Lactating Mothers

Pharmacokinetics and pharmacodynamic alterations during lactation

  • Constant plasma concentrations are rare & drug levels are dependent on the half-life of the drug  (longer the half life = more likely to accumulate)
  • Substance must be absorbed in the mother via the GI tract
    • Only a fraction (~2%) of this dose will reach the infant
  • Infant dose (mg) = Mom’s dose (mg)  x  % absorbed by infant
    • Infant dose = Concentration in milk (mg/mL)  x  volume of milk (mL)
  • Various levels of absorption in infant based on pH, protein binding, fat, metabolism, metabolites
  • Drugs that Decrease milk supply:
    • Inhibit/block the effects of prolactin:  Dopaminergic agents (ergots, levodopa, B-6), estrogens, androgens, cannabis
    • Vasoconstrictors decrease blood flow to the breast
    • High dose diuretics or alcohol
    • Bromocriptine increases the risk of heart attacks, seizures & stroke.
  • Drugs that Increase milk supply:
    • Metoclopramide & neuroleptics inhibit dopamine secretion
      • Metoclopramide 10 mg PO TID for 7-14 days (taper down dose) has been used purposely to enhance lactation (most effective in the 1st months post partum)
    • Methyldopa acts as a false dopamine precursor
    • H2 antagonists (high dose) & tryptophan increase serotonin transmission
    • Fenugreek  (has been with the intent of increasing breast milk secretion)

Properties which make a medication likely to reach breast milk

  • Intracellular diffusion:  macrophages & lymphocytes
  • Transcellular diffusion:  lipid solubility & LMW
    • For diffusion into breast milk to occur the molecule should be LMW, lipid soluble, weakly basic (pH of milk is slightly basic), NOT highly protein bound (highly protein bound drugs will stay in the plasma)
  • Active transport into breast milk is relatively minimal

Benefits of maternal treatment verses the risk to the developing infant

  • Considerations:  dose & duration, infant maturity, quantity of milk consumed, experience with drug in infants, amt of oral absorption, potential LT effects, possible interference w/ lactation, non-dose related toxicity
  • Non-dose related toxicities:  allergic sensitization, effects on GI flora, hemolysis (G6PD deficiency), certain blood disorders
  • Diabetes
    • Insulin is safe to use in nursing mothers b/c it has a high MW
    • Tolbutamide is approved (chloropropamide is also similar)
    • Glipizide & glyburide excretion into breast milk is thought to be low but is unknown
  • Contraception
    • Use progestin-only products (ex. Micronor) in nursing mothers
      • Estrogen products may suppress lactation
    • IUDs are thought to be relatively safe but if systemic concentrations are reached, it will enter the milk
  • Antibiotics
    • Are generally safe due to their low levels in milk, but need to warn about non-dose related toxicities:  diarrhea, C. Diff, candida overgrowth
      • Many of the IV formulations aren’t orally bioavailable
    • Considered safe:  PCN, Cephalosporins, macrolides (zithromax), quinolones (Cipro, ofloxacin)
    • Caution:  chloramphenicol, sulfa drugs (during the 1st month of life), tetracyclines (after repeated use)
  • HTN:  wide variance between classes (some have the potential to reduce milk production), need to monitor for ADRs
    • BB:  propranolol & metoprolol are preferred
      • Caution:  atenolol, acebutolol
    • CCB:  nifedipine & nimodipine are preferred
    • ACE-I & diuretics should be used with caution (ACE-I:  developing kidneys; diuretics:  electrolyte imbalances)
    • Can use hydralazine
  • Analgesics:  IBU, APAP, codeine, hydrocodone, oxycodone, morphine are safe
    • Avoid NSAIDs with long half-lives (Naproxen & ketoprofen)
    • Ketorolac has minimal amounts transferred into milk but there’s a greater concern for the mother
    • Caution:  ASA (reye’s syndrome), COX-2 inhibitors
    • Avoid:  meperidine (metabolite w/ a long half-life)
  • Cough & cold meds:  antihistamines & decongestants both suppress lactation
    • Encourage increased fluid intake & potentially PSE & chlorpheniramine as alternatives
    • DXM is unlikely to accumulate in breast milk
    • Guaifenesine & saline NS are considered safe
    • Avoid long acting & multi-symptom drugs
  • Depression (moderate depression may not require treatment)
    • Caution:  Li, MAOIs, fluoxetine
    • Alternatives:  bupropion (wellbutrin), venlafaxine (active metabolite), escitalopram
    • TCAs can be used at low doses
    • SSRIs (paroxetine, sertraline) are pretty good
    • Order of preference:  sertraline > paroxetine > escitalopram > desvenlafaxine > venlafaxine
  • Benzos (LT use may cause accumulation in the infant & sedations)
    • Increased risk of SIDS
    • Try to only ones with short half-lives (ativan, xanax, midazolam) & try to use them briefly to minimize transfer to infant
  • GI & antisecretory drugs:  H2 blockers (famotidine, nizatidine) are generally considered safe, prilosec & prevacid also have a good track record
    • Don’t use reglan (metoclopramide) for greater than 2-4 weeks
  • Asthma:  most are safe b/c inhaled preps generally don’t have a lot of systemic absorption
    • Mast cell stabilizers (cromolyn, nedocromil) are the safest choice
    • Inhaled corticosteroids (fluticasone is preferred) are generally safe
    • Beta-2 agonist are generally the safest when inhaled (but terbutaline is safe as an oral med too)
    • Theophylline:  1% of dose gets into breast milk
    • LK inhibitors (monteulkast–singulair) have a low degree of transfer into breast milk & have poor oral bioavailability with food
  • Low amts of alcohol are ok during breastfeeding but advise against it generally & if they are going to drink try to spread the nursing out as much as possible
  • Smoking:  decreases duration of breastfeeding, milk volume, increases rates of SIDS, LRTIs, otitis media, colic
    • Nicotine itself is safer than smoking b/c it’s poorly absorbed  from human milk
      • Patches are safer than gum
    • Don’t breast feed if you are smoking a pack or more a day
  • Caffeine:  accumulates in infants due to greater half-life  (may cause irritability & poor sleeping patterns for kid)
  • Vaccines & seizure meds are ok
  • Caution use of antianxiety, antipsych, chloramphenicol, phenobarb, sulfa drugs
  • Most common herbal meds are probably safe
  • Avoid:  saw palmetto, tea, senna, coffee, ephedra

Strategies for optimizing maternal therapies while minimizing medication exposure to a nursing infant

  • Minimize exposure:  withhold the drug, delay therapy, choose drugs that will have low concentrations in breast milk (avoid combo agents if possible), alternative routes of admin, avoid times of peak concentrations, mother should admin drug prior to the infant’s longest sleep period, temporarily withhold nursing (pump), d/c breastfeeding

Sources available on the safety of medications administered while nursing

  • Drugs in Pregnancy & Lactation, Medication in Mother’s Milk, Toxnet, Lexi-Comp

Most common ADRs:  diarrhea in those on antibiotics, drowsiness in those on analgesics or sedatives, irritability in those on antihistamines
Drugs to avoid during lactation:

  • Immunosuppresives, antibeoplastics, drugs of abuse (including alcohol & nicotine), iodine, lithium, radiopharmaceuticals

Drugs of choice during lactation:

  • Analgesics:  APAP, IBU
  • Antidepressants:  Sertraline, TCAs
  • Antiepileptics:  phenytoin, carbamazepine, valproic acid
  • Antimicrobials:  pencillins, cephalosporins, aminoglycosides, macrolides
  • Cough & cold:  guaifenesin & dextromethorphan, increased fluids
  • Endocrine:  propylthiouracil (PTU), insulin, levothyroxine
  • Glucocorticoids:  Prednsione & prednisolone

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