Medication Safety in Breastfeeding: Recommendations for Clinical Practice

Breastfeeding is universally accepted as the most desirable method of infant nutrition. However, it is sometimes discontinued prematurely due to concerns that medications taken by the mother may harm the child. The amount of a drug that passes into breast milk depends on its concentration in maternal serum and on the drug’s pharmacological properties. When prescribing medications to a breastfeeding mother, preference should always be given to those that pose the lowest possible risk to the infant. Ideally, dosing should be planned immediately before the infant’s longest sleep period. Physicians should rely on verified sources of information.

One of the most reliable and accessible resources is LactMed, a database maintained by the U.S. National Library of Medicine. This free online platform provides peer-reviewed, regularly updated information on the safety of numerous medications during breastfeeding.

Transfer of Drugs Into Breast Milk

Drugs enter breast milk primarily by diffusion from maternal serum, meaning the concentration in milk generally reflects the plasma concentration. Only a small number of drugs are actively transported into milk. Most drugs diffuse back into the maternal circulation as plasma levels decline.

Unlike pregnancy, where drugs cross the placenta, during breastfeeding the key factor is the infant’s ability to absorb the drug through the gastrointestinal tract. The amount of drug received depends on its concentration in milk, the volume of milk consumed, and the infant’s absorption capacity.

In the early postpartum period, drugs pass into milk more easily because of wider gaps between the alveolar cells of the mammary gland. However, since colostrum is produced in small quantities, infant exposure is limited. Topical medications are generally safer than oral ones, though products applied directly to the nipple can pose a risk if not removed before feeding.

The infant’s health also plays a role. Premature and ill newborns are more vulnerable because of immature metabolic and elimination pathways.

Strategies to reduce exposure include dosing immediately after breastfeeding and choosing drugs with poor oral absorption, low lipophilicity, and high protein binding, as such drugs are less likely to pass into milk.

Relative Infant Dose (RID)

The Relative Infant Dose (RID) estimates the amount of drug an infant receives through breast milk in relation to the maternal dose (mg/kg/day). It is calculated as:

RID (%) = (dose in milk mg/kg/day) / (maternal dose mg/kg/day) × 100

In clinical practice, an RID of less than 10% is generally considered safe, i.e., unlikely to cause clinically significant infant exposure. For most drugs, RID is well below 1%. If the RID exceeds 10%, a theoretical risk exists, requiring a careful benefit–risk assessment.

Treatment of Selected Conditions During Breastfeeding

Table 1. Recommendations for medication use during breastfeeding

Condition	Recommended drugs	Acceptable alternatives	Use with caution	Avoid
Allergic rhinitis	Cromolyn, decongestants, topical corticosteroids, saline	Loratadine	Pseudoephedrine	—
Analgesics	Paracetamol, ibuprofen, topical diclofenac	—	Opioids	Codeine, hydromorphone, meperidine, naproxen, oxycodone, tramadol
Antibiotics	Penicillins, cephalosporins	Macrolides, fluoroquinolones	Clindamycin, TMP/SMX, metronidazole, aminoglycosides, doxycycline	—
Anxiety	Lorazepam	—	Clonazepam	—
Asthma	Inhaled bronchodilators, inhaled corticosteroids, montelukast, prednisolone	Omalizumab	Theophylline	—
ADHD	Methylphenidate	Amphetamines	Atomoxetine, clonidine, guanfacine	—
Contraception	Non-hormonal methods, progestin-only contraceptives	—	Combined oral contraceptives	—
Depression	Paroxetine, sertraline	Desvenlafaxine, duloxetine, fluvoxamine, venlafaxine	Fluoxetine	—
Diabetes mellitus	Insulin, metformin, 2nd gen. sulfonylureas	—	DPP-4 inhibitors, GLP-1 agonists	—
Hypertension	ACE inhibitors, calcium channel blockers, diuretics	—	Beta-blockers, ARBs	—

Analgesics

Ibuprofen and paracetamol are first-line analgesics during breastfeeding, due to low concentrations in breast milk and proven safety in infants.

Long-term naproxen use is not recommended, as its long half-life is associated with risks of bleeding, anemia, and vomiting in infants. NSAIDs such as meloxicam, piroxicam, celecoxib, and etoricoxib are also not recommended due to limited safety data.

Local and topical anesthetics (e.g., lidocaine patches, infiltration anesthesia) are considered safe. If strong pain control requires oral opioids, hydrocodone or morphine are preferred due to better-known safety profiles. Breastfeeding should ideally take place before maternal dosing to minimize infant exposure. Since infants are sensitive to even small opioid doses, opioids should be used at the lowest effective dose, for the shortest possible time, and avoided in combination with other sedatives to reduce the risk of sedation or respiratory depression in the infant.

Antibiotics

Most commonly prescribed antibiotics are compatible with breastfeeding. Penicillins and cephalosporins are first-line agents.

However, all antibiotics may cause allergic reactions or diarrhea in infants due to changes in gut flora. Cases of hematochezia have been reported in infants exposed to IV clindamycin via breast milk.

TMP/SMX should be avoided in infants with hyperbilirubinemia, illness, prematurity, or stress due to the risk of kernicterus. TMP/SMX and nitrofurantoin should be avoided during the first month of life and in infants with G6PD deficiency due to the risk of hemolysis. Metronidazole exposure has been linked to candidiasis and diarrhea in infants. Calcium in breast milk may reduce absorption of fluoroquinolones and doxycycline. Fluoroquinolones have traditionally been avoided due to concerns about joint toxicity, though newer data suggest this risk is minimal.

Some antibiotics may alter milk taste, potentially reducing intake.

Mental Health and Breastfeeding

When psychiatric disorders occur during breastfeeding, the priority is effective maternal treatment, often with the same medications used during pregnancy. Most antidepressants are compatible with breastfeeding, but risk–benefit assessments are essential.

Stimulants (e.g., for ADHD) may reduce milk supply and should be used cautiously, with infant monitoring for irritability or poor weight gain.

Hypertension

Antihypertensive drugs are generally safe during breastfeeding.

Methyldopa, a first-line agent in pregnancy, may be continued during lactation. Calcium channel blockers transfer minimally into milk. Diuretics at antihypertensive doses do not affect lactation significantly. ACE inhibitors also have minimal transfer. ARBs are highly protein-bound and unlikely to transfer significantly, but safety data are lacking, so they are not recommended for neonates or preterm infants until further studies are available.

Beta-blockers vary in milk excretion; labetalol and metoprolol are considered safe with minimal milk transfer, but caution is required in premature infants.

Diabetes

Insulin, metformin, and second-generation sulfonylureas are preferred. Newer agents (SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors) lack sufficient safety data and are generally not recommended during breastfeeding.

Respiratory Disorders

Local and inhaled therapies (e.g., inhaled corticosteroids, bronchodilators, nasal sprays) have minimal systemic effects and are safe. Loratadine may be used for allergy symptoms.

Herbal Products

Herbal galactagogues (fenugreek, fennel, milk thistle) are commonly used, but evidence for efficacy is limited. Quality control is inconsistent, raising concerns about contamination or unknown ingredients.

Some herbs (coffee, yohimbine, sage, peppermint, parsley, chasteberry, jasmine) may harm the infant or reduce milk supply.

Information on herbal safety can be found in LactMed and e-Lactancia, though data are often limited due to a lack of clinical trials in breastfeeding women.

Contraception During Breastfeeding

In the first 4–6 weeks postpartum, non-hormonal methods (barrier methods, copper IUD) are preferred.

Combined oral contraceptives (estrogen + progestin) may reduce milk production and increase thrombosis risk, and are not recommended in early postpartum. Progestin-only methods (e.g., levonorgestrel IUD, etonogestrel implant) are safer and compatible with breastfeeding.

Reliable Sources of Information

Understanding pharmacokinetics and pharmacodynamics is critical for safe prescribing in breastfeeding. Clinicians should rely on up-to-date, evidence-based resources such as:

• LactMed (NIH, free database)

• e-Lactancia (Spanish/English, simple risk summaries)

• Medications and Mothers’ Milk (Thomas Hale – textbook, app, database)

• Drugs.com (updated patient information)

• MotherToBaby.org (educational fact sheets)

The U.S. Pregnancy and Lactation Labeling Rule (PLLR), implemented in 2014, requires clearer labeling on drug safety in pregnancy and breastfeeding, though many product labels remain outdated.

Reviews show that breastfeeding safety information varies in restrictiveness. Manufacturer labels are often conservative, while LactMed provides less restrictive, evidence-based assessments.

How to Minimize Infant Risk

General recommendations

• Avoid unnecessary medication use whenever possible.

• Drugs safe for infants are usually safe for breastfeeding mothers.

• Drugs safe in pregnancy are not automatically safe in breastfeeding.

• Use reliable sources to check drug safety in breast milk.

• Prefer local/topical therapy when possible (except on the nipple).

Drug selection

• Choose drugs with established safety data in breastfeeding.

• Favor drugs with low fat solubility, poor oral absorption, short half-life, and high protein binding.

Dosing

• For once-daily drugs, dose immediately before the infant’s longest sleep (usually after evening feeding).

• For multiple daily doses, feed the infant immediately before each dose.

• Use caution with drugs with long half-lives (e.g., diazepam). In such cases, assess carefully whether treatment is truly necessary.

Conclusion

Most medications are compatible with breastfeeding, especially with careful selection and individualized adjustments. Before advising mothers to interrupt breastfeeding or postpone treatment, clinicians should consult authoritative sources and weigh all options. Healthcare professionals play a crucial role in informing mothers and dispelling unfounded fears. Evidence-based decision-making ensures the safety and well-being of both mother and child.

References:

1. NIH. LactMed® Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/?term=lactmed

2. van den Oever HL, Versteegh FG, Thewessen EA, et al. Ciprofloxacin in preterm neonates: Case report and review of the literature. Eur J Pediatr. 1998;157:843–5.

3. Spencer JP, Thomas S, Trondsen Pawlowski RH. Medication Safety in Breastfeeding. Am Fam Physician. 2022 Dec;106(6):638–644. PMID: 36521462.

4. Hotham N, Hotham E. Drugs in breastfeeding. Aust Prescr. 2015;38:156–59. doi:10.18773/austprescr.2015.056