Drugs in Lactation Flashcards
True or false: the kinetics of transfer through placenta are similar to the transfer of drugs into human milk
false
they are different
True or false: a drug deemed unsafe in pregnancy is not necessarily unsafe for breastfeeding
true
What are the advantages of breastfeeding?
bonding –> physical/emotional
nutritional –> benefits from growth and development
protective –> GI infections, AOM, resp infections, SIDS
enhanced cognitive development
How long is exclusive breastfeeding recommended for?
6 months
What does CPhA recognize in regards to breastfeeding?
breastmilk is the normal and optimal food for infants that is a preventive health care measure
pharmacists are accessible and have a responsibility to promote breastfeeding
pharmacists are a prime source of information regarding drug exposure in breastfeeding
pharmacists need to respect parents choices for infant nutrition, whether feeding with breastmilk or substitutes
To what extent do drugs enter human milk of those drugs that reach systemic circulation?
almost all drugs which reach systemic circulation will enter human milk to some degree
-not likely at a level that is harmful to breastfed infant
-rarely produces clinical doses in the infant
When is a drug more likely to cause toxicity in an infant when the drug is administered through milk?
there is a chance that breastfeeding can lead to toxicity in infant if the drug enters the milk in pharmacologic quantities
What is required for maintenance of milk supply?
sufficient production
effective extraction
What are some medications that can cause insufficient milk production?
bromocriptine
COC (estrogen dose-related)
oral decongestants
antihistamines
nicotine
diuretics
What are the factors that can cause insufficient milk production?
previous breast surgery
-augmentation or reduction
poor initial feeding routines early postpartum
-infrequent feeding
-inadequate latch-on
-parent-infant seperation
-use of supplemental formulation
incomplete drainage
medications
What are the factors that can cause ineffective extraction?
poor technique
poor initial feeding routines early postpartum
-infrequent feeding
-inadequate latch-on
-parent-infant separation
abnormalities of nipple or infants mouth
blocked ducts
What are the two main considerations of drug use in lactation?
effect of drug exposure on infant via milk
effect of drug on milk production
What are the drug properties
that determine drug exposure in milk?
molecular weight: < 500-800 daltons
protein binding: low protein binding
Vd: small Vd
lipid solubility: highly lipid soluble (CNS-active drugs)
ionization: unionized
drug pKa: basic drugs
bioavailability: high
half-life: longer t1/2
What are the parent variables that can determine drug exposure in milk?
milk composition
concentration of drug
-dose, ADME, drug interactions
What are the infant variables that can determine drug exposure in milk?
milk consumption
-frequency of feeding, volume consumed
age
-GFR, hepatic metabolism (less robust until 6-12 months)
-preterm –> immature, permeable gut, lower capacity to metabolize and excrete drugs
True or false: dose of medications transferred to infant is generally subclinical with few exceptions
true
What is an important consideration with the parents medications and infants medications?
caution with interactions between medications being given to parent and medications being given to infant
What is the strength of data we have for safety of drugs in lactation?
similar limitations for drugs in pregnancy
-lactation an exclusion criteria for RCTs
-same defaults –> animal and observational data
What are the advantages we have with safety data of drugs in lactation?
direct observation
generally lower exposure via milk than placenta
What is the milk to plasma ratio?
concentration of drug in the milk compared to concentration of the drug in the plasma
- > 1 indicates that the drug concentrates in the milk
-does not indicate safety of the medication as it is only a ratio and not an absolute amount of drug
What is the relative infant dose?
a means of estimating infant exposure to drugs used in lactation
determined by concentration of the drug in the milk and volume of milk being consumed by infant divided by infants weight
What are the RIDs that are likely safe for short-term use?
< 10% (term infants)
< 1% (premature infants)
Generally speaking, we should choose drugs with a ____ RID.
select medications with LOWER RID may help maximize safety
What is the RID of most medications?
< 1%
What method is most accurate for estimating infant exposure?
infant plasma concentrations
-accounts for oral absorption/elimination effects
-limited availability
What are some strategies to limit infant exposure?
use only if necessary
decrease parental systemic exposure
-e.g. local application
avoid feeding at times of peak drug [ ] if possible
-once Css reached, timing not possible
What is “pump and dump”?
substitute with previously expressed milk or formula; current milk pumped and discarded
-duration determined by the elimination t1/2 of the med
-no true standard guidelines
What are the potential drug effects on milk production?
decreased production (insufficient supply to meet infants needs)
-before breastfeeding is established
-monitor certain cues in infant
increased production
-exploited therapeutically
What are some drugs that might reduce milk production?
antihistamines
decongestants
stimulants
diuretics
estrogen
nicotine
ergot alkaloids (bromocriptine)
What are some drugs that might increase milk production?
metoclopramide
domperidone
antipsychotics
What should be done if it is believed a mother has low milk production?
parents should be referred to their primary care provider and/or lactation consultant
What are galactagogues?
medications or other substances believed to augment maternal milk production
What are the most commonly prescribed galactagogues?
metoclopramide
domperidone
dopamine receptor antagonists, stimulates prolactin release
What is the general consensus on use of galactagogues?
routine use is not recommended
-limited evidence to support their efficacy
-potential safety concerns
-use with caution
What are the benefits of galactagogues?
benefit unproven
What is the RID of domperidone?
~ 0.1%
At what dose of domperidone are we concerned and why?
> 30-60 mg/day
QT prolongation
What are the adverse effects of domperidone in the mother?
dry mouth, HA, ND, SOB, palpitations, abdominal discomfort
QT
withdrawal
What are the adverse effects of domperidone in infants?
few reports
non-serious: diaper rash, hematuria, constipation
What is the RID of metoclopramide?
~ 4%
What is suggested with regard to stopping metoclopramide and why?
some studies suggested using a taper to avoid an abrupt drop in milk supply
How do metoclopramide and domperidone differ in distribution?
metoclopramide has BBB distribution
domperidone has poor distribution to BBB and breastmilk
What are the adverse effects of metoclopramide in the mother?
depression
TD with long term use
HA, ND, dry mouth, tiredness, breast discomfort, vertigo, restless legs, intestinal gas, hair loss, anxiety
What are the adverse effects of metoclopramide in the infant?
few reports
intestinal gas, intestinal discomfort
What is the bottom line regarding galactagogues?
most parents who receive instruction on BF technique and frequency are unlikely to derive much benefit from galactagogues
-galactagogues should not be considered before support, education, assessment of BF technique
optimal dose unknown
-studies low and short term
taper on d/c (unknown regimen)
monitor AEs
