Published: 10 June 2015
Amended: 3 February 2016

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Medicine Use in Lactation

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For a specific medicine, see the data sheet or consumer medicine information for information about use in lactation. You can also refer to the medicine monograph on the New Zealand Formulary website.

Prescriber Update 36(2): 22-25
June 2015

Medicines are often needed by women who are breastfeeding. However, there is often a lack of, or ambiguous, information about the safety of medicines transferred to the infant in breast milk. This has meant that in the past breastfeeding has been stopped unnecessarily or a different, potentially less appropriate treatment prescribed¹.

Although most medicines are excreted in breast milk to some degree, the amount is usually less than 10% of the maternal dose. Medicines excreted at less than 10% are considered compatible with breastfeeding. Therefore, with a few exceptions the majority of medicines may be used².

Almost all medicines pass into breast milk via passive diffusion. The amount available is dependent on a number of factors such as:^3,4,5

• oral bioavailability
• plasma half-life
• lipid solubility
• molecular weight or size
• ionisation
• percentage of maternal protein binding
• composition of the milk.

For example, breast milk is slightly more acidic than plasma (pH 7.1 compared with pH 7.4)⁵. Therefore, medicines with a higher pH (basic) such as β-blockers will diffuse into the milk more readily. The relatively acidic milk then changes the physicochemical structure of the medicine, shifting the equilibrium between the ionised and non-ionised forms to the ionised form. The ionised form is less able to diffuse back from the milk to the plasma, thereby becoming 'trapped' in the milk⁵.

In addition to being more acidic, breast milk contains more lipids and less protein than plasma. Because of breast milk lipophilicity, medicines with high lipid solubility are more likely to concentrate in the breast milk⁴.

Medicines with a high molecular weight (eg, insulin and heparin) do not readily transfer into breast milk as they are too large to cross mammary epithelium cell walls³. Active transport or dissolution in lipid membranes of cells is required, reducing the likelihood of these medicines passing into breast milk.

Highly maternally protein bound medicines are also less likely to pass into breast milk as the more bound a medicine is, the less efficiently it can cross cell membranes³.

As all medicines have a combination of these factors and milk composition changes with time, there is variability in medicine transfer into breast milk.

The safety of breastfeeding whilst taking medicines also depends on the age of the infant as drug metabolism and clearance is reduced in the neonate⁶.

An up-to-date database of medicine levels in breast milk and infant blood and possible adverse reactions in the nursing infant is available at LactMed (www.toxnet.nlm.nih.gov/newtoxnet/lactmed.htm). The World Health Organization (WHO) has also produced a classification guide for medicines use in breastfeeding based on the WHO list of essential drugs (www.who.int/maternal_child_adolescent/documents/55732/en/).

Medicines with inherent toxicity or those with high infant exposure and therefore potential for significant toxicity are contraindicated during breastfeeding, and include:⁴

• cytotoxic agents
• immunosuppressive agents
• amiodarone
• lithium
• ergotamine
• gold salts
• isotretinoin.

Radiopharmaceutical administration also requires temporary cessation of breastfeeding⁷.

There are a range of health issues that affect women who are breastfeeding. These most commonly include infection, depressive disorders, pain, contraception, low milk supply and atopic conditions¹. Table 1 provides information on the compatibility of medicines used in the treatment of these conditions with breastfeeding.

Table 1: Compatibility of commonly used medicines with breastfeeding^2,7,8

Condition	Treatment	Breastfeeding Recommendation	Additional Information
Infection	Antibiotics
	β-lactams (eg, amoxicillin)	Compatible	Gastrointestinal flora changes possible; monitor infant for diarrhoea, vomiting, thrush
	Macrolides (eg, erythromycin)	Compatible	Single dose of azithromycin considered safe
	Cephalosporins (eg, cephalexin)	Compatible	May also affect infant gut flora (third generation more likely)
	Fluoroquinolones (eg, ciprofloxacin)	Avoid if possible	Potential risk of arthropathies
	Trimethoprim	Compatible
	Nitrofurantoin	Compatible	Avoid nitrofurantoin if infant less than one month old or premature
	Metronidazole	Avoid if possible	If single 2 g metronidazole dose given, discontinue breastfeeding for 12 hours
	Antifungals
	Azoles (eg, fluconazole)	Compatible	If applying miconazole oral gel to nipples, apply after breastfeeding
	Nystatin	Compatible
	Antivirals
	Aciclovir	Compatible
Depressive disorders	Antidepressants
	SSRIs (eg, paroxetine)	Compatible	Paroxetine and sertraline preferred due to shorter half-lives
	TCAs (eg, amitriptyline)	Less preferred due to potential toxicity	Amitriptyline compatible in doses up to 150 mg/day
	Anxiolytics
	Benzodiazepines (eg, temazepam)	Compatible in a single dose; avoid repeated doses	Short-acting benzodiazepines preferred as accumulation may occur Monitor infant for drowsiness
Pain	Analgesics
	Paracetamol	Compatible	Paracetamol analgesic of choice
	NSAIDs (eg, ibuprofen)	Compatible	Avoid breastfeeding with long-term acetylsalicylic acid treatment
	Opiates (eg, codeine)	Compatible in occasional doses	Monitor infant for drowsiness, apnoea, bradycardia and cyanosis Use codeine with caution in rapid metabolisers
	Tramadol	Compatible
Contraception	Hormonal methods
	Progesterone	Compatible	See data sheet
	Oestrogen	Avoid if possible	May inhibit lactation
Allergies and hay fever	Antihistamines
	Sedating (eg, promethazine)	Probably compatible	Occasional use probably safe Monitor for sedation in mother and infant
	Non-sedating (eg, loratadine)	Compatible
	Topical
	Corticosteroids (eg, hydrocortisone)	Compatible	If applying to breasts apply after feeding
Asthma	β2- adrenergics (eg, salbutamol)	Compatible
	Corticosteroids (eg, budesonide)	Compatible
Other	Warfarinbr	Compatible
	Metformin	Compatible

Consideration should be given to the benefits and risks of harm of treatment in both the mother and child prior to initiating therapy, as well as the risks of harm of not initiating or continuing therapy. The breastfed infant should be monitored for potential adverse reactions, most commonly sedation, gastrointestinal effects (eg, diarrhoea) and irritability⁵.

In addition to possible effects in the breastfed infant, some medicines may affect milk production, often through hormonal regulation of lactation. For example, oestrogen-containing contraception is not recommended if the mother is breastfeeding as it reduces milk production. Domperidone and metoclopramide increase prolactin, which promotes lactation².

Breastfeeding mothers should use the lowest effective dose of a medicine for the shortest possible duration. For medicines with a short half-life, feeding the infant immediately prior to mother taking the next dose reduces the drug exposure in the infant.

If possible, medicines with short half-lives, high maternal protein binding, low oral availability and high molecular weight should be used.

References

1. Jayawickrama HS, Amir LH, Pirotta MV. 2010. GPs’ decision-making when prescribing medicines for breastfeeding women: Content analysis of a survey. BMC Research Notes doi: 10.1186/1756-0500-3-82.
2. Amir LH, Pirotta MV, Raval M. 2011. Breastfeeding: Evidence based guidelines for the use of medicines. Australian Family Physician 40(9): 684-690.
3. Nice FJ, Luo AC. 2012. Medications and Breastfeeding. Journal of the American Pharmacists Association 52(1): 86-94.
4. Ilett KF, Kristensen JH. 1997. Drug distribution in human milk. Australian Prescriber 20(2): 35-40.
5. Berlin CM, Briggs GG. 2005. Drugs and chemicals in human milk. Seminars in Fetal & Neonatal Medicine 10: 149-159.
6. Medsafe. 2014. Drug Metabolism — The Importance of Cytochrome P450 3A4. Prescriber Update 35(1): 4–6. URL: www.medsafe.govt.nz/profs/PUArticles/March2014DrugMetabolismCytochromeP4503A4.htm (accessed 20 May 2015).
7. World Health Organization. 2002. Breastfeeding and maternal medication: Recommendation for drugs in the eleventh WHO model list of essential drugs www.who.int/maternal_child_adolescent/documents/55732/en/ (accessed 09/04/2015).
8. American Academy of Pediatrics. 2001. The Transfer of Drugs and Other Chemicals Into Human Milk http://pediatrics.aappublications.org/content/108/3/776.full.pdf+html (accessed 10/04/2015).