Download medication use in breastfeeding women

National Medicines
Information Centre
VOLUME 20
NUMBER 2
2014
ST. JAMES’S HOSPITAL • DUBLIN 8
TEL 01-4730589 or 1850-727-727 • FAX 01-4730596 • www.nmic.ie
MEDICATION USE IN BREASTFEEDING WOMEN
Many medicines are safe for use by breastfeeding women
The risks and benefits of each medicine should be evaluated for the individual mother
and the infant
Caution is required when prescribing to mothers with premature or low birth weight
infants, particularly when multiple medicines are required
Safety information in standard sources may be limited and is often conflicting; the
NMIC has access to specialist lactation sources and is well placed to answer any
enquiries
INTRODUCTION
The importance of breastfeeding for both infants and mothers is well known.1-4 Exclusive breastfeeding for the
first 6 months of life, followed by continued breastfeeding while complementary foods are introduced until the
child is 2 years of age and beyond, is recommended by many national and international agencies, including
the Department of Health and Children.3,5 Breastfeeding is particularly beneficial for pre-term infants.3 The
incidence of breastfeeding in Ireland has increased in recent years, even though Ireland has one of the lowest
breastfeeding rates in Europe.6-8 Figures from 2010 found that 46% of infants in Ireland were exclusively
breastfed in the first 48 hours, compared to 81% in the United Kingdom and 87% in Poland.7
During the post-partum period, women frequently need medical care and may require medications for conditions
such as infection, depression and pain.9-11 In addition, women with chronic medical conditions may require
medication during this period. Evidence suggests that >50% of all breastfeeding women use some medicines.4,10
It is generally agreed that all medications transfer into human milk to some extent, however it is usually quite
low (<10% of the maternal dose) and is seldom clinically relevant for the infant.9,12-14 Often however, many
women are advised or decide themselves to discontinue breastfeeding in order to take a medication even though
it may be possible for breastfeeding to continue;2,9,11,12,14-16 others may not receive or take a medication they
require due to the potential risk to the infant. 11
The decision to use pharmacological therapy in breastfeeding women must balance the benefits of
therapy for the mother and continuing breastfeeding for the mother and infant against the potential risk
of drug exposure to the infant.2,3,16,17 There is a limited number of agents that are absolutely contraindicated
in breastfeeding women including anti-neoplastic agents and radioactive pharmaceuticals.18 However, it can
be challenging to determine which medications are suitable for breastfeeding women as different information
sources can give conflicting recommendations.9,11,13 Usually there are more data on older medicines, which are
generally preferred. This bulletin outlines the points to consider when prescribing for a breastfeeding woman,
and addresses some of the frequently asked questions (FAQs) received by the National Medicines Information
Centre (NMIC) on this topic.
GENERAL CONSIDERATIONS
Drug, infant and maternal factors are considered when assessing the risks and benefits of prescribing to
breastfeeding women.17
Drug Factors: The maternal plasma concentration of a drug is one of the most important factors in the exposure
of a breastfed infant to the drug; most medicines enter human milk by passive diffusion.12,15,19 As the maternal
plasma level of a drug increases, the breast milk level increases, and subsequently falls as the plasma level
falls.9,12 Drugs with long half-lives are more likely to accumulate in human milk.17 Exposure of the infant to a
drug can be reduced by avoiding breastfeeding at the time the drug reaches its maximum concentration in the
plasma and by using drugs with shorter half-lives.15 Drugs with high molecular weights (e.g. heparins, interferons
and insulin) are less likely to pass into breast milk.15 Highly lipid soluble drugs penetrate into breast milk in
higher concentrations than those that are not.12 Drugs which are highly protein bound (e.g. warfarin) have low
levels in breast milk.12 Breast milk is more acidic than plasma, therefore drugs with a high pH (e.g. barbiturates)
may concentrate more in breast milk.12,15 Drugs with a low oral bioavailability (e.g. omeprazole) do not enter
the infant’s bloodstream via breast milk,12 however they may affect the gastrointestinal tract causing diarrhoea,
constipation and occasionally pseudomembranous colitis.12,19 It is important to consider that medications which
are lipid soluble and centrally active that produce sedation or other neuroleptic effects in the mother, may
produce similar effects in the infant.12
One of the more popular methods for assessing infant risk is to estimate the Relative Infant Dose (RID),
which is available for many drugs. It provides a standardised method of relating the infant’s dose via breast
milk to the maternal dose.12,13,15 Many sources now suggest that medications with an RID of <10% are generally
considered safe for breastfeeding full term infants.12,20 It is important however that each situation is evaluated
individually according to the overall toxicity of the medication and to consider other factors, particularly
infant factors,13 as discussed below.
Infant factors: The most important infant factors to consider are the age and maturity of the infant.2
Adverse events associated with drug exposure via lactation occur most often in infants < 2 months and rarely
in infants > 6 months.17 Newborns and especially premature infants are more at risk due to immaturity of
the liver and kidneys and subsequent clearance of some medications; the competency of barriers such as the
blood-brain barrier is another factor.2 In addition, drug metabolites may also have pharmacological effects and
medications with long half-lives may accumulate, particularly in younger or premature newborns. Infants
can be categorised as low (age 6-18 months), moderate (full-term infants age 2 weeks – 6 months) or high
risk (premature, newborn or infants with medical conditions such as renal impairment) of adverse effects from
exposure to medications from breast milk.13 Older infants typically breastfeed less often; this makes it easier
to time the administration of the mother’s dose where appropriate. Also, medications that are considered safe
for infants (i.e. those that are used therapeutically in the infant), are generally considered to be low risk when
given to the breastfeeding woman.2
Maternal factors to consider include the severity of the condition being treated and the risk to the mother
of not receiving medication.17 It is also important to consider whether the medication is required for short-term
or long-term use. Medicines penetrate into milk more during the colostrum period (days 0-3 after parturition)
than in mature milk, however the absolute dose transmitted is low due to the low volumes of milk produced
during this period (30-100 mL/day).12,13,15 Mature milk volume is usually highest in the early morning while the
fat content of milk is usually highest in the late morning.15 For some medicines e.g. once-daily short acting
medicines, mothers are advised to breastfeed first, and then take their medicine, thereby decreasing the
likelihood of overexposing the infant to the medicine.15
In summary, many medicines are safe to use while breastfeeding; table 1 summarises the key points about
medicine use in breastfeeding.
Table 1: Key points about Breastfeeding and Medicines9,12
• Many medicines are safe in breastfeeding, however non-essential medicines should be avoided
• Where possible drugs with short half-lives, high protein binding, low oral bioavailability and high molecular
weight are preferred
• The age and weight of the infant needs to be considered; caution is required for premature infants and neonates
• Medicines that are safe to use in infants are generally safe to use in breastfeeding women
• Medicines for which there is long-term experience of use in clinical practice rather than newer medicines are
generally preferred
• Medicines used in the first 3-4 days post-partum generally produce subclinical levels in the neonate due to the
limited volume of milk produced during this period
• Discontinuing breastfeeding for some hours/days may be required for a small number of medicines
FREQUENTLY ASKED QUESTIONS ON THE SAFETY OF
MEDICINES IN BREASTFEEDING WOMEN
Many medicines are not authorised for use in breastfeeding, however safety information for most medicines
is available. The NMIC frequently receives enquiries on the use of medicines in breastfeeding women from
healthcare professionals. The resources that the NMIC use include the Summary of Product Characteristics,
standard medicines information sources, specialist lactation sources and the recent literature. The remainder of
this bulletin will discuss some FAQs on the use of medicines in breastfeeding women. For additional information
on these FAQs or other therapeutic areas, please contact the NMIC.
Use of antibiotics in breastfeeding women
Post-partum women may require treatment with antibiotics for conditions such as mastitis, endometritis and
urinary tract infection.
Penicillins and cephalosporins: Penicillins (RID 1%) and cephalosporins (RID 4%) have been well studied
in breastfeeding and are considered safe in breastfeeding women.1,2,12,13,21,22,23 They are frequently used for the
treatment of mastitis.22 There is less information available with third generation cephalosporins.24 Adverse events
reported in exposed infants include diarrhoea and oral candida infection.1,12,24
Macrolides: Low levels of the macrolides erythromycin (RID 2%), clarithromycin (RID 2%) and azithromycin
(RID 6%) are found in breast milk and are considered by many sources as compatible with breastfeeding
women.12,21-24 There are some epidemiological data to suggest an association between infants exposed to
macrolides (particularly erythromycin) and pyloric stenosis.12,21,24,25
Metronidazole (RID 13%) is used to treat specific infections in premature neonates, infants and children.12
Topical and vaginal formulations of metronidazole are suitable to use in breastfeeding women as maternal
systemic absorption is limited.1,12,13,21 Breastfed infants receive metronidazole in doses less than those used
to treat infections in infants when metronidazole is given orally or intravenously to breastfeeding women.13,21
Historically, there has been a concern regarding infant exposure to metronidazole via breast milk, due to the
findings of genotoxicity and carcinogenicity in animals,13,21,23 however the relevance of this is unknown in
humans.22 In addition, the routine clinical use of metronidazole suggests that the previous concerns were largely
overstated and that short-course maternal metronidazole use in breastfeeding should be well tolerated without
the need to discontinue breastfeeding.22,24,25 Some sources do recommend discontinuing breastfeeding for 12-24
hours after oral single-dose (2g) maternal metronidazole treatment.13,21 Case reports of candida infections and
diarrhoea have been reported in infants exposed to metronidazole.21,26
Tetracyclines: Some sources state that tetracyclines are contraindicated in breastfeeding women due to concerns
regarding teeth discolouration or tetracycline bone deposition in the infant.23,27-29 However other sources advise that
if other antibiotics are not appropriate, short term use (<3 weeks) may be acceptable, as the transfer into breast milk
is low and absorption is inhibited by the calcium in the breast milk (especially for the older tetracyclines).1,2,12,21-24
Quinolones: Many sources do not recommend quinolones for breastfeeding women; their use in animal studies
has been associated with arthropathy.2,13,23 Short-term use of quinolones may be acceptable (calcium in the
milk may interfere with absorption),1,12,21,22 however it is preferable to use an alternative antibiotic if possible.21
Quinolones should be avoided in breastfeeding mothers of infants with G6PD deficiency and used with caution
where the infant has epilepsy.24
Practice point: Breastfed infants exposed to antibiotics via breast milk should be monitored for changes
to gastrointestinal flora (e.g. diarrhoea, vomiting, oral candidiasis) and allergic reaction.9,23
Use of antifungals in breastfeeding women
Women frequently require antifungal therapy in the post-partum period. The use of topical antifungal therapy such
as clotrimazole and miconazole is considered acceptable in breastfeeding women, as there is minimal maternal
absorption.2,12,21 Topical use of ketoconazole and terbinafine if required is considered low risk but should be
avoided on the nipples and breast.12,21 If local treatment is ineffective; oral fluconazole is the preferred systemic
antifungal which is considered acceptable for short-term use.2,12,21,23,24 Even though the RID of fluconazole has
been estimated to be up to 22%,12 the amounts excreted in breast milk are less than the neonatal fluconazole
dose.21 One source advises that it should be taken at night after the last breastfeed.2 The exposed infant should
be monitored for gastrointestinal disturbances.24
Use of antidepressants in breastfeeding women
Post-partum depression affects up to 20% of mothers and can have devastating effects on the mother-infant
relationship if left untreated.4,13,30,31 Not all women with depression require pharmacotherapy; for those who do
antidepressants are an effective option.32,-34 Most antidepressants are excreted in low concentrations in breast
milk.17,30 Currently there is little evidence to suggest that exposure to antidepressants through breastfeeding has
any serious effects in infants even though long-term neuro-developmental effects have not been adequately
studied.4,17,30,31 Advice from secondary psychiatric care should be considered before starting antidepressants
in breastfeeding women.32 The choice of the antidepressant should be based on clinical factors, including
previous effective treatments.31 The antidepressant should be started at the lowest effective dose and increased
slowly. The clinical condition of the mother and infant should be monitored, particularly for low birth weight
and premature infants.31,32
Selective serotonin reuptake inhibitors: (SSRIs) are the most frequently prescribed antidepressants and are the
class for which the most evidence exists.12,13,34 SSRIs have relatively long half-lives and drug accumulation can
occur in neonates and young infants.32 Many sources recommend sertraline (RID 2%) and paroxetine (3%)
as the preferred first choice SSRIs to use during breastfeeding;4,21,24,30-36 compared to other SSRIs they have
shorter half-lives and lower passage into breastmilk.24 Adverse events associated with infant exposure to SSRIs
via breast milk include irritability, decreased feeding and sleep problems.37 These are more often reported after
exposure to fluoxetine (RID 2-15%) (which has a half-life of up to 6 days)12,35 and citalopram (RID 4%),30 both
of which are best avoided.21,24
Tricyclic antidepressants (TCAs) are prescribed less often than SSRIs due to concerns about maternal toxicity.13,24
TCAs except doxepin can be used to treat depression in breastfeeding women, however the non-sedating TCAs
such as nortriptyline or imipramine (not licensed in Ireland) are the preferred TCAs.21,31,32
Other antidepressants: There are less data available on other antidepressants such as venlafaxine (RID 8%), duloxetine
(1%) and mirtazapine (RID 6%), which are generally not recommended as first choice antidepressants.21,24,32,35,37
Practice points: If a woman is already on an effective antidepressant, prescribers should continue with
that antidepressant rather than switching to an alternative.21,30,32 All infants exposed to antidepressants
in breast milk should be monitored for drowsiness, poor feeding, irritability, or behavioural effects.4,24
Use of analgesics in breastfeeding women
Analgesics are one of the most commonly used medications while breastfeeding.
Paracetamol is regarded as an acceptable analgesic to use in breastfeeding women.2,9,12,17,23 The amount of
oral paracetamol in breast milk (RID 9%) is much less than doses given to infants.12,13,21 Some reports suggest
that exposure to paracetamol in the first year of life is a risk factor for asthma, but a causal link has not been
established.12,21
Non-steroidal anti-inflammatory drugs (NSAIDs) pass into breastmilk in small amounts and are generally
considered compatible with breastfeeding.2,13 Ibuprofen which is frequently prescribed for infants and has a
short half-life (RID 1%), is preferred to other NSAIDs, such as naproxen (RID 3%), which has a long half-life
(there has been a reported case of bleeding and anaemia in an infant exposed to naproxen).1,2,12,13,17,21,23
Aspirin (RID 10.5%) is best avoided as an analgesic in breastfeeding women; aspirin use in children has been
associated with Reye’s syndrome.13,21 Some experts recommend that low-dose aspirin (75-162mg per day) may
be used as antiplatelet therapy in breastfeeding women where indicated; breastfeeding should be avoided for
up to 2 hours after administration to reduce the antiplatelet effect in the infant.12,21
Opioids: Maternal use of opioid analgesics during breastfeeding can cause infant drowsiness and central
nervous system depression; non-opioids should be used when possible.21 Newborn infants in particular are
sensitive to the effects of opioids, as they have reduced clearance of opioids up to the age of 6 months.21 If
required, opioids should be used with caution in breastfeeding women and at the lowest dose for the shortest
duration possible.17 The infant should be closely monitored for sedation and other adverse effects (e.g. feeding
difficulties).13,23 Codeine (RID 8%), a mild opioid, is contraindicated in breastfeeding women.38,39 There have
been adverse events (including apnoea and death) reported in codeine-exposed breastfed infants, particularly in
breastfeeding women who are ultra-rapid metabolisers of codeine.1,12,16,17,39 Tramadol (RID 3%) is considered
by some experts as acceptable to use short-term in breastfeeding women;12,21,18,40 exposed infants should be
monitored for sedation and feeding difficulties.1,2,12,21
Use of antihistamines in breastfeeding women
Antihistamines may be required by breastfeeding women for symptoms including pruritus and allergic rhinitis.
First generation antihistamines (chlorphenamine and diphenhydramine) should be used with caution as
they easily cross the blood-brain barrier and are known for their sedating effects.12,14,21 Second generation nonsedating antihistamines such as cetirizine and loratadine do not cross the blood-brain barrier as readily, and are
preferred.12,14 Infants should be monitored for signs of excessive irritability, jitteriness and drowsiness.12,14,21
Use of antihypertensives in breastfeeding women
In the postnatal period some breastfeeding women may require antihypertensive medication. Many of these
medications are suitable to use in breastfeeding, however there are some medications which are preferred.13
Beta (β) blockers: Various sources recommend that propranolol (RID 0.3%), labetolol (RID 0.6%) and metoprolol
(RID 1%) are the preferred β blockers for breastfeeding women.1,2,12,13,21,41 Other β blockers such as atenolol
which has low protein binding and is primarily renally excreted, have been associated with adverse effects in
infants and should be avoided.1,13,16,23 Monitoring of the infant for hypotension, bradycardia and lethargy
is recommended when using β blockers during breastfeeding.1,12,13
Methyldopa is one of the preferred antihypertensives in breastfeeding women;1,2,12 low levels of methyldopa
(RID 0.1-0.4%) are found in breastfed infants and are not expected to cause adverse effects.12,21,23
Calcium antagonists: Many sources include nifedipine (RID 2.3%), verapamil (RID 0.15%) and diltiazem (RID
0.9%) as the preferred calcium antagonists to use in mothers of breastfed infants.1,2,12,13,21,41 Exposed breastfed
infants to calcium antagonists should be observed for bradycardia and hypotension.12
Angiotensin converting enzyme inhibitors (ACEIs): The ACEIs with the most amount of data available
on breastfeeding are captopril (RID 0.0002%) and enalapril (RID 0.175%), which are amongst the preferred
ACEIs in breastfeeding women.2,12,13,21,40 They are not recommended however, in the first weeks after delivery
due to concerns of profound hypotension, particularly in preterm infants.42 Infants exposed to ACEIs, should
be observed for hypotension.12
There is insufficient evidence on the safety of angiotensin receptor blockers (ARBs) in breastfeeding women
to recommend their use.2,13,41
SUMMARY
• The benefits of breastfeeding for mothers and infants are well known and should
•
•
•
•
be promoted
Many medicines can be used safely in breastfeeding women
The age and maturity of the infant should be considered when a breastfeeding
woman requires pharmacotherapy
The clinical condition of the mother and infant should be monitored, particularly
for low birth weight and premature infants
There are many sources of information available on the use of medicines in
breastfeeding women; the NMIC has access to specialist sources and is happy to
answer enquiries on this topic
FOR PERSONAL USE ONLY. NOT TO BE REPRODUCED WITHOUT PERMISSION OF THE EDITOR
List of references available on request. Date of preparation: May 2014
Every effort has been made to ensure that this information is correct and is prepared from the best available resources at our disposal at the time of issue.
Prescribers are recommended to refer to the individual Summary of Product Characteristics (SmPC) for specific information on a drug.
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