breastfeeding

• Refrain from nursing during ingestion and for 2 hours after a single serving of alcohol

  • Wait an additional 2 hours for each serving

Tobacco counseling

• Not C/I but should be discouraged due to health risks (SIDS)

• Nicotine replacement therapy is compatible with breastfeeding as long as dose is less than number of cigs normally smoked

• Short acting products are recommended

• Discouraged angents

  • Bupropion

  • Varenicline

Summary

• Breast is best for first 6 months

• Most drugs are safe

• Ideal characteristics of drug during lactation

  • Short t_1/2

  • High protein binding

  • Low oral bioavailability

  • High molecular weight

  • Low lipid solubility

• Use RID + clinical judgement

• Consider the risks and benefits to both the infant and mother