Drugs in breastfeeding
Drugs in breastfeeding: transfer into milk and which drugs to avoid
Drugs in breastfeeding for FCPS Part 1: how drugs enter milk, ion trapping, infant absorption and clearance, and which drugs are safe or must be avoided. Covers lithium, amiodarone, codeine, cytotoxics, antibiotics for a breastfeeding mother and drugs that change milk supply.
How drugs enter milk
- Transfer is mainly passive diffusion of un-ionised, unbound drug from plasma across the alveolar epithelium, so milk levels follow maternal plasma levels and fall when plasma levels fall.
- Milk is slightly more acidic than plasma (about pH 7.1), so weak bases become ionised in milk and are trapped, giving a milk-to-plasma ratio above 1. Weak acids stay mostly in plasma.
- In the first few days, wide gaps between alveolar cells and small colostrum volume let more drug through, but the total dose is tiny.
| Favours entry into milk | Limits entry |
|---|---|
| Low molecular weight (lithium is a small ion) | Large molecules: heparin, LMWH, insulin |
| High lipid solubility | High protein binding (warfarin) |
| Low protein binding | Short half-life with dosing after feeds |
| Weak base | Weak acid |
| Long half-life (amiodarone) | Single dose |
- Relative infant dose: the dose the baby receives per kg as a percentage of the mother's dose per kg. Under about 10% is usually acceptable.
Infant factors
- The baby must still absorb the drug from its gut and then clear it. Neonates have immature glucuronidation, low CYP activity and a GFR about a third of adult values (per surface area), so preterm and very young babies accumulate drugs most.
- Polar drugs such as gentamicin enter milk a little but are barely absorbed from the infant gut; LMWH and insulin are large and destroyed orally. Both are compatible.
- Taking a once-daily dose just after a feed lets the plasma peak pass before the next feed; this helps less with long half-life drugs.
- Iodine is actively concentrated into milk by the breast's sodium–iodide symporter, so milk levels can exceed plasma.
Lithium: the model drug of concern
- Lithium is a small ion with no protein binding, so it enters milk freely; the infant's low GFR clears it slowly, and infant levels can reach a substantial fraction of the mother's.
- Signs of infant toxicity: lethargy, hypotonia, poor feeding, tremor, sometimes hypothyroidism.
- Dehydration or infection in the baby (vomiting, diarrhoea, fever) reduces renal clearance and raises lithium quickly. If a mother chooses to breastfeed, the baby needs close monitoring of feeding, hydration and, when concerned, serum lithium, renal and thyroid function.
Drugs to avoid or use with great caution
| Drug | Concern in the baby | Reason |
|---|---|---|
| Cytotoxic drugs (methotrexate, cyclophosphamide) | Marrow and immune suppression | Contraindicated |
| Radioactive iodine | Thyroid destruction | Stop breastfeeding |
| Amiodarone | Hypothyroidism | Rich in iodine, very long half-life |
| Heavy use of povidone-iodine | Hypothyroidism | Iodide concentrated in milk |
| Lithium | Lethargy, hypotonia, tremor | See above |
| Chloramphenicol | Marrow suppression, grey baby syndrome | Immature glucuronidation |
| Aspirin (analgesic doses) | Reye syndrome, platelet effects | Low-dose aspirin is usually continued |
| Codeine, tramadol | Sedation, apnoea, deaths reported | Ultra-rapid CYP2D6 metabolisers in the mother make excess morphine |
| Metronidazole 2 g single dose | High milk level | Pause feeding 12–24 hours; divided doses acceptable |
| Sulphonamides, nitrofurantoin | Jaundiced or G6PD-deficient newborn | Bilirubin displacement; haemolysis |
| Fluoroquinolones (ciprofloxacin) | Theoretical cartilage effects | Avoided when a safer alternative exists |
| Dopamine agonists, ergot alkaloids | Suppress lactation | Lower prolactin |
| Combined oestrogen pill | Reduces milk supply | Oestrogen opposes prolactin action |
| Benzodiazepines, phenobarbital (high doses) | Sedation, poor feeding | Slow neonatal clearance |
| Tetracyclines (long courses) | Teeth staining | Short courses acceptable; milk calcium limits absorption |
Choosing an antibiotic for a breastfeeding mother
- For a urinary tract infection, a beta-lactam such as cefalexin or amoxicillin–clavulanate gives very low infant exposure and is the safer alternative to ciprofloxacin.
- Nitrofurantoin is acceptable when the baby is healthy and G6PD status is normal, but is avoided if the newborn is jaundiced, preterm or of unknown G6PD status; trimethoprim–sulfamethoxazole is avoided in the jaundiced newborn for the same bilirubin reason.
- Any antibiotic may alter infant gut flora: watch for diarrhoea or oral thrush.
Drugs generally compatible with breastfeeding
- Analgesics: paracetamol and ibuprofen (short half-life, high protein binding).
- Antibiotics: penicillins, cephalosporins, erythromycin, gentamicin.
- Anticoagulants: heparin, LMWH and warfarin (highly protein bound).
- Antihypertensives: labetalol, nifedipine, enalapril; methyldopa is usually avoided after delivery because of depression.
- Diabetes: insulin and metformin. Thyroid: levothyroxine; propylthiouracil or carbimazole in modest doses.
- Antiepileptics: most are compatible; lamotrigine needs infant monitoring.
- Antidepressants: sertraline and paroxetine give low infant levels.
- Corticosteroids and inhaled drugs; aciclovir.
Pregnancy and breastfeeding compared
| Drug | Pregnancy | Breastfeeding |
|---|---|---|
| Warfarin | Avoid (crosses placenta, embryopathy) | Compatible (protein bound) |
| ACE inhibitor (enalapril) | Avoid in second and third trimesters | Compatible |
| Heparin, LMWH, insulin | Compatible (do not cross) | Compatible (do not enter or are not absorbed) |
| Lithium | Ebstein anomaly risk | Caution: enters freely |
| Carbimazole | Avoid in first trimester | Compatible in modest dose |
| Codeine | Use briefly | Avoid (CYP2D6 risk) |
Drugs that change milk supply
- Increase: dopamine antagonists such as domperidone and metoclopramide raise prolactin.
- Decrease: dopamine agonists (bromocriptine, cabergoline), oestrogens, pseudoephedrine.
Remember Ask two questions: does the drug get into the milk, and can the baby absorb and clear it?
Exam trap Drugs that do not cross the placenta because of size (heparin, LMWH, insulin) also do not enter milk in useful amounts.
Exam trap Warfarin is safe in breastfeeding despite being dangerous in pregnancy.
How FCPS asks about this
- Main mechanism of drug entry into milk: passive diffusion of un-ionised, unbound drug; weak bases are ion-trapped.
- Why lithium is a concern: enters milk freely (small, unbound) and infants clear it slowly; lethargy, hypotonia, tremor.
- Anticoagulant safe in breastfeeding: warfarin, heparin or LMWH.
- Antiarrhythmic causing infant hypothyroidism: amiodarone (iodine).
- Safer alternative to ciprofloxacin for UTI in a breastfeeding mother: cefalexin or another beta-lactam.
- Opioid analgesic to avoid while breastfeeding: codeine, because of ultra-rapid CYP2D6 metabolism.
Test yourself on this topic
5 of the 8 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A breastfeeding woman on a drug taken once daily is advised to take her dose immediately after a feed, just before the baby's longest sleep. Which principle underlies this advice?
Answer: Milk levels follow maternal plasma levels
Most drugs enter milk by passive diffusion, so milk concentration rises and falls with maternal plasma concentration. Taking the dose just after a feed means the peak plasma and milk level occurs during the long gap before the next feed, and by then levels have fallen. This reduces infant exposure without stopping breastfeeding.
Timing doses in breastfeeding
- Passive diffusion: milk follows plasma
- Dose just after a feed
- Peak passes before the next feed
- Lower infant exposure
Remember Feed first, then take the tablet.
Exam trap Timing helps little for drugs with very long half-lives, which have steady levels.
Why the other options are wrong
- Milk is made only during feeding Milk is secreted continuously between feeds.
- The drug is destroyed in stored milk Most drugs are stable in milk.
- Infant gut absorption is highest at night Infant absorption does not vary in this way.
- Prolactin blocks drug entry into milk Prolactin does not block drug transfer.
After a caesarean section, a breastfeeding woman needs six weeks of subcutaneous enoxaparin for thromboprophylaxis. She asks whether it will affect her baby. Why is the risk negligible?
Answer: It is a large molecule, inactive orally
Low molecular weight heparins have a molecular weight of about 4000 to 5000 Da and are highly charged, so very little passes into milk. Any that does is not absorbed from the infant's gut, as heparins are inactive when taken orally. Breastfeeding is therefore safe. Warfarin is also compatible because it is highly protein bound.
Heparin and breastfeeding
- LMWH: large, charged molecule
- Very little enters milk
- Not absorbed from the infant gut
- Safe to breastfeed
Remember Too big to pass, and useless by mouth.
Exam trap The same size property explains why heparin does not cross the placenta.
Why the other options are wrong
- It is destroyed by the alkaline pH of milk Milk is not alkaline, and this is not the mechanism.
- It is concentrated in the mother's liver Hepatic concentration is not the reason.
- It is bound to maternal red cells Heparins are not carried on red cells.
- It is excreted only in the mother's urine Excretion route does not explain safety.
A breastfeeding woman with puerperal sepsis is given intravenous gentamicin. Small amounts appear in her milk, but her baby's serum gentamicin stays undetectable. What is the main reason?
Answer: Polar drug, barely absorbed from the gut
Aminoglycosides are highly polar, water-soluble molecules that are poorly absorbed from the gastrointestinal tract, which is why they are given parenterally. Although small amounts pass into milk, the baby absorbs very little of the swallowed drug, so systemic levels stay negligible. Oral bioavailability in the infant is a key factor in deciding whether a drug in milk matters. Gut flora may still be altered.
Infant oral absorption
- Aminoglycosides are highly polar
- Poor gut absorption
- Infant levels stay negligible
- Infant oral bioavailability matters
Remember In milk is not the same as in the baby's blood.
Exam trap Watch for diarrhoea or thrush in the baby from altered gut flora.
Why the other options are wrong
- Gentamicin is destroyed by milk lipase Milk lipase does not destroy aminoglycosides.
- It is fully bound to proteins in milk Protein binding in milk is not the explanation.
- The infant kidney excretes it at once The neonatal kidney clears aminoglycosides slowly, not at once.
- Gentamicin cannot enter milk at all Small amounts do enter milk.
A breastfeeding mother of a 10-day-old baby develops typhoid fever, and a local practitioner suggests oral chloramphenicol. Why is chloramphenicol avoided in breastfeeding mothers of young infants?
Answer: Poor infant conjugation, marrow toxicity
Chloramphenicol is lipid soluble and passes into milk. Young infants have low hepatic glucuronyl transferase activity, so they conjugate and clear it poorly, allowing accumulation. It can cause dose-related marrow suppression and, in neonates, the grey baby syndrome (circulatory collapse), as well as rare idiosyncratic aplastic anaemia. Alternatives such as azithromycin or ceftriaxone are preferred.
Chloramphenicol in infancy
- Lipid soluble, enters milk
- Infant glucuronidation is immature
- Risk of marrow suppression
- Neonatal grey baby syndrome
Remember Immature conjugation makes chloramphenicol dangerous for babies.
Exam trap The same immaturity of glucuronidation explains neonatal jaundice.
Why the other options are wrong
- It is inactivated by proteins in milk Milk proteins do not inactivate it.
- It causes rickets by chelating calcium Calcium chelation is a tetracycline property.
- It suppresses the milk let-down reflex It does not affect the let-down reflex.
- It causes ototoxicity in the infant Ototoxicity is an aminoglycoside effect.
A breastfeeding mother of a 6-week-old asks which over-the-counter painkiller to avoid using regularly for her tension headaches. Which drug is the main concern, and why?
Answer: Aspirin: risk of Reye syndrome
Salicylate passes into milk, and regular maternal aspirin exposes the baby to a theoretical risk of Reye syndrome (acute encephalopathy with liver failure) and to impaired platelet function. Paracetamol and ibuprofen pass into milk only in small amounts and are the preferred analgesics. The ductus closes soon after birth, so ductal effects of NSAIDs matter only before delivery.
Analgesics in breastfeeding
- Preferred: paracetamol, ibuprofen
- Avoid regular aspirin
- Risk of Reye syndrome and platelet effects
- Avoid codeine (CYP2D6 variation)
Remember Breastfeeding headache: paracetamol or ibuprofen, not aspirin.
Exam trap Low-dose aspirin prescribed for a medical reason is usually continued; the concern is regular analgesic doses.
Why the other options are wrong
- Paracetamol: liver toxicity in the infant Paracetamol in usual doses is safe in breastfeeding.
- Ibuprofen: closure of the ductus The ductus is closed by 6 weeks; ductal effects matter in late pregnancy.
- Paracetamol: suppression of lactation Paracetamol does not reduce milk supply.
- Ibuprofen: kernicterus in the infant Ibuprofen at usual doses does not cause kernicterus.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Drugs in obstetrics and gynaecology, Drugs in breastfeeding
Read next
Drug dose pages
Doses, cautions and practical tips for drugs in this chapter.