Medicines and Breastfeeding Compatibility

Most medicines are compatible with breastfeeding because infants receive only a small fraction of the maternal dose through milk. Stopping breastfeeding is rarely needed, and it carries real costs: higher infant infection and mortality, loss of maternal protection from some cancers, and loss of a feeding route where formula is costly or unsafe. Compatibility depends on the drug, the dose, the duration, the age and health of the infant, and the feeding pattern.

Transfer into milk. Passage is higher for drugs with low molecular weight (under 300 Da), low protein binding, high lipid solubility, weak basic character (ion trapping in slightly acidic milk), and long half-life. Large, highly protein-bound, poorly absorbed or ionised drugs transfer little.

Relative infant dose. Infant dose (mg/kg daily) divided by maternal dose (mg/kg daily), expressed as a percentage. Under 10% is generally acceptable; under 1% is negligible. Exceptions need caution even under 10%: drugs with very toxic effects in infants, such as lithium, and drugs infants metabolise poorly.

Infant factors. Preterm infants, neonates under 2 months of age, and infants with reduced kidney, liver or enzyme function (including G6PD deficiency) are at highest risk. Infants over 6 months who take solid foods are at lower risk. Oral bioavailability in the infant matters: aminoglycosides, heparins, insulin and monoclonal antibodies are broken down or poorly absorbed in the infant gut.

Colostrum phase. In the first 3 to 4 days milk volume is small (30 to 60 mL daily), so total infant exposure is low even though mammary gland junctions are open.

Decision approach. Confirm the medicine is needed; choose the agent with the lowest infant exposure and the longest safety record; use the lowest effective dose; time the dose; monitor the infant; and document counselling.

Dose timing. Give once-daily medicines just after the longest feed, or at night. Give short half-life drugs just after a feed so that peak levels fall before the next feed. For single-dose exposures (for example imaging contrast), express and discard milk for a defined period.

Compatible, usual doses, no infant monitoring beyond routine.

• Analgesia: paracetamol 1 g orally every 4 to 6 hours (maximum 4 g daily); ibuprofen 400 mg every 6 to 8 hours (maximum 1.2 g daily); short-course morphine at the lowest dose.
• Antibiotics: penicillins, cephalosporins, macrolides, clindamycin, gentamicin, metronidazole at usual doses, nitrofurantoin (not in infants under 1 month or with G6PD deficiency).
• Antimalarials: artemether-lumefantrine, chloroquine, quinine, sulfadoxine-pyrimethamine (avoid if infant is under 1 month and jaundiced), atovaquone-proguanil if infant over 5 kg.
• Antihypertensives: enalapril 5 to 40 mg daily, captopril, nifedipine, amlodipine, labetalol, metoprolol, propranolol, methyldopa (watch for maternal depression).
• Diabetes: insulin, metformin, glibenclamide.
• Respiratory: salbutamol, inhaled corticosteroids, prednisolone (delay feeding 4 hours after doses over 40 mg), montelukast.
• Endocrine: levothyroxine, propylthiouracil up to 300 mg daily, carbimazole up to 20 mg daily.
• Gastrointestinal: omeprazole, antacids, laxatives (ispaghula, lactulose), ondansetron short course.
• Anticoagulants: heparin, low molecular weight heparin, warfarin.
• Psychiatric: sertraline and paroxetine (lowest infant levels), olanzapine, quetiapine.
• Antiepileptics: levetiracetam, carbamazepine, valproate (infant liver and platelet monitoring).
• Contraception: progestogen-only methods (implant, levonorgestrel intrauterine device, medroxyprogesterone acetate 150 mg IM every 12 weeks, desogestrel 75 micrograms daily), copper intrauterine device.
• Vaccines: all routine and travel vaccines (yellow fever vaccine only if exposure is unavoidable and infant is over 9 months).
• Antiretrovirals: tenofovir, lamivudine, emtricitabine, dolutegravir, efavirenz (breastfeeding is supported in HIV on suppressive therapy).
• Tuberculosis treatment: isoniazid (with pyridoxine for mother and infant), rifampicin, pyrazinamide, ethambutol. Give the infant isoniazid preventive therapy if the mother is infectious.

Use with caution and infant monitoring.

• Lithium: infant level, creatinine and TSH; avoid in preterm or dehydrated infants.
• Lamotrigine: infant levels may reach 30 to 50% of maternal; watch for rash, apnoea and poor feeding.
• Benzodiazepines: prefer lorazepam or oxazepam; avoid diazepam and long-acting agents; watch sedation.
• Opioids: morphine and oxycodone at lowest dose for under 3 days; watch sedation, poor feeding and respiratory rate.
• Gabapentin and pregabalin: watch sedation.
• Clozapine: agranulocytosis and sedation risk; infant blood counts.
• Sedating antihistamines (promethazine, chlorphenamine): watch sedation; reduce supply with prolonged use.
• Fluconazole single doses: acceptable; repeated high doses need infant review.
• Phenobarbital and primidone: infant sedation and feeding problems.
• Domperidone 10 mg 3 times daily for up to 7 days when used to raise supply: QT prolongation risk in the mother.
• Combined hormonal contraception: reduces supply; defer to 6 weeks or later.

Medicines that reduce milk supply. Oestrogen-containing contraceptives, bromocriptine, cabergoline, pseudoephedrine, high-dose diuretics and ergot alkaloids.

Avoid.

• Codeine and tramadol: ultra-rapid CYP2D6 metabolisers produce high morphine or O-desmethyltramadol levels; infant deaths reported.
• Amiodarone: iodine load and very long half-life.
• Cytotoxic chemotherapy, including methotrexate and cyclophosphamide, and mycophenolate.
• Radioactive iodine and most radiopharmaceuticals (interrupt breastfeeding for a set period set by the nuclear medicine service).
• Ergotamine: vomiting, diarrhoea and convulsions in the infant, plus suppressed lactation.
• High-dose aspirin (Reye syndrome); low-dose aspirin 75 mg is acceptable.
• Chloramphenicol: infant marrow suppression.
• Iodine-containing antiseptics applied to large areas.
• Illicit drugs, high alcohol intake, and nicotine replacement beyond short use (stop smoking first).

Alcohol and cannabis. Occasional alcohol (one unit of alcohol, then 2 hours before the next feed for each unit) is generally tolerated, but regular or heavy use impairs milk let-down and infant sleep; avoid cannabis and khat, which pass into milk and sedate or stimulate the infant.

Interactions. Rifampicin and enzyme-inducing antiepileptics reduce progestogen contraceptive efficacy; use a copper or levonorgestrel intrauterine device or medroxyprogesterone acetate. Combined use of several sedatives (opioid, benzodiazepine, antihistamine) in the mother increases infant sedation. Maternal CYP2D6 ultra-rapid metabolism or CYP2C19 variation changes codeine, tramadol and clopidogrel handling.

Special groups.

• Preterm infants and neonates under 2 months: choose drugs with relative infant dose under 2% and short half-life; avoid sedatives.
• Infants with jaundice or G6PD deficiency: avoid sulphonamides, nitrofurantoin, primaquine, dapsone and high-dose sulfasalazine in the mother.
• Maternal kidney or liver impairment: levels of renally or hepatically cleared drugs rise in milk; reduce the maternal dose.
• Maternal HIV: breastfeeding on suppressive antiretroviral therapy; exclusive breastfeeding for 6 months, continuing to 24 months in many East African programmes; infant prophylaxis (nevirapine with or without zidovudine) following the local schedule.
• Regional: unregulated herbal products, traditional galactagogues and over-the-counter analgesics are widely used in East Africa; ask about them. CYP2D6 ultra-rapid metaboliser frequency is high in some North-East African populations, strengthening the case against codeine and tramadol.

Infant monitoring. Feeding, weight gain, sleepiness, irritability, rash, jaundice, diarrhoea and oral thrush at each contact. Measure infant serum levels of lithium, lamotrigine, clozapine or phenobarbital if the infant is unwell or the drug has a narrow margin.

Maternal monitoring. Check supply (breast fullness, nappy output, infant weight) when starting drugs that may reduce milk volume.

Adjustment. Switch to a compatible alternative if the infant shows sedation, poor feeding or unusual irritability. Reduce the maternal dose, use a single bedtime dose, or pump and discard for the peak period when needed.

Stopping rules. Stop the medicine, or pause breastfeeding, if the infant is excessively sleepy, feeds poorly, has slow or irregular breathing, or shows signs of toxicity (for example lithium or opioid effects); seek urgent infant review. Resume breastfeeding once the maternal drug level is safe or the course is complete.

Referral and escalation. Discuss with a clinical pharmacist or medicines information service before cytotoxics, radiopharmaceuticals, immunosuppressants with little data, new antiepileptics, or when the infant is preterm, unwell or under 2 months. Refer infants with unexplained sedation, apnoea, seizures or poor weight gain after maternal drug exposure for urgent paediatric assessment.