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LactMed |
UptoDate |
Briggs 10th Edi, 2015 |
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Pantoprazole |
Maternal pantoprazole doses of 40 mg daily produce low
levels in milk and would not be expected to cause any adverse effects in
breastfed infants. |
·
Pantoprazole is present in breast milk
(Plante 2004). ·
The relative infant dose (RID) of
pantoprazole was determined to be 0.14% when calculated using the highest
breast milk concentration located and compared to a weight-adjusted maternal
dose of 40 mg/day.* ·
The RID of pantoprazole was calculated
using a milk concentration of 0.036 mg/L, providing an estimated infant dose
via breast milk of 7.3 mcg; the authors calculated the estimated infant dose
by assuming 200 mL of breast milk would be ingested around the time of the
peak breast milk concentration. This milk concentration was obtained
following administration of a single maternal dose of oral pantoprazole 40
mg. Peak concentrations appeared in the breast milk 2 hours after the dose;
pantoprazole was undetectable in breast milk by 5 hours postadministration.
No adverse events were reported in the mother or infant for the 2 weeks
following administration (Plante 2004). ·
The acidic content of a breastfed
infant's stomach may potentially inactivate any pantoprazole ingested via
breast milk (Plante 2004). According to the manufacturer, the decision to
breastfeed during therapy should consider the risk of infant exposure, the
benefits of breastfeeding to the infant, and benefits of treatment to the
mother. |
Limited Human Data—Probably Compatible ·
Small amounts of pantoprazole are
excreted into breast milk. A 43-year-old mother, partially nursing a healthy
10-month-old, 8.2-kg, female infant was given a single 40-mg enteric-coated
pantoprazole tablet (16). Breastfeeding was held while nine samples of
maternal serum and six of breast milk were obtained over a 24-hour interval.
The milk samples, about 10 mL each, were obtained at 0, 2, 4, 6, 8, and 24
hours postdose. Pantoprazole was detected only in the 2-hour (0.036 mg/L) and
4-hour (0.024 mg/L) samples, resulting in an estimated AUC of 0.103 mg·hr/L.
The milk AUC was about 2.8% of the AUC for plasma. The peak maternal plasma
concentration, 1.65 mg/L, occurred at 2 hours, but the levels were <0.025
mg/L at 8 and 24 hours postdose. If the infant had been nursing, the authors
estimated that the infant dose would have been ≤0.14%
of the weight-adjusted maternal dose (16). ·
The results of the above case are
consistent with the relatively low molecular weight (about 432 for the
hydrated form) that suggests pantoprazole will be excreted into breast milk. ·
In addition, pantoprazole is unstable at
acidic pH so the amount actually absorbed by the infant may have been less
than estimated. |
|
Omeprazole |
Limited information indicates that maternal omeprazole
doses of 20 mg daily produce low levels in milk and would not be expected to
cause any adverse effects in breastfed infants. |
·
Omeprazole is present in breast milk. ·
The relative infant dose (RID) of omeprazole is 0.2% to 0.43% when
calculated using the highest average breast milk concentration located and
compared to an infant therapeutic dose of 0.7 to 1.5 mg/kg/day.* ·
The RID of omeprazole was calculated using the highest average milk
concentration located (20.03 mcg/L), providing an estimated daily infant dose
via breast milk of 0.003 mg/kg/day. This milk concentration was obtained following
maternal chronic administration of oral omeprazole 20 mg/day; the peak breast
milk concentration occurred 3 hours after the dose (Marshall 1998). ·
No adverse effects were noted in one infant exposed to omeprazole
following maternal administration of oral omeprazole 20 mg/day for 3 months;
the authors of this case report noted that the acidic content of a breastfed
infants' stomach may potentially inactivate any ingested omeprazole (Marshall
1998). ·
According to the manufacturer, the decision to continue or
discontinue breastfeeding during therapy should take into account the risk of
infant exposure, the benefits of breastfeeding to the infant, and benefits of
treatment to the mother. |
Limited Human Data—Potential Toxicity ·
Only one report describing the use of omeprazole during human
lactation has been located. A woman with refractory GERD was treated with
omeprazole (20 mg/day) for 7–8 weeks before delivering a
premature male infant (birth weight not given) at 36 weeks’ gestation.
Treatment was continued during breastfeeding. During this time, she fed her
infant son just before taking her dose at 8 AM, refrained from nursing for 4
hours, then expressed and discarded her milk at 12 noon. At 3 weeks
postpartum, blood and milk samples were obtained at 8 AM and then every 30
minutes for 4 hours (i.e., until 12 noon). The milk was obtained by
expressing but the volume of the samples was not specified. Maternal serum
concentrations began to rise 90 minutes after the dose, reached 950 nM at 12
noon, and appeared to be still rising. Breast milk levels also began to rise
at 90 minutes and peaked at 180 minutes at 58 nM. The infant was doing well
at 1 year of age (13). ·
The above case report estimated a maximum daily omeprazole exposure
of 4 mcg, but the calculation was based on a consumption of only 200 mL of
milk/day for a 5-kg infant (40 mL/kg/day). A more acceptable value is 150
mL/kg/day (34). Moreover, the milk samples were obtained by expression and the
volumes expressed were not given. This is clinically relevant because
hindmilk obtained at the end of a feeding is 4–5 times higher in fat than foremilk (35). For
lipid-soluble drugs, such as omeprazole, hindmilk would be expected to
contain most of the drug in milk. ·
In concurrence with the above case report, the molecular weight of omeprazole
(about 345) suggests that it will be excreted into human milk. One source
stated that the safety of a drug during breastfeeding can be arbitrarily defined
as no more than 10% of the adult dose standardized by weight if a therapeutic
dose for infants is not known (34). ·
Until additional studies show that omeprazole meets this criterion,
the use of omeprazole during breastfeeding should probably be avoided. Other
concerns, such as the carcinogenicity observed in animals and the potential
for suppression of gastric acid secretion in the nursing infant, also warrant
further study. |
|
Esomeprazole |
Esomeprazole is the S-enantiomer of the proton-pump
inhibitor, omeprazole. Limited information indicates that maternal doses of
10 mg daily produce low levels in milk and would not be expected to cause any
adverse effects in breastfed infants. |
·
Esomeprazole is present in breast milk (Saito 2020). ·
A case report describes maternal use of esomeprazole 10 mg/day
throughout pregnancy and postpartum. Breast milk was sampled multiple times
between 2 and 4 days after delivery at term. The highest breast milk
concentration was 4 hours after the maternal dose (19.6 ng/mL) and
esomeprazole was no longer detected in breast milk 10 hours after the maternal
dose. Using the highest breast milk concentration, authors of the study
determined the estimated daily infant dose via breast milk to be 0.003
mg/kg/day. This infant received >50% of nutrition via breast milk and was
developing normally as of 6 months of age (Saito 2020). ·
According to the manufacturer, the decision to breastfeed during
therapy should consider the risk of infant exposure, the benefits of
breastfeeding to the infant, and the benefits of treatment to the mother. |
No Human Data - Potential Toxicity · No reports describing the
use of esomeprazole, the S-isomer of omeprazole, during human lactation have been located. · The molecular weight (about
345 for the anhydrous free base) is low enough that excretion into breast
milk should be expected. · The effect of esomeprazole
on a nursing infant is unknown. The potential for toxic effects such as those
seen in adults (e.g., headache, diarrhea, and abdominal pain) and the
suppression of gastric acid secretion are a concern, as is the potential for
the gastric tumors that have been observed in animals after long-term use. · Small amounts of
omeprazole, a mixture of the S- and R-isomers, are excreted into milk, but
the quantity excreted needs further clarification. (See Omeprazole.) · If a lactating womass condition
requires esomeprazole, consideration of the drug’s properties might allow her
to nurse without significantly exposing her infant. ·
Esomeprazole is dosed once daily because the inhibition of gastric
acid secretion is prolonged. In contrast, the plasma elimination half-life is
short (about 1–1.5 hours). Thus, waiting 5–7.5 hours after a dose should eliminate up to 97%
of the drug from the plasma. Moreover, the mean peak plasma concentration is
reported to occur 1.6 hours after the dose, and waiting 5-7.5 hours would
avoid the period when the greatest amount of drug is available to enter milk.
Emptying both breasts near the end of the waiting period and discarding the
milk completes the strategy to limit the infant’s exposure. This strategy was
used in one case involving omeprazole but warrants further study. |
|
Amoxicillin |
Limited information indicates that amoxicillin produces low
levels in milk that are not expected to cause adverse effects in breastfed
infants. Occasionally, rash and disruption of the infant's gastrointestinal
flora, resulting in diarrhea or thrush, have been reported, but these effects
have not been adequately evaluated. Amoxicillin is acceptable in nursing
mothers. Amoxicillin powder for suspension reconstituted with breastmilk is
absorbed as well as the powder reconstituted with water. |
·
Amoxicillin is present in breast milk (Kafetzis 1981). ·
The relative infant dose (RID) of amoxicillin is 0.15% to 0.54% when
calculated using the highest average breast milk concentration located and
compared to an infant therapeutic dose of 25 to 90 mg/kg/day.* ·
The RID of amoxicillin was calculated using a milk concentration of
0.9 mcg/mL, providing an estimated daily infant dose via breast milk of 0.135
mg/kg/day. This milk concentration was obtained following maternal
administration of a single oral dose of amoxicillin 1,000 mg (Kafetzis 1981). ·
Self-limiting diarrhea, rash, and somnolence have been reported in
nursing infants exposed to amoxicillin (Benyamini 2005; Goldstein 2009; Ito
1993); the manufacturer warns of the potential for allergic sensitization in
the infant. In general, antibiotics that are present in breast milk may cause
non-dose-related modification of bowel flora. Monitor infants for GI
disturbances, such as thrush or diarrhea (WHO 2002). ·
Although the manufacturer recommends that caution be exercised when
administering amoxicillin to breastfeeding women, amoxicillin is considered
compatible with breastfeeding when used in usual recommended doses (WHO
2002). ·
Amoxicillin may be used to treat mastitis in breastfeeding women. The
treatment of mastitis with antibiotics is generally not considered unless
symptoms do not improve with conservative management or the woman is acutely
ill. When antibiotics are clinically indicated for treatment, amoxicillin is
one of the suggested therapies for gram-negative organisms (WHO 2000). ·
Recommendations for using amoxicillin for the treatment of B.
anthracis in breastfeeding women are the same as in pregnancy.
Exposure to anthrax is not considered a contraindication to breastfeeding.
However, if there are active cutaneous lesions on the breast, contact with
the infant should be avoided and feeding from the affected breast should not
occur until >48 hours of appropriate antibiotic therapy (Meaney-Delman
2014). |
·
Amoxicillin is excreted into breast milk
in low concentrations. Following a 1-g oral dose given to six mothers, peak
milk levels occurred at 4–5 hours, averaging
0.9 mcg/mL (range 0.68–1.3 mcg/mL) (15).
Mean milk:plasma ratios at 1, 2, and 3 hours were 0.014, 0.013, and 0.043,
respectively. Although no adverse effects have been observed, three potential
problems exist for the nursing infant: modification of bowel flora, direct
effects on the infant (e.g., allergy or sensitization), and interference with
the interpretation of culture results if a fever workup is required. ·
In a 1993 cohort study, diarrhea was
reported in 32 (19.3%) nursing infants of 166 breastfeeding mothers who were
taking antibiotics (16). For the 25 women taking amoxicillin, diarrhea was observed
in 3 (12%) infants. The diarrhea was considered minor because it did not
require medical attention. ·
The American Academy of Pediatrics
(2001) classifies amoxicillin as compatible
with breastfeeding. |
|
Clarithromycin |
Because of the low levels of clarithromycin in breastmilk
and safe administration directly to infants, it is acceptable in nursing
mothers. The small amounts in milk are unlikely to cause adverse effects in
the infant. Monitor the infant for possible effects on the gastrointestinal
flora, such as diarrhea, candidiasis (thrush, diaper rash). Unconfirmed
epidemiologic evidence indicates that the risk of infantile hypertrophic
pyloric stenosis might be increased by maternal use of macrolide antibiotics
during the first two weeks of breastfeeding, but others have questioned this
relationship. |
·
Clarithromycin and its active metabolite (14-hydroxy clarithromycin)
are present in breast milk. ·
The relative infant dose (RID) of clarithromycin is <1% when
calculated using the highest mean breast milk concentration located and
compared to an infant therapeutic dose of 15 mg/kg/day.* ·
Using the highest mean milk concentrations (clarithromycin: 0.85
mg/L; 14-hydroxy clarithromycin: 0.63 mg/L), the estimated daily infant dose
via breast milk was calculated to be 136 mcg/kg/day. This milk concentration
was obtained following maternal administration of oral clarithromycin 250 mg
twice daily; the half-lives of clarithromycin and 14-hydroxy clarithromycin
in breast milk were 4.3 ± 0.3 hours and 9 ± 1.2 hours, respectively (Sedlmayr
1993). ·
Decreased appetite, diarrhea, rash, and somnolence have been reported
in breastfed infants exposed to macrolide antibiotics (Goldstein 2009). In
general, antibiotics that are present in breast milk may cause
non-dose-related modification of bowel flora. Monitor infants for GI
disturbances, such as thrush and diarrhea (WHO 2002). In addition, an
increased risk for infantile hypertrophic pyloric stenosis (IHPS) may be
present in infants who are exposed to macrolides via breast milk, especially
during the first two weeks of life (Lund 2014); however, data are conflicting
(Goldstein 2009). According to the manufacturer, the decision to breastfeed
during therapy should consider the risk of infant exposure, the benefits of
breastfeeding to the infant, and benefits of treatment to the mother. |
Compatible ·
Clarithromycin is excreted into breast milk. In a 1993 study, 12
mothers were given clarithromycin 250 mg twice daily. Both the parent drug
and metabolite were excreted into milk, with peaks levels measured at 2.2 and
2.8 hours, respectively, The half-lives of the drug and metabolite were 4.3
and 9 hours, respectively. The combined exposure for an exclusively breastfed
infant was about 2% of the mother’s weight-adjusted dose. ·
A 2003 study investigated the association between maternal use of
macrolides and infantile hypertrophic pyloric stenosis (11). The Danish
population-based cohort study comprised 1166 women who had a prescribed
macrolide (azithromycin, clarithromycin, erythromycin, spiramycin, or
roxithromycin) from birth to 90 days postnatally compared with up to 41,778
controls. The OR for stenosis was 2.3–3.0, depending on the postnatal period of exposure
(42, 56, 70, or 90 days), but none of the ORs was significant. ·
When stratified by gender, the ORs for males were 1.8–3.1 and again were not statistically significant.
For females, the ORs at 70 and 90 days postbirth were 10.3 and 7.5, but only
the former was significant (95% CI 1.2–92.3) (11). ·
Investigators from Israel examined the possible association between
macrolide (azithromycin, clarithromycin, erythromycin, or roxithromycin)
exposure in milk and infantile hypertrophic pyloric stenosis in a 2009 study
(13). ·
They compared 55 infants exposed to a macrolide antibiotic to 36
infants exposed to amoxicillin. In the macrolide group, 7 (12.7%) had an
adverse reaction (rash, diarrhea, loss of appetite, somnolence), whereas 3
infants (8.3%) in the amoxicillin group had an adverse reaction (rashes,
somnolence). ·
The rates of adverse reactions were comparable. No cases of infantile
hypertrophic pyloric stenosis were observed. |
|
Metronidazole |
Because of the
well demonstrated genotoxicity and mutagenicity in bacteria, carcinogenicity
in animals, and possible mutagenicity in humans, concern has been raised
about exposure of healthy infants to metronidazole via breastmilk. The
relevance of these findings has been questioned and no definitive study has
yet been performed in humans. Opinions vary
among experts on the advisability of using metronidazole during longer-term
therapy while breastfeeding, but some sources recommend discontinuing
breastfeeding for 12 to 24 hours after single-dose maternal treatment. Other
drugs are available for some conditions that metronidazole is used to treat.
Topical or vaginal use of metronidazole during breastfeeding is unlikely to
be of concern, although the manufacturer of one vaginal product recommends
not breastfeeding during treatment and for 2 days after the last dose. |
·
Metronidazole and its active hydroxyl metabolite are present in
breast milk at concentrations similar to maternal plasma concentrations. ·
The relative infant dose (RID) of metronidazole is 13.7% to 22.9%
when calculated using the highest average breast milk concentration reported
and compared to an oral infant therapeutic dose of 30 to 50 mg/kg/day. * ·
Using the highest average milk concentration (45.8 mcg/mL), the
estimated daily infant dose via breast milk is 6.87 mg/kg/day. This milk
concentration was obtained following a single maternal dose of oral metronidazole
2,000 mg; the authors estimated the infant would have been exposed to
metronidazole 21.8 mg over the first 24 hours after the dose (Erickson 1981). ·
The highest average milk concentration occurred 2 to 4 hours after a
single oral maternal dose; the half-life in breast milk was ~9 to 10 hours
(Erickson 1981). Metronidazole and its active metabolite can be detected in
the serum of breastfeeding infants (Gray 1961; Heisterberg 1983; Passmore
1988). ·
Loose stools, oral and perianal Candida growth, and
oral thrush have been reported in breastfeeding infants exposed to
metronidazole (Passmore 1988) ·
The manufacturer warns of the risk of carcinogenicity in patients
exposed to metronidazole based on animal studies; theoretically, this risk is
also present in breastfeeding infants exposed to metronidazole via breast
milk. Therefore, the manufacturer recommends a decision be made whether to
discontinue breastfeeding or to discontinue the drug, taking into account the
importance of treatment to the mother. Some guidelines note if metronidazole
is given, breastfeeding should be withheld for 12 to 24 hours after a single
dose (CDC [Workowski 2015]; WHO 2002); alternatively, the mother may pump and
discard breast milk for 24 hours after taking the last metronidazole dose.
Breastfeeding should be avoided in women requiring treatment with
metronidazole for inflammatory bowel disease (van der Woude 2015). Use of
other agents is preferred when treating breastfeeding women for Clostridioides (formerly Clostridium) difficile infection
(Surawicz 2013). |
§ Hold Breastfeeding (Single Dose) § Limited Human Data—Potential
Toxicity (Divided Dose) ·
Metronidazole is excreted into breast milk. ·
Following a single 2-g oral dose in three patients, peak milk
concentrations in the 50–60 mcg/mL range were
measured at 2–4 hours (52). With normal
breastfeeding, infants would have received about 25 mg of metronidazole
during the next 48 hours. By interrupting feedings for 12 hours, infant
exposure to the drug would have been reduced to 9.8 mg, or 3.5 mg if feeding
had been stopped for 24 hours (52). ·
In women treated with divided oral doses of either 600 or 1200
mg/day, the mean milk levels were 5.7 and 14.4 mcg/mL, respectively (53). The
milk:plasma ratios in both groups were approximately 1.0. The mean plasma
concentra-tions in the exposed infants were about 20% of the maternal plasma
drug level. Eight women treated with metronidazole rectal suppositories, 1 g
every 8 hours, produced a mean milk drug level of 10 mcg/mL with maximum
concentrations of 25 mcg/mL (54). ·
One report described diarrhea and secondary lactose intolerance in a
breastfed infant whose mother was receiving metronidazole (55). The
relationship between the drug and the events is unknown. Except for this one
case, no reports of adverse effects in metronidazole-exposed nursing infants
have been located. However, because the drug is mutagenic and
carcinogenic in some test species (see
Fetal Risk Summary), unnecessary exposure to metronidazole should be avoided.
·
However, topical or vaginal use of metronidazole during breastfeeding
does not appear to represent a risk to a nursing infant. ·
A 1988 report analyzed the milk and plasma concentrations of
metronidazole and its metabolite (hydroxymetronidazole) in 12 breastfeeding
women who had been taking 400 mg 3 times daily for 4 days (56). The mean
milk:plasma ratios for the parent drug and metabolite were 0.9 and 0.76,
respectively. In seven of the nursing infants, the plasma concentra-tions for
the parent drug and metabolite ranged from 1.27 to 2.41 mcg/mL and 1.1 to 2.4 |
|
Levofloxacin |
Levofloxacin is the S-enantiomer of the
fluoroquinolone, ofloxacin. No information is available on the clinical use
of levofloxacin during breastfeeding. However, amounts in breastmilk appear
to be low and would not be expected to cause any adverse effects in breastfed
infants. Fluoroquinolones such as levofloxacin have traditionally not been
used in infants because of concern about adverse effects on the infants'
developing joints. However, recent studies indicate little risk.[1][2] The
calcium in milk might prevent absorption of the small amounts of
fluoroquinolones in milk,[3] but insufficient data exist to prove or disprove
this assertion. Use of levofloxacin is acceptable in nursing mothers with
monitoring of the infant for possible effects on the gastrointestinal flora,
such as diarrhea or candidiasis (thrush, diaper rash). Avoiding breastfeeding
for 4 to 6 hours after a dose should decrease the exposure of the infant to
levofloxacin in breastmilk. Maternal use of an eye drop that contains
levofloxacin presents negligible risk for the nursing infant. |
·
Levofloxacin is present in breast milk. ·
The relative infant dose (RID) of levofloxacin is 6% when calculated
using the highest breast milk concentration located and compared to a
therapeutic infant dose of 20 mg/kg/day. * ·
The RID of levofloxacin was calculated using a milk concentration of
8.2 mcg/mL, providing an estimated daily infant dose via breast milk of 1.23
mg/day. This milk concentration was based on random samples obtained
following a maternal dose of IV levofloxacin 500 mg/day for 9 days, followed
by oral therapy for a total of 23 days beginning 3 days postpartum; the
half-life in the breast milk was ~7 hours (Cahill 2005). ·
Levofloxacin may be considered for use in breastfeeding patients
requiring antibiotics for inhalational anthrax (postexposure); according to
the manufacturer, the decision to breastfeed during therapy should consider
the risk of infant exposure, the benefits of breastfeeding to the infant, and
the benefits of treatment to the mother. However, patients with active
cutaneous anthrax lesions on the breast should avoid direct infant contact;
feeding from the affected breast should be avoided until 48 hours after the
appropriate antibiotic therapy (Meaney-Delman 2014). ·
For other indications, the manufacturer does not recommend use of
levofloxacin in breastfeeding patients during therapy or for 2 days after the
last levofloxacin dose due to concerns of potential serious adverse
reactions; alternatively, lactating patients can pump and discard breast milk
during therapy and for 2 days after the last levofloxacin dose. The risk of
articular damage in breastfed infants exposed to other quinolones (ie,
ciprofloxacin) is considered low even in children receiving high therapeutic
doses. Therefore, some sources do not consider maternal use of these agents
to be a reason to discontinue breastfeeding as long as the infant is
monitored for GI symptoms (eg, diarrhea) that could occur following antibiotic
exposure (Kaplan 2015). Other sources recommend avoiding quinolone
antibiotics if alternative agents are available (WHO 2002). ·
In general, antibiotics that are present in breast milk may cause
nondose-related modification of bowel flora. Monitor infants for GI
disturbances (WHO 2002). |
Limited Human Data—Probably Compatible ·
When first marketed, the use of levofloxacin during lactation was not
recommended because of the potential for arthropathy and other serious toxicity
in the nursing infant. ·
Phototoxicity has been observed with quinolones when exposure to
excessive sunlight (i.e., ultraviolet [UV] light) has occurred.
Well-differentiated squamous cell carcinomas of the skin has been produced in
mice who were exposed chronically to some fluoroquinolones and periodic UV
light (e.g., see Lomefloxacin), but studies to evaluate the carcinogenicity
of ofloxacin in this manner have not been conducted. ·
Levofloxacin is excreted into breast milk. A lactating woman received
levofloxacin 500 mg/day during the first 23 days postpartum. Milk samples were
collected at various times at steady state. ·
The peak concentration in milk, 8.2 mcg/mL, occurred 5 hours after a
dose. The pharmaco-kinetics in milk was similar to those in the plasma.
Minimal levels of the drug were detectable 65 hours after the last dose. The infant was not allowed to breastfeed. The effect of this exposure on a nursing infant is unknown, but other
fluoroquinolones are classified as compatible with breastfeeding by the American
Academy of Pediatrics (see Ofloxacin and Ciprofloxacin). |
|
Doxycycline |
A number of reviews have stated that tetracyclines are
contraindicated during breast feeding because of possible staining of
infants’ dental enamel or bone deposition of tetracyclines. However, a close
examination of available literature indicates that there is not likely to be
harm in short-term use of doxycycline during lactation because milk levels
are low and absorption by the infant is inhibited by the calcium in
breastmilk. Doxycycline use in children <8 years is now considered
acceptable in courses up to 21 days. As a theoretical precaution, avoid
prolonged (>21 days) or repeat courses during nursing. Monitor the infant
for rash and for possible effects on the gastrointestinal flora, such as diarrhea
or candidiasis (thrush, diaper rash). |
·
Doxycycline is present in breast milk. ·
The relative infant dose (RID) of doxycycline is 6.14% when
calculated using the highest average breast milk concentration located and
compared to an infant therapeutic dose of 4.4 mg/kg/day.* ·
Using the highest average milk concentration (1.8 mcg/mL), the
estimated daily infant dose via breast milk is 0.27 mg/kg/day. This milk
concentration was obtained following maternal administration of a single oral
dose of doxycycline 200 mg (Tokuda 1969). Concentrations of doxycycline in
breast milk may increase with duration of therapy (Anderson 1991). ·
Oral absorption of doxycycline is not markedly influenced by
simultaneous ingestion of milk; therefore, oral absorption of doxycycline by
the breastfeeding infant would not be expected to be diminished by the
calcium in the maternal milk. ·
The therapeutic use of doxycycline should be avoided during tooth
development (children <8 years) unless there are no alternative therapies
due to the potential for tissue hyperpigmentation, tooth enamel hypoplasia,
or permanent tooth discoloration. Theoretically, this risk is also present in
breastfeeding infants exposed to doxycycline via breast milk. Although
breastfeeding is not specifically contraindicated, the effects of long-term
exposure via breast milk are not known. According to the manufacturer, the
decision to continue or discontinue breastfeeding during therapy should take
into account the risk of infant exposure, the benefits of breastfeeding to the
infant, and benefits of treatment to the mother. The World Health
Organization (WHO) states that maternal use of doxycycline should be avoided
if possible but that a single dose or the short-term use of doxycycline is
probably safe; there exists a possibility of dental staining and inhibition
of bone growth in the infant, especially with prolonged use (WHO 2002). In
general, antibiotics that are present in breast milk may cause
nondose-related modification of bowel flora. Monitor infants for GI disturbances,
such as thrush and diarrhea (WHO 2002). ·
Current guidelines note that the short-term use of doxycycline for
the treatment of RMSF (rocky mountain spotted fever) is considered compatible
with breastfeeding (CDC [Biggs 2016]). If used for the treatment or prophylaxis
of malaria, breastfeeding during doxycycline therapy is considered
compatible; however, the theoretical risk of dental staining and inhibition
of long bone growth in the breastfeeding infant should be considered (WHO
2002). Breastfeeding is not recommended when doxycycline is being used for
maternal treatment of acne (AAD [Zaenglein 2016]). |
Compatible ·
Doxycycline is excreted into breast milk. ·
Oral doxycycline, 200 mg, followed after 24 hours by 100 mg, was
given to 15 nursing mothers. Milk:plasma ratios determined at 3 and 24 hours
after the second dose were 0.3 and 0.4, respectively. Mean milk
concentrations were 0.77 and 0.38 mcg/mL. ·
Theoretically, dental staining and inhibition of bone growth could
occur in breastfed infants whose mothers were consuming doxycycline. However,
this theoretical possibility seems remote, because in infants exposed to a
closely related antibiotic, tetracycline, serum levels were undetectable
(less than 0.05 mcg/mL). ·
The American Academy of Pediatrics classifies tetracycline as compatible with breastfeeding. Three
potential problems may exist for the nursing infant even though there are no
reports in this regard: modification of bowel flora, direct effects on the
infant, and interference with the interpretation of culture results if a
fever workup is required. |
|
Bismuth subsalicylate |
Because of the possibility of absorption of salicylate from
the breastmilk by the infant, alternatives are preferred. |
·
Salicylates enter breast milk (Bar-Oz 2004). Following ingestion of bismuth
subsalicylate, plasma salicylate concentrations may be comparable to those
following ingestion of aspirin (Bierer 1990). Refer to the aspirin monograph
for additional information related to salicylates and breastfeeding. ·
It is not known if bismuth is present in breast milk; however,
absorption is limited following oral admini-stration of this preparation at
usual doses (Bierer 1990). ·
A case report describes bowel obstruction in a breastfed infant whose
mother applied a bismuth-containing ointment to her nipples prior to
breastfeeding (Ingestion of bismuth-containing 1974). ·
Bismuth subsalicylate should not be used for the treatment or
prevention of traveler’s diarrhea in breastfeeding patients (CDC 2018). Under à Uptodate: Aspirin: Drug
Information ü The WHO considers
occasional doses of aspirin to be compatible with breastfeeding but
recommends avoiding long-term therapy and consider monitoring the infant for
adverse effects (hemolysis, prolonged bleeding, metabolic acidosis) (WHO
2002). ü Other sources also suggest
avoiding high doses of aspirin while breastfeeding due to the theoretical
risk of Reye syndrome (Bar-Oz 2003; Spigset 2000). |
No Human Data—Potential Toxicity ·
The excretion of significant amounts of
bismuth obtained from bismuth subsalicylate into breast milk is not expected
because of the poor absorption of bismuth into the systemic circulation. ·
Salicylates, however, are excreted in
milk and are eliminated more slowly from milk than from plasma with
milk:plasma ratios rising from 0.03 to 0.08 at 3 hours to 0.34 at 12 hours
(12). ·
Because of the potential for adverse
effects in the nursing infant, the American
Academy of Pediatrics recommends that salicylates should be used cautiously
during breastfeeding (13). ·
A review stated that bismuth subsalicylate
should be avoided during lactation
because of systemic salicylate absorption (14). |
*RID
= In general, breastfeeding is considered acceptable
when the RID is <10%; when an RID is >25% breastfeeding should generally
be avoided (Anderson 2016; Ito 2000).
*Author’s Comment: Suggest to find entries in the
latest edition of Briggs – especially for PPI.
Extra Note:
|
Metronidazole –
is it safe to use with breastfeeding?
Vanessa Chapman, Director, Trent Medicines Information Service & UK Drugs in Lactation Advisory Service · Published 12 October 2020 |
·
The balance of current evidence and clinical experience,
and the consensus of specialist opinion, is that there is no established
mutagenic or carcinogenic risk to infants breastfeeding from mothers
receiving routine short-course treatment with metronidazole by any route. ·
Low-dose oral metronidazole, 200-400 mg three times
daily, produces milk levels only slightly lower than corresponding levels in
maternal plasma (76 to 99%). However,
doses up to 500 mg three times daily for a 7 to 10 day course are considered
to be compatible with breastfeeding. ·
Single, 2 g high-dose oral metronidazole produces
significantly higher levels in milk than low-dose oral therapy. However, the
estimated total ingestion is still lower than the daily infant dose given
directly. Daily 2 g oral doses, normally given for 3 days, are considered to
be compatible with breastfeeding. ·
Intravenous administration produces similar maternal
plasma and milk levels to equivalent oral doses, although the data are
limited. Short-course IV metronidazole is considered to be compatible with
breastfeeding. ·
Administration of metronidazole by rectal, vaginal,
or topical routes produces significantly lower plasma levels, and would
therefore be expected to produce correspondingly lower milk levels than after
oral administration, and is considered to be compatible with breastfeeding. ·
Adverse effects in breastfed infants whose mothers
have been treated with metronidazole are rare and unsubstantiated, and
include loose stools, candidiasis and lactose intolerance. ·
Anecdotal reports of infants rejecting milk at the
start of feeds may be due to a metallic/bitter taste imparted to foremilk by
a water soluble metabolite, although this again has not been substantiated. ·
If an infant is exposed to metronidazole via breast
feeding they may experience alteration of the oral and gut flora, therefore
monitor the infant for oral candida infections and The infant should also be
monitored for rash due to the theoretical concern of hypersensitivity. ·
The concentrations of metronidazole seen in breast
milk are too low to have a bactericidal effect in the infant; therefore an
infant with an active infection needs independently treating in their own
right. ·
There are no data relating to the effects of
metronidazole exposure in preterm breastfed infants. Special consideration
should be given to the use of metronidazole by any route in preterm or
low-birth-weight infants, or in infants with compromised renal or hepatic
function. |
UptoDate: Treatment regimens for Helicobacter pylori |
TREATMENT DURING
PREGNANCY AND LACTATION When peptic
ulcer disease is diagnosed in a woman who is pregnant, the mainstay of
treatment is typically acid suppression. If H. pylori is
present, treatment is typically deferred until after delivery. However, with
the exception of bismuth, fluoroquinolones, and tetracycline,
the other medications used for H. pylori eradication are low
risk in pregnancy, especially after 14 weeks. This includes clarithromycin, amoxicillin,
and probably metronidazole.
Moreover, there is some evidence that H. pylori can cause
severe nausea and vomiting in pregnancy, including hyperemesis gravidarum [66,67].
Thus, if indicated, H. pylori treatment should be considered
in pregnancy. Some of
the medications typically used for the treatment of H. pylori are
possibly unsafe for nursing infants (eg, bismuth, metronidazole, levofloxacin). |
|
Treatment of Helicobacter pylori infection in adults (Conseil National Professionnel
d’Hépato-Gastroentérologie, France ; May 2017) |
Treatment is
not urgent: in case of pregnancy or breastfeeding, the treatment must be
deferred. |
|
Treatment of Helicobacter pylori in
Special Patient Populations (by Andrea
Richard, Minnesota Direct Care
and Treatment, 2020) |
·
In asymptomatic patients who are pregnant or breastfeeding, it is
recommended to delay treatment until delivery or cessation of breastfeeding
due to lack of safety data for any of the regimens. ·
In symptomatic patients, such as those with hyperemesis gravidarum, a
risk vs. benefit conversation with the patient must occur. ·
If the decision to pursue treatment is made, clarithromycin triple
therapy is recommended. https://www.pharmacy.umn.edu/degrees-and-programs/postgraduate-pharmacy-residency-program/news-events-and-publications/curbside-consult-volume-17-issue-4-fourth-quarter-2019/treatment-helicobacter-pylori-special-patient-populations |
