Pharmacology and Toxicology in Lactation
The Pharmacology and Toxicology in Lactation domain tests risk assessment for maternal medications, substances, and galactagogues. The exam expects you to use pharmacokinetics and infant factors, not a simple list of forbidden drugs.
Principles
- Almost all drugs enter milk to some degree; the question is whether the infant dose is clinically important.
- Relative infant dose (RID) is the infant dose in mg/kg/day divided by the maternal dose in mg/kg/day, expressed as a percentage. An RID under 10% is generally low risk, but infant age, prematurity, and oral bioavailability matter.
- Favor drugs with short half-lives, high protein binding, low oral bioavailability, and established lactation data.
- Timing feeds before a dose or at a trough can reduce exposure for short half-life drugs, but is not needed for every medication.
- Monitor the infant for sedation, poor feeding, rash, or diarrhea; report concerns.
Specific agents
- Acetaminophen and ibuprofen are preferred analgesics. Avoid codeine and tramadol because CYP2D6 ultrarapid metabolizers convert codeine to morphine and can cause infant respiratory depression.
- Sertraline is often preferred among SSRIs because of low milk transfer and extensive data; fluoxetine has a long half-life and active metabolite.
- Penicillins, cephalosporins, and macrolides are generally compatible. Levothyroxine is compatible; methimazole is generally preferred over propylthiouracil for breastfeeding when appropriate.
- Progestin-only contraception is preferred when estrogen could reduce supply.
- Galactagogues such as domperidone, metoclopramide, and fenugreek have limited evidence and adverse effects; domperidone carries QT-prolongation risk.
- Alcohol: no safe amount is established. If a mother drinks one standard drink, waiting about two hours is reasonable; pumping and dumping does not speed elimination.
- Cannabis should be avoided because THC accumulates in fat and may affect neurodevelopment. Caffeine up to about 300 mg/day is generally acceptable.
- Most iodinated and gadolinium contrast agents, ultrasound, and plain radiography are compatible with breastfeeding.
Worked example
A breastfeeding mother of a 1-week-old asks for codeine after a perineal repair. The reasoning: codeine is a prodrug of morphine, and genetic variation in CYP2D6 can produce dangerously high morphine levels. A newborn has reduced clearance and higher risk of apnea and sedation. The safer plan is scheduled acetaminophen and ibuprofen; if an opioid is truly needed, use the lowest effective dose for the shortest time with infant monitoring.
Traps that cost marks
- Assuming all drugs enter milk and are therefore contraindicated.
- Treating an RID above 10% as an automatic stop signal.
- Recommending pump and dump for alcohol; it does not accelerate clearance.
- Calling herbal galactagogues risk-free.
- Relying on the milk-to-plasma ratio alone.