Eur J Clin Pharmacol (2014) 70:1361–1366
DOI 10.1007/s00228-014-1738-2
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Drug-induced adverse reactions via breastfeeding: a descriptive
study in the French Pharmacovigilance Database
Caroline Soussan & Aurore Gouraud & Ghyslaine Portolan & Marie-Joseph Jean-Pastor &
Caroline Pecriaux & Jean-Louis Montastruc & Christine Damase-Michel &
Isabelle Lacroix
Received: 10 April 2014 / Accepted: 18 August 2014 / Published online: 4 September 2014
# Springer-Verlag Berlin Heidelberg 2014
Abstract
Purpose Most drugs are excreted in maternal milk and may
therefore be ingested by children during breastfeeding. Data
concerning the safety of the use of drugs by breastfeeding
women are patchy, and almost nothing is known about this
issue for many drugs.
Methods The aim of this study was to describe the adverse
drug reactions of drugs transmitted in breast milk on the basis
of the data collected in the French Pharmacovigilance
Database. All spontaneous reports of adverse drug reactions
(ADRs) in breastfed infants recorded in the National
Pharmacovigilance Database by the 31 French regional
pharmacovigilance centres between 1984 and June 2011 were
investigated.
Results Between January 1985 and June 2011, 276 adverse
drug reactions in 174 breastfed children were notified to the
French Pharmacovigilance Network. The most frequently re-
ported adverse drug reactions were neurological (28.6 %) and
gastrointestinal (20.3 %). Sixty-five of the adverse drug reac-
tions recorded were considered to be serious (37.4 %). The
results of our study confirm that certain drugs were frequently
implicated in serious adverse drug reactions. Two cases of
ADRs (1.1 %) had a ‘certain’ causality score (I4) and 13
(7.5 %) a ‘likely’ score (I3). The suspected drugs include
antiepileptic drugs, opiate analgesics and benzodiazepines.
These results also demonstrate that some drugs that were
thought to be anodyne or for which no data were available,
Electronic supplementary material The online version of this article
(doi:10.1007/s00228-014-1738-2) contains supplementary material,
which is available to authorized users.
C. Soussan : A. Gouraud : G. Portolan : M.<J. Jean-Pastor :
C. Pecriaux : J.<L. Montastruc : C. Damase-Michel : I. Lacroix (*)
CHU de Toulouse, Université de Toulouse, Inserm 1027, Toulouse,
France
e-mail: isabelle.lacroix@univ-tlse3.fr
such as ketoprofen and hydroxyzine, may be implicated in
adverse effects. Finally, these data show that certain drugs,
like pseudoephedrine, which should not be used during
breastfeeding, were nevertheless implicated in several of the
adverse drug reactions recorded.
Conclusion This study shows that ADR via breastfeeding are
rarely reported due to low awareness or low occurrence of
ADR via breast milk. These results highlight the need for
additional pharmacokinetic, clinical and epidemiological
studies, given the paucity of published data. They also dem-
onstrate the need to improve information for the general
public about drugs and self-medication during breastfeeding.
Keywords Drugs . Breastfeeding . Adverse drug reactions
Introduction
The frequency and duration of breastfeeding are lower in
France than in other European countries, with almost 60 %
of mother’s breastfeeding [1]. These women may be exposed
to various drugs, particularly during the postdelivery period.
A few kinetic data are available, but little is known about
passage into breast milk for almost half the drugs currently on
the market. Kinetic data and follow-up for breastfed children
are even rarer [2]. There are few data about drugs during
lactation, and the current available advice on the use of drugs
during breastfeeding, given by different accredited sources,
presents some contradictions [3, 4]. Nevertheless, many situ-
ations may lead to the ingestion of drugs by the mother during
the breastfeeding period. A study in the Toulouse area has
shown that breastfeeding mothers do not seem to take any
fewer drugs than the general population during the 2 months
after delivery (2.4±1.3 versus 2.8±1.4; p>0.05) [5]. Few data
have been published on adverse drug reactions on breastfed
infants. Only one prospective study on adverse reactions in
1362
breastfed infants exposed to maternal medication was pub-
lished in 1993 [6]. Authors reported no major adverse reac-
tions in a cohort of 838 infants but 11.2 % of minor drug
adverse effects. A review [7] analysed the 100 adverse events
in infants caused by medications in breast milk identified in
the literature (studies and cases reports). Authors underlined
that CNS drugs accounted for half of the ADRs via
breastfeeding and 78 % of cases were in infants 2 months or
younger.
The objective of this study was to describe the notifications
of adverse drug reactions for breastfed children reported to the
French Pharmacovigilance Database.
Materials and methods
We performed a descriptive study on data from the French
Pharmacovigilance Database (FPVD). This database includes
all spontaneous adverse drug reaction (ADR) reports regis-
tered since 1984 in France. According to French law, every
health practitioner must report ‘serious’ or ‘unexpected’ ad-
verse drug reactions to their Regional Pharmacovigilance
Centre (31 centres in France). ‘Serious’ adverse drug reactions
are defined as any untoward medical occurrence that, at any
dose, results in death, requires hospital admission or the
prolongation of hospitalisation for patients already in hospital,
results in persistent or significant disability/incapacity, is life
threatening, results in cancer, congenital abnormalities or birth
defects or any medical event that would be regarded as serious
if it had not responded to acute treatment.
For each ADR report, information about the patient (age,
sex, medical history), drug exposure (to the suspected drug
and other associated non-suspected drugs) and ADR charac-
teristics (‘serious’ or ‘non-serious’, ‘expected’ or ‘unexpect-
ed’, causality score, outcome) are recorded in the FPVD. A
detailed summary of the clinical description of the patient is
added to the end of each pharmacovigilance case report. The
route of administration, including breastfeeding, is specified.
In the FPVD, ADRs are encoded according to the Medical
Dictionary for Regulatory Activities (MedDRA) classifica-
tion. We categorised the medicines consumed by the women
in accordance with the WHO’s Anatomical Therapeutic
Chemical (ATC) classification. The French imputability
method, which takes into account chronological (graded
from C0 to C3) and semiological (graded from S1 to S3)
data, was used to assess the intrinsic or case-related imput-
ability [8].
All spontaneous reports of ADRs in breastfed infants
recorded in the National Pharmacovigilance Database by
the 31 French regional pharmacovigilance centres between
1984 and June 2011 were investigated. The variables men-
tioned above were analysed. Analyses were performed using
Epi Info version 6.
Eur J Clin Pharmacol (2014) 70:1361–1366
Results
The FPVD contained a total of 276 adverse drug reactions
occurring in 174 breastfed children. ADRs were reported by
healthcare professionals in 88.7 % of cases and by patients in
11.3 %.
Study population
The sample of children studied consisted of 53.3 % girls and
46.7 % boys. The mean age of the children was 7.0±9.5 weeks
[1 day–2 years]; 63 % had less than 1 month, 37 % from
1 month to 2 years. Their mean weight was 3,864±1,327 g
(range 2,200 to 8,000 g), and their mean height was 49.4±
3.0 cm (range 43 to 55 cm).
Types of adverse drug reaction
The most frequently reported adverse drug reactions (Fig. 1)
were those concerning the central nervous system (behaviour-
al problems, sedation and insomnia), followed by digestive
problems (diarrhoea, vomiting). Sixty-five (37.4 %) cases of
adverse drug reactions were considered to be serious. Adverse
drug reactions on the central nervous system also predominat-
ed among serious adverse effects, themselves accounting for
more than a third of all serious adverse reactions (sedation,
loss of consciousness). ADRs resolved in 79.3 % of cases, and
outcome was unknown in 20.7 %.
Drugs involved
‘Central nervous system’ drugs were implicated in more than
a third of all cases of adverse effects in breastfed children
(Fig. 2). The drugs involved were mostly antiepileptic drugs,
anxiolytics and opiate analgesics. ‘Alimentary tract and me-
tabolism’ drug class was the second most frequent class of
drugs implicated, followed by anti-infective drugs, such as
beta-lactams and macrolides in particular, in third place.
‘Respiratory system’ drugs were in fourth place (mostly
atropinic antihistamines and pseudoephedrine).
‘Cardiovascular system’ drugs were in fifth place (with beta-
blockers at the top of the list). Table 1 provides a list of the
drugs most frequently implicated in adverse drug reactions in
breastfed children.
At the top of the list, with 15 notifications of adverse
reactions, is paracetamol, which was often associated, in spe-
cialist formulations, with a more suspect active ingredient,
such as dextropropoxyphene. The second most frequently
implicated drug was dextropropoxyphene itself, an opiate
analgesic responsible for cases of hypotonia, apnoea, respira-
tory distress, bradycardia and constipation. Of the 11 notifi-
cations of adverse reactions, nine were considered serious. It
was followed by hydroxyzine, an antihistamine implicated in
 A % of drugs N
lim N er
en er vo
ta vo us % of ADRs
r s

0
5
10
15
20
25
30
35
40
y us ys
te
tr Sy
ac m

0
5
10
15
20
25
30
35
40

st G
ta em as di
nd Sk tr so
m in oi rd
an nt er
et
ab d e st s
in
34.8

ol su
is m b cu al
A an t di
so
nt
i-i eo rd
nf us er
R ec tis s
tiv
20.3

es es su

Fig. 2 Most ADR-induced ATC classes

pi ed
G ra C
en to ar iso
C ry
Eur J Clin Pharmacol (2014) 70:1361–1366

ito di rd
-u ar sy ov er
ri di st as s
ov em cu
6.5

Fig. 1 ADRs classified by System Organ Class

na
ry as la
sy c ul rd
st a H iso
em rS ep rd
ys at er
an te ob s
d m ili
5.8

se ar
x y
M h or di
us m R so
A Bl cu on es rd
lo pi er
nt
in
oo
d s ke
es ra s
5.8

eo an le to
pl
as d ta
ls
ry
bl di
tic oo ys so
an d te
m
rd
d fo G er
im rm en s
m
4.7

in
g R e ra
un or en ld
Sy om ga al is o
st od ns an rd

ADRs
em ul d

ATC classes
a er
ic tin ur
in s
g
4.7

ho ar
rm ag y
on en di
al ts so
pr al rd
ep im er
en s
4

an ar ta
tip at ry
ar io
as ns di
iti so
cp rd
er
ro s
4

du
ct
Se s D
ns
or ec O
y re th
as er
or
ga e d s
m
3.6

D ns ilk
er
m se
at cr
ol et
og io
ic
al Bl n
s
3.3

o od
di
O so
th rd
er er
s s
2.5
1363
1364 Eur J Clin Pharmacol (2014) 70:1361–1366

Table 1 Most often prescribed drugs factor is not limiting in the framework of this study, which was
Drugs Number of cases Percent descriptive in nature. The exhaustiveness of notifications is
not an essential prerequisite for obtaining a general view of the
Paracetamol 15 11.3 involvement of drugs in the occurrence of adverse drug reac-
Dextropropoxyphene 11 8.3 tions in breastfed children. The quality of Pharmacovigilance
Hydroxyzine 8 6.1 notifications is variable and some data (e.g. antecedents, con-
Ketoprofen 8 6.1 sumption of other products) may differ in their degree of
Amoxicillin + clavulanic acid 6 4.5 completeness between observations. For example, it is not
Ascorbic acid 6 4.5 specified, in the National Pharmacovigilance Database, if
Lamotrigine 6 4.5 breastfeeding was exclusive or complementary. However, this
Valproic acid 5 3.7 can affect the amount of drugs into the milk and the occur-
Levonorgestrel 5 3.7 rence of adverse drug reaction.
Ibuprofen 5 3.7 Despite the long study period, the total number of adverse
Flavonoid 5 3.7 drug reactions in breastfed children recorded was small (174
Iron 5 3.7 notifications over 26 years). There are several possible reasons
Clonazepam 5 3.7 for this. Firstly, for most drugs, the amount of the drug
Amoxicillin 5 3.7 received via breast milk would probably be too small to
Pseudoephedrine 4 3.0 produce an adverse reaction [4–10]. Secondly, mothers and
Carbamazepine 4 3.0 healthcare professionals might not necessarily make the con-
Vitamin A 3 2.2 nection between maternal drug intake and the occurrence of an
Topiramate 3 2.2 adverse drug reaction in the child, particularly if it is not
Clorazepate 3 2.2 severe. The considerable underreporting of adverse drug re-
actions, as described above, is also relevant. Otherwise, the
score of causality is rarely high: only 8.6 % of cases had a
‘likely’ or ‘certain’ causality score. This may be due to the
cases of sedation in particular. This list also includes non- difficulty in assessing ADR in breastfed infants.
steroidal anti-inflammatory drugs, including ketoprofen (in Two-thirds of the cases of reported adverse drug reactions
fourth place), which was implicated in eight cases of adverse involved neonates (less than 1 month old). Same, Anderson
reactions, including several serious cases: one oesophageal et al. [7], who analysed all published studies and case reports
ulcer, one erosive gastritis, one meningeal haemorrhage and on adverse events in infants caused by medications in breast
one renal insufficiency. The list also includes several antiep- milk, showed that 63 % of reported cases were in neonates.
ileptic drugs: lamotrigine, which was associated with sedation, The metabolic system is immature during the neonatal period
hypotonia and weight loss; valproic acid, clonazepam; carba- resulting in a longer half-life of drugs in neonates than in older
mazepine and topiramate. Vitamins and mineral (ascorbic children. This may account for the higher frequency of noti-
acid, iron, vitamin D and vitamin A) were always associated fication of adverse drug reactions in neonates. The mean
with other more suspected drugs. Two cases of ADRs (1.1 %) weights and heights of the affected children were lower than
had a ‘certain’ causality score (I4) and 13 (7.5 %) a ‘likely’ would be expected given the mean age of the children. Indeed,
score (I3). Cases of serious ADRs with the higher causality based on body mass index curves, children of this age should
scores (I3 ‘likely’ and I4 ‘certain’) were presented in Table 2. weigh almost a kilo more than the actual weight of these
children [11]. This may reflect a higher rate of prematurity
among these children than in the general population [1], and
Discussion prematurity has indeed been identified as a factor of suscep-
tibility to drugs in children.
This study shows that ADRs via breastfeeding are rarely Despite the position of paracetamol at the top of the table of
reported. At least, two-thirds of reported cases were in neo- drugs most frequently identified in adverse drug reactions, this
nates. ‘Central nervous system’ drugs accounted for more than drug was almost invariably not itself directly implicated in the
a third of all ADRs. effect, but rather was a component of a formulation also
Our study is subject to several limitations relating to the use contained a more suspect active ingredient (such as
of the National Pharmacovigilance Database. There is known dextropropoxyphene in particular). The list of drugs respon-
to be considerable underreporting of adverse drug reactions, sible for adverse effects in breastfed children includes ‘expect-
and the adverse reactions listed in the FPVD are thought to ed drugs’, for which data consistent with our observations in
account for only about 6 to 10 % of the total number of this study have already been published; ‘unexpected drugs’,
adverse drug reactions occurring in reality [9]. However, this for which published data are currently reassuring or for which
Eur J Clin Pharmacol (2014) 70:1361–1366 1365

Table 2 Serious ADRs with the higher causality scores I3 (‘likely’) and I4 (‘certain’)

Causality score Suspected drugs Associated drugs ADRs Sex Age Outcome

I4 (certain) Diazepam – Hypotonia apnoea F 2 years Recovered fully

Clonazepam – Hypotonia somnolence apnoea F 2 months recovered fully
I3 (likely) Interferon-α2b Aspirin desogestrel Vomiting M 1 month Recovered fully
Propranolol – Bradycardia F 2 days Still recovering at the time of ADR
reporting
Framycetin – Bradycardia respiratory distress M 3 days Recovered fully
Bromazepam – Constipation apathy hypotonia M 2 months Recovered fully
Carbimazole Levothyroxine Neutropenia F 15 days Still recovering at the time of ADR
reporting
Dextropropoxyphene Paracetamol Hypotonia weight loss F 13 days Recovered fully

little or no published information is currently available and
‘drugs to avoid’, for which the risk was always higher than the
benefit.
Some drugs are known to have unfavourable pharmacoki-
netic and pharmacological profiles during breastfeeding. In
our study, as in the Ito et al study [6], expected and serious
adverse drug reactions for a certain number of these drugs
were observed. This was the case for antiepileptic drugs,
which constituted the drug class most frequently implicated
in the occurrence of adverse reactions. Antiepileptics are
among the drugs for which use during breastfeeding can be
most strongly questioned, due to their pharmacokinetics and
their potentially serious adverse reactions. Lamotrigine was
the antiepileptic drug most frequently implicated in the occur-
rence of adverse reactions. It was implicated in several ‘ex-
pected’ serious adverse drug reactions, such as depression of
the central nervous system and liver damage. Apnoea, with-
drawal reactions and an increase in hepatic enzyme activity
have been reported in children breastfed by mothers receiving
lamotrigine treatment [12–14]. In terms of pharmacokinetics,
lamotrigine is found in the serum of children breastfed by
treated mothers, at concentrations of up to 74 % of the serum
concentration of the drug in the mother [15].
Dextropropoxyphene, an opiate analgesic withdrawn from
the French market in 2011, was also implicated in a large
number of adverse reactions in this study: all the adverse
reactions described were consistent with those well known
of opiates: apnoea, respiratory distress, sedation, bradycardia
and constipation. Cases of sedation, apnoea, bradycardia and
cyanosis after the use of dextropropoxyphene by the mother
have been also reported in the literature [4–16]. Codeine,
another weak opiate analgesic, has been implicated in the
death of one breastfed child [17]; the mother and child
belonged to a subpopulation of ultrarapid CYP2D6
metabolisers, and codeine is partly metabolised by the
CYP2D6 pathway, to yield morphine. In terms of pharmaco-
kinetics, despite the passage of only small quantities of
dextropropoxyphene into maternal milk [18], there remains a
risk of accumulation in the milk of the active metabolite of this
drug, norpropoxyphene, which has a long clearance half-life.
These examples highlight the problem of using opiate analge-
sics during breastfeeding, particularly for long-term treatment.
Benzodiazepines, which are known to pass into breast
milk, have been identified in cases of adverse reactions fol-
lowing exposure through breast milk [19]. Benzodiazepines
with a long half-life and active metabolites present the greatest
risk during the breastfeeding period. As in the Rubin et al.
study [19], we observed adverse reactions, mostly apnoea and
hypotonia, expected with this drug class.
Electronic supplementary material
Some of the other drugs identified were more ‘unexpected’.
This was the case, in particular, for ketoprofen, a non-steroidal
anti-inflammatory drug. In our study, it was the third in the list
of drugs most frequently implicated in adverse drug reactions.
Most of the adverse reactions it caused were serious and
typical of its pharmacological effects: oesophageal ulcer, ero-
sive gastritis, meningeal haemorrhage and acute renal insuffi-
ciency. No particular event has previously been reported in the
literature for children breastfed by mothers treated with
ketoprofen. A pharmacokinetic study has shown that only
0.3 % of ketoprofen passes into breast milk [20]; this study
was carried out in women just after delivery. It would be
interesting to obtain data about the passage of this drug into
breast milk in the longer term, given the disturbing nature of
the cases of adverse reaction we report.
Hydroxyzine was also characterised by the large number
and seriousness of the adverse reactions in which it was
implicated. Hydroxyzine is an antagonist of central and pe-
ripheral H1 receptors, with anticholinergic properties. In
France, it is indicated and often used as an anxiolytic. We
found no relevant published data for this drug, particularly as
concerns its passage into breast milk. Nevertheless, it was the
third most frequently implicated drug in adverse drug reac-
tions, with a frequency similar to that of ketoprofen. Half the
adverse reactions involving hydroxyzine was serious. The
adverse reactions recorded were consistent with the known
1366
mechanism of action of this drug: adverse central (sedation,
excitation), cardiovascular (malaise, with bradycardia and
cyanosis) and gastrointestinal (including constipation in par-
ticular) effects.
We also observed apparent adverse reactions of drugs for
which the benefit/risk ratio is not favourable in breastfeeding
women. These drugs were mostly available over the counter,
without a prescription. For example, pseudoephedrine,
pheniramine and oxomemazine are indicated for the treatment
of colds and coughs. As previously reported, we found that
pseudoephedrine was implicated in states of agitation in neo-
nates [6]. These drugs should be avoided during
breastfeeding, given the benign nature of their indications
and the potential adverse drug reactions they may cause.
Conclusion
This study describes, over a long period, the cases of adverse
drug reactions occurring in children breastfed by mothers
using drugs. Its results confirm that certain drugs should be
avoided during breastfeeding, or at least used with precaution
in certain circumstances. The drugs concerned include antiep-
ileptic drugs, opiate analgesics and benzodiazepines. The
results also show that other drugs that were thought to be
more anodyne, or for which no data are currently available,
may also be involved in adverse reactions and should there-
fore be avoided during breastfeeding, including ketoprofen
and hydroxyzine.
Finally, this study shows that certain drugs, such as pseu-
doephedrine, which should not be used by breastfeeding
women, were nevertheless involved in a number of the report-
ed adverse reactions. These findings highlight the need for
additional pharmacokinetic, clinical and epidemiological data,
given the scarcity of relevant published studies. They also
indicate that more and better information need to be provided
to the general public concerning drugs and self-medication
while breastfeeding.
References
1. Ministère de la Santé. Enquête nationale périnatale (2010) http://
www.sante.gouv.fr
Eur J Clin Pharmacol (2014) 70:1361–1366
2. Bavoux F, Elefant E (1989) Undesirable effects of drugs during
breast feeding. Rev Prat 39:881–882
3. Davanzo R, Dal Bo S, Bua J, Copertino M, Zanelli E, Matarazzo L
(2013) Antiepileptic drugs and breastfeeding. Ital J Pediatr 39:50
4. Sachs HC, Committee on drugs (2013) The transfer of drugs and
therapeutics into human breast milk: an update on selected topics.
Pediatrics 132:e796–e809
5. Lacroix I, Arrault-Olanora A, Berrebi A, Montastruc J-L, Damase-
Michel C (2005) Drug use during postpartum period: a comparative
study between lactating and non-lactating women. J Pediatr 18:379–
385
6. Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G
(1993) Prospective follow-up of adverse reactions in breast-fed
infants exposed to maternal medication. Am J Obstet Gynecol
168:1393–1399
7. Anderson PO, Pochop SL, Manoguerra AS (2003) Adverse drug
reactions in breastfed infants: less than imagined. Clin Pediatr
(Phila) 42:325–340
8. Begaud B, Evreux JC, Jouglard J, Lagier G (1985) Imputation of the
unexpected or toxic effects of drugs. Actualization of the method
used in France. Therapie 40:111–118
9. Begaud B, Martin K, Haramburu F, Moore N (2002) Rates of
spontaneous reporting of adverse drug reactions in France. JAMA
288:1588
10. Hale TW (2008) Medications and mothers ‘milk, tenth edition.
Pharmasoft publishing 1172p
11. Cole T, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a
standard definition for child overweight and obesity worldwide:
international survey. Br Med J 320:1240–1243
12. Newport DJ, Pennell PB, Calamaras MR, Ritchie JC, Newman M,
Knight B, Viguera AC, Liporace J, Stowe ZN (2008) Lamotrigine in
breast milk and nursing infants: determination of exposure. Pediatrics
122:223–231
13. Nordmo E, Aronsen L, Wasland K, Småbrekke L, Vorren S (2009)
Severe apnea in an infant exposed to lamotrigine in breast milk. Ann
Pharmacother 43:1893–1897
14. Precourt A, Morin C (2011) Use of lamotrigine during breastfeeding:
descriptive analysis of our population and report of five cases of
premature neonates. Breastfeed Med 6:S-18
15. Kacirova I, Grundmann M, Brozmanova H (2011) Serum levels of
lamotrigine in breastfeeding mothers, maternal milk and nursed
infants. Basic Clin Pharmacol Toxicol 109:135–136
16. Naumburg EG, Meny RG (1988) Breast milk opioids and neonatal
apnea. Am J Dis Child 142:11–12
17. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ (2006)
Pharmacogenetics of morphine poisoning in a breastfed neonate of
a codeine-prescribed mother. Lancet 368:704
18. Kunka RL, Yong CL, Ladik CF, Bates TR (1985) Liquid chromato-
graphic determination of propoxyphene and norpropoxyphene in
plasma and breast milk. J Pharm Sci 74:103–104
19. Rubin ET, Lee A, Ito S (2004) When breastfeeding mothers need
CNS-acting drugs. Can J Clin Pharmacol 11:257–266
20. Jacqz-Aigrain E, Serreau R, Boissinot C, Popon M, Sobel A, Michel
J, Sibony O (2007) Excretion of ketoprofen and nalbuphine in human
milk during treatment of maternal pain after delivery. Ther Drug
Monit 29:815–818