Drugs in Pregnancy

Detail-Document #250607
−This Detail-Document accompanies the related article published in−

PHARMACIST’S LETTER / PRESCRIBER’S LETTER
June 2009 ~ Volume 25 ~ Number 250607
Antibiotic and Antifungal Use During Pregnancy and Breastfeeding

Infections such as urinary tract infection, yeast infection, or upper respiratory infection are not uncommon in pregnant or lactating women. A list of
antibiotics/antifungals and their safety profiles when used during pregnancy and lactation are included in the chart below. Overall, the rule of thumb is to avoid drug
use during the 1st trimester and choose an older agent with the most fetal data indicating the drug is safe and effective. Keep in mind that all drugs carry some risk
during pregnancy. It is important to weigh the risks and benefits before recommending drug use during pregnancy. Additional fetal monitoring may be
warranted if exposure to agents of uncertain teratogenic potential has occurred.37 When an antibiotic is used during lactation, regardless of concentration excreted
into breast milk, potential problems for the nursing infant include 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 work up is required.1 Keep in mind that antibiotic dosage may need to be adjusted due to the different
volume of distribution in pregnant women during different gestation periods when treating a systemic infection.2,11 Please proceed to the end of this document for a
list of helpful on-line resources concerning drug use in pregnancy.
Abbreviation: AAP=American Academy of Pediatrics; BSA=body surface area; GI=gastrointestinal; IV=intravenous.

Drug Pregnancy Use in Pregnancy Use in Lactation
Categorya
Amikacin D • See aminoglycosides. • See aminoglycosides
• Studies in patients undergoing elective abortions in the 1st and • Amikacin is excreted into breast milk
2nd trimesters indicate that amikacin distributes to most fetal in low concentrations. 1
1
tissues except the brain and cerebrospinal fluid. • Ototoxicity not expected in infant
• There are no known reports linking the use of amikacin to since oral absorption of amikacin is
congenital defects.1 low.1
Aminoglycosides D • In a large database review, a total of 38 cases and 42 controls • Ototoxicity not expected in infant
were treated with aminoglycosides. The investigators since oral absorption of
concluded that there was no detectable teratogenic risk for aminoglycosides is low.1
structural defects for any of the aminoglycoside antibiotics.1 • U.S./Canadian product labeling
• There is a theoretical risk of vestibular and auditory dysfunction recommend against use during
associated with aminoglycoside use.9 However, ototoxicity or breastfeeding.
nephrotoxicity have not been reported (see exceptions below) as
an effect of in utero exposure.1,2
• Eighth cranial nerve toxicity in the human fetus is well known
after exposure to certain aminoglycosides (see kanamycin and
streptomycin), and all aminoglycosides could potentially cause
this.1
More. . .
Copyright © 2009 by Therapeutic Research Center
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249
www.pharmacistsletter.com ~ www.prescribersletter.com
(Detail-Document #250607: Page 2 of 27)

Categorya
Amoxicillin B • See penicillin derivatives. • Excreted into breast milk in low
• Amoxicillin has been used as a single 3 g dose for treatment of concentrations.1,2
bacteriuria in pregnancy without causing fetal harm.1 • AAP classifies amoxicillin as
compatible with breastfeeding.3
Amphotericin B B • There are no reports linking the use of amphotericin B with • No human data.
(Abelcet, etc) congenital defects.1 • U.S./Canadian product labeling
• Amphotericin B crosses the placenta to the fetus.1 recommends against use of drug while
• In a large database review, none of the nine 1st trimester breastfeeding.
exposures to amphotericin B showed evidence of adverse fetal
effects.1
• Amphotericin can be used during pregnancy in patients who will
clearly benefit from the drug.1
• Evaluate neonate for renal dysfunction & hypokalemia if mother
on chronic amphotericin B at delivery.37
Ampicillin B • See penicillin derivatives. • Excreted into breast milk in low

• In a large database review, of the 10,011 1st trimester exposures concentrations.1
to ampicillin, there was a total of 441 (4.4%) major birth defects
observed (426 expected). However these data do not support an
association between the drug and the defects.1
Anidulafungin C • No human data; animal data suggest low risk.1 • No human data.
(Eraxis) • It is best to avoid anidulafungin in pregnancy since there are no • The effects on a nursing infant are
human pregnancy data. However, if the woman’s condition unknown, but dose-related histamine-
requires it, the benefit probably outweighs the unknown risk.1 mediated symptoms (rash, urticaria,
• If the decision is made to use anidulafungin, the lowest flushing, pruritus, dyspnea, and
effective dose should be used.1 hypotension) have been observed in
• Per IDSA, use with caution during pregnancy.36 Use not adults receiving IV anidulafungin.1
recommended per CDC.37
Azithromycin B • Limited human data; animal data suggest low risk.1 • Limited human data.
(Zithromax [U.S.]; generics • Animal studies using mice and rats treated with doses up to • Accumulates in breast milk.
[Canada]) maternal toxic levels showed no impairment of fertility or harm • Likely compatible with breastfeeding.1
to the fetus.1
More. . .

Categorya
Azole antifungals (Topical) Refer to • Prospective and observational studies involving the use of • See individual agents.
individual topical antifungals did not show an increased risk of major
(See individual agents) agents malformations with exposure during pregnancy anytime.8 (No
human data for topical ketoconazole).1
• Topical (vaginal) use of azole antifungals (e.g., clotrimazole,
miconazole, terconazole, etc) are considered therapy of choice
to treat vaginal yeast infection during pregnancy.19,20
• Topical (vaginal) azole therapy should be recommended for 7
days instead of a shorter duration for vaginal yeast infections
because of improved treatment success.19,20
Aztreonam B • No human data; animal data suggest low risk.1 • Limited human data.
(Azactam) • Animal studies with pregnant rats and rabbits administered high • Excreted into breast milk.1
IV doses at 15 times the maximum recommended human dose • The AAP classifies aztreonam as
(U.S. only) and five times the maximum recommended human dose, compatible with breastfeeding.3
respectively, did not produce embryotoxic, fetotoxic, or • Product labeling recommends not
teratogenic effects.1 breastfeeding during treatment.
Capreomycin C • No human data. • No human data.
(Capastat) • Similar toxicity concerns as that of aminoglycosides (e.g., • Less than 1% is absorbed from an oral
cranial nerve VIII and renal).1 dose by the mother; therefore the risk,
(U.S. only) • Two sources state that capreomycin should be avoided during if any, to a nursing infant appears to
pregnancy due to potential of ototoxicity and deafness. Neither be minimal.1
source cited pregnancy data involving capreomycin.1 (Black
Box Warning indicates safety in pregnancy unknown.)28
Caspofungin C • No human data; animal data suggest risk especially if exposure • No human data.
(Cancidas) is during 1st trimester.1 • The risk of harm from exposure to
• If indicated, maternal treatment should avoid the 1st trimester if caspofungin appears to be low.
possible.1 • Monitor infants for signs and
• Per IDSA, use with caution during pregnancy.36 symptoms of histamine release (e.g.,
rash, facial swelling, pruritus, etc) and
GI complaints.
Cefadroxil B • See cephalosporins. • Excreted into breast milk in low

(Duricef [U.S.]; generics • In a large database review of the 722 exposures to cefadroxil concentrations.1
[Canada]) during the 1st trimester, a total of 27 major birth defects were • AAP classifies cefadroxil as
observed (30 expected). However, these data do not support an compatible with breastfeeding.3
association between the drug and congenital defects.1
More. . .

Categorya
Cephalosporins B • Cephalosporins as a class do not appear to cause fetal toxicity • AAP classifies many cephalosporin
and are usually considered safe to use during pregnancy.1 drugs as compatible with
• See individual drugs for more information. breastfeeding.3
• See individual drugs for more
information.
Cefazolin B • See cephalosporins. • Excreted into breast milk in low

(Ancef [U.S.], Kefzol • Cefazolin 2 g IV every 8 hours has been used in the treatment of concentrations.1
[U.S.]; generics [Canada]) pyelonephritis occurring in the second half of pregnancy. No • The AAP classifies cefazolin as
adverse fetal outcomes attributable to cefazolin was observed.1 compatible with breastfeeding.3
Cefdinir B • See cephalosporins. • Cefdinir is expected to be excreted

(Omnicef) • No human data. into breast milk due to its low
• In pregnant rats, oral doses up to 11 times the human dose based molecular weight. However, it was
(U.S. only) on body surface area were not teratogenic, but decreased fetal not detected in breast milk after a
weight occurred at doses > 1.1 times the human dose.1 single 600 mg oral dose.1
• The AAP classifies other
cephalosporins as compatible with
breastfeeding.3
Cefditoren B • See cephalosporins. • No human data.

(Spectracef) • No human data. • Cefditoren excretion in breast milk
• In pregnant rats and rabbits, doses up to about 24 and 4 times, should be expected.1 In most cases,
(U.S. only) respectively, the human dose of 200 mg twice daily based on the effects of this exposure will be
BSA were not teratogenic.1 insignificant.1
• The AAP classifies other
cephalosporins as compatible with
breastfeeding.3
Cefepime B • See cephalosporins. • Cefepime is excreted in human milk in

(Maxipime) • No human data. very low concentrations.1
• No adverse effects on fertility or reproduction, including • The AAP classifies other
embryo toxicity and teratogenicity, were observed in mice, rats, cephalosporin antibiotics as
and rabbits dosed at 1 to 4 times the recommended maximum compatible with breastfeeding.3
human daily dose based on BSA.1
More. . .

Categorya
Cefixime B • See cephalosporins. • No human data.
(Suprax) • In an observational cohort study, cefixime was taken during the • Cefixime excretion in breast milk
1st trimester in 11 pregnancies. The outcomes of these should be expected.1
pregnancies included 2 spontaneous abortions, 1 elective • The AAP classifies other
abortion, 7 normal newborns (1 premature), and 1 unknown cephalosporin antibiotics as
outcome.1 compatible with breastfeeding.3
Cefotaxime B • See cephalosporins. • Cefotaxime is excreted into breast
(Claforan) • No detectable teratogenic risk with cefotaxime and other milk in low concentrations.1
cephalosporin antibiotics was found in a large 2001 population- • The AAP classifies cefotaxime as
based, case-control study of pregnant women.4 compatible with breastfeeding.3
Cefotetan B • See cephalosporins. • Cefotetan is excreted into breast milk
(Cefotan) • Reproduction studies in rats and monkeys found no evidence of in low concentrations.1
impaired fertility or fetal harm at doses up to 20 times the • The AAP classifies other
(U.S. only) human dose.1 cephalosporin antibiotics as
Cefoxitin B • See cephalosporins. • Cefoxitin is excreted into breast milk
(Mefoxin [U.S.]; generics • There were no apparent adverse effects noted in newborns in low concentrations.1
[Canada]) exposed to cefoxitin via the transplacental route.1 • The AAP classifies cefoxitin as
Cefpodoxime B • See cephalosporins. • Cefpodoxime is excreted into breast milk
(Vantin) • No human data.1 in low concentrations.1
• Based on animal reproduction studies, there is no evidence of • The AAP classifies other cephalosporin
(U.S. only) antibiotics as compatible with
impaired fertility or reproductive performance (in rats) or
breastfeeding.3
embryo toxicity or teratogenicity (in rats and rabbits) at doses
• U.S./Canadian product labeling
up to 2 times the human dose based on BSA.1 recommends against use of drug while
breastfeeding.
Cefprozil B • See cephalosporins. • Cefprozil is excreted into breast milk
(Cefzil [U.S.]; generics • No human data.1 in low concentrations.1
[Canada]) • Reproduction studies found no evidence in animals of impaired • The AAP classifies cefprozil as
fertility or, in mice, rats, and rabbits, of fetal harm at doses of compatible with breastfeeding.3
8.5, 18.5, and 0.8 times, respectively, the maximum human
daily dose based on BSA.1
Ceftazidime B • See cephalosporins. • Ceftazidime is excreted into breast
(Fortaz) • Reproduction studies in mice and rats found no evidence of milk in low concentrations.
impaired fertility or fetal harm at doses up to 40 times the • The AAP classifies ceftazidime as
human dose.1 compatible with breastfeeding.3
More. . .

Categorya
Ceftibuten B • See cephalosporins. • No human data, but presence of ceftibuten
(Cedax) • No detectable teratogenic risk with ceftibuten and other in milk should be expected.
(U.S. only) cephalosporin antibiotics was found in a large 2001 population- • The AAP classifies other cephalosporin
based, case-control study of pregnant women.4 antibiotics as compatible with
breastfeeding.3
Ceftriaxone B • See cephalosporins. • Ceftriaxone is excreted into breast
(Rocephin [U.S.]; generics • In a large database review, of the 60 1st trimester exposures to milk in low concentrations.1
[Canada]) ceftriaxone, 4 (6.7%) major birth defects were observed (3 expected), • The AAP classifies ceftriaxone as
including 3 cardiovascular defects (1 expected). A possible compatible with breastfeeding.3
association between ceftriaxone and cardiovascular defects is
suggested, but other factors, such as the mother’s disease, concurrent
drug use, and chance, may be involved. Other cephalosporin antibiotics
from this study have also shown possible associations with congenital
malformations.1
Cefuroxime B • See cephalosporins. • Cefuroxime is excreted into breast milk in
(Ceftin [U.S.]; generics • In a large database review, of the 143 1st trimester exposures to low concentrations.1
[Canada]) cefuroxime, there were 3 (2.1%) major birth defects observed (6 • The AAP classifies other cephalosporin
expected). These data do not support an association between the antibiotics as compatible with
breastfeeding.3
drug and congenital defects.1
• Consider withholding breastfeeding per
U.S./Canadian product labeling.
Cephalexin B • See cephalosporins. • Cephalexin is excreted into breast
(Keflex [U.S.]; generics • In a large database review, of the 3613 1st trimester exposures to milk in low concentrations.
[Canada]) cephalexin, there were 176 (4.9%) major birth defects observed (154 • The AAP classifies other
expected). The data for total defects, cardiovascular defects, and oral cephalosporin antibiotics as
clefts suggest an association between cephalexin and congenital
defects, but other factors, such as the mother’s disease, concurrent drug
use, and chance, may be involved.1
• In another large database review, no teratogenic risk was found to be
associated with cephalexin use during pregnancy.4
Chloramphenicol C • In a large database review, there were 98 1st trimester exposures • The AAP classifies chloramphenicol
and 348 anytime exposures to chloramphenicol. There was no as an agent whose effect on the
evidence to suggest a relationship to large categories of major or nursing infant is unknown, but may be
minor malformations or to individual defects in either group. of concern because of the potential for
• There is one report that cardiovascular collapse (gray syndrome) idiosyncratic bone marrow
developed in babies delivered from a mother treated with suppression.1
chloramphenicol during the final stage of pregnancy.1
• Chloramphenicol should be used with caution at term.1
More. . .

Categorya
Ciprofloxacin C • See fluoroquinolones. • See fluoroquinolones.
(Cipro [U.S.]; generics • In a large database review, of the 132 1st trimester exposures to • Limited human data; however, the
[Canada]) ciprofloxacin, there were 3 (2.3%) major birth defects observed amount of ciprofloxacin in breast milk
(6 expected). These data do not support an association between does not appear to represent a
the drug and congenital defects.1 significant risk to a nursing infant.1
• The AAP classifies ciprofloxacin as
Clarithromycin C • Clarithromycin crosses the human placenta. • No human data.
(Biaxin [U.S.]; generics • A large database review reported exposure to clarithromycin • Because other macrolides are excreted
[Canada]) during the 1st and 2nd trimesters (n=34) for upper respiratory in breast milk, the passage of
infections. Among the 29 known pregnancy outcomes (5 were clarithromycin into milk should be
pending), there were 8 (28%) abortions (4 spontaneous/4 expected.1
voluntary), 20 (69%) normal newborns, and 1 (3%) infant with a • The risk of clarithromycin to the
0.5-cm brown mark on the temple. Although follow-up of the nursing infant is probably minimal,
remaining newborns had not been long enough to completely but caution should be exercised until
exclude the presence of congenital malformations, these the effects of this exposure, if any,
outcomes do not appear to be different from those expected in a have been studied.1
nonexposed population.1
• Toxicity has been observed in animals. Per product labeling,
use only if necessary, especially during 1st three months
gestation.29,30
Clavulanic Acid B • In a large database review, of the 556 1st trimester exposures to • There are no data on potassium
clavulanic acid, there were 24 (4.3%) major birth defects clavulanate and nursing women.
(amoxicillin-clavulanate observed (24 expected).1 • The effects of potassium clavulanate
[Augmentin]) • No adverse effects in the fetus or newborn attributable to the use on the nursing infant are unknown.1
of amoxicillin and potassium clavulanate were observed in
several studies describing the antibiotic use in pregnant women.1
Clindamycin B • There are no reports linking the use of clindamycin with • Clindamycin is excreted into breast
(Cleocin [U.S.]; generics congenital defects.1 milk.1
[Canada]) • In a large database review, of the 647 1st trimester exposures to • The AAP classifies clindamycin as
clindamycin, there were 31 (4.8%) major birth defects observed compatible with breastfeeding.3
(28 expected). These data do not support an association between
the drug and congenital defects.1
• Avoid vaginal clindamycin in second half of pregnancy.19
More. . .

Categorya
Clotrimazole B • See azole antifungals. • It is doubtful that clotrimazole would
(Topical/Vaginal) • Absorption of clotrimazole from the skin and vagina is minimal, posing appear in breast milk since its
(Gyne-Lotrimin, etc. little risk to the unborn baby.1,8 absorption through the skin and
[U.S.]; Canesten, etc. • No adverse effects attributable to clotrimazole have been observed in vagina is minimal.1
[Canada]) studies.1
• In a large database review, of the 2624 1st trimester exposures to
clotrimazole, there were 118 (4.5%) major birth defects observed (112
expected). However, these data do not support an association between
vaginal use of clotrimazole and congenital defects.1
Cloxacillin B • See penicillin derivatives. • No human data.
(Cloxapen [U.S.]; generics • In a large database review, of the 46 trimester exposures to cloxacillin • Because other penicillins are excreted
[Canada]) during the 1st trimester, there were 3 (6.5%) major birth defects in breast milk in low concentrations,
observed (2 expected), including 2 cardiovascular defects (0.5 the presence of cloxacillin in breast
expected) and 1 hypospadias (none expected). Only with the former
milk should be expected.1
defect is there a suggestion of a possible association, but other factors,
including the mother’s disease, concurrent drug use, and chance, may • Also see ampicillin and penicillin G.
be involved.1
Dapsone C • A number of studies have described the use of dapsone during • There is a case of hemolytic anemia in
all stages of human pregnancy. A few fetal or newborn adverse both mother and her infant. The mother
effects directly attributable to dapsone have been reported, but was taking dapsone during the latter two-
no congenital anomalies thought to be due to the drug have been thirds of her pregnancy and during
lactation.1
observed.1
• Although not citing the case of dapsone-
• Neonatal hyperbilirubinemia has been reported (one case) with induced hemolytic anemia in a nursing
maternal dapsone use close to delivery.1 infant described above, the AAP classifies
dapsone as compatible with
breastfeeding.1,3
recommends against use of drug while
breastfeeding.
Daptomycin B • No human data; animal data suggest low risk.1 • No human data.
(Cubicin) • In animal studies, IV doses up to 3 (rats) and 6 (rabbits) times • The high molecular weight should
human dose based on BSA, no evidence of fetal harm was limit excretion into breast milk.
observed.1 However, vancomycin, an antibiotic
• Vancomycin, an antibiotic with a similar spectrum and with a similar spectrum and molecular
molecular weight (about 1486), is known to cross the human weight is excreted into breast milk
placenta late in the 2nd trimester to produce detectable with concentrations nearly identical to
concentrations in amniotic fluid.1 the mother’s trough serum
concentration.1
More. . .

Categorya
Demeclocycline D • See tetracyclines. • See tetracyclines.
Dicloxacillin B • See penicillin derivatives. • No human data.

(Dynapen, etc) • Crosses the placenta into the fetal circulation and amniotic fluid. • Excretion of dicloxacillin into breast
Levels are low compared with other penicillins due to the high milk should be expected, since other
degree of maternal protein binding.1 penicillins are excreted into the breast
(U.S. only) • In a large database review, of the 46 1st trimester exposures to milk in low concentrations. 1
dicloxacillin, there was 1 (2.2%) major birth defect observed (2
expected).1
Doxycycline D • See tetracyclines. • See tetracyclines.
(Periostat, etc. [U.S.];
Doxytab [Canada])
Ertapenem B • No human data. • Limited human data.
(Invanz) • No teratogenicity observed in mice and rats at 3 times the • Ertapenem is excreted into breast milk
recommended human dose.1 based on reports of 5 nursing women
• There is no evidence that any beta-lactam antibiotics cause treated with ertapenem.1
developmental toxicity in humans at therapeutic doses. • The effects on a nursing infant are
Therefore, it is probably safe to use ertapenem anytime during unknown, but are of doubtful clinical
gestation if maternal condition requires its use.1 significance.1
Erythromycin (excluding B • In a large database review, there were 79 1st trimester exposures • Erythromycin is excreted into breast
estolate salt) to erythromycin and 230 exposures for use at any time during milk.1
pregnancy. There was no evidence to suggest a relationship to • The AAP classifies erythromycin as
large categories of major and minor malformations or to compatible with breastfeeding.3
individual defects.1
• In another large database review, of the 6972 1st trimester
exposure to erythromycin, there were 320 (4.6%) major birth
defects observed (297 expected). However, these data do not
support an association between the drug and congenital
malformations.1
Erythromycin estolate N/A • Approximately 10% of 161 women treated with the estolate salt • See erythromycin.
(generics [Canada]) of erythromycin in the 2nd trimester had abnormally elevated
levels of serum glutamic-oxaloacetic transaminase, which
returned to normal after therapy was discontinued.1,9
• It is recommended that pregnant women avoid erythromycin
estolate due to potential for hepatotoxicity.9
More. . .

Categorya
Ethambutol C • Ethambutol, isoniazid, and rifampin combination are considered • Excreted into breast milk.
(Myambutol [U.S.]; Etibi the safest option for treatment of tuberculosis.1,22 • The AAP classifies ethambutol as
[Canada]) • Ophthalmic abnormalities have occurred in infants born to women on compatible with breastfeeding.1
antituberculosis therapy that included ethambutol.27 There are no
reports of long-term follow-up examinations for ocular damage.1
• High doses teratogenic in animals.27,37 No evidence of teratogenicity in
humans.1,37 Avoid in 1st trimester if possible.37
Ethionamide C • Of the 5 human studies describing the outcome of pregnancies • No human data.
(Trecator) exposed to ethionamide, only one of the studies found an • Excretion into breast milk is expected
increased incidence of birth defects (2 cases of Down’s due to low molecular weight.1
(U.S. only) syndrome from 23 exposed infants). The other reports found no
association with congenital malformations.1
• Animal studies suggest teratogenic potential. Do not use in
women who are pregnant or likely to become pregnant unless
use is essential.18,37
Fluconazole C • There are several reports of women treated with 400 mg to • Fluconazole is excreted into breast
(Diflucan [U.S.]; generics 800 mg of fluconazole orally daily throughout the 1st trimester. milk.1
[Canada]) One of the women continued the treatment until delivery. The • No drug-induced toxicity has been
infants were born with grossly dysmorphic features including observed in infants exposed to
NOTE: Recommendations malformations in the head, face, and extremities.1 fluconazole via breastfeeding.1
for use of single-dose oral • In a retrospective review of 289 pregnant women treated with Therefore, fluconazole is probably
fluconazole to treat vaginal either a single dose of fluconazole 150 mg (n=275), multiple safe to use during breastfeeding.1
candida are inconsistent 50 mg doses (n=3), or multiple 150 mg doses (n=11) during or • The AAP classifies fluconazole as
(i.e., second-line agent8,37 shortly before pregnancy for vaginal candidiasis, anomalies compatible with breastfeeding.3
vs. contraindicated38). were only observed in four infants. In each of the four cases • U.S./Canadian product labeling
with congenital anomalies, the mother had taken fluconazole recommends against use of drug while
before conception for 1 to 26 weeks before the last monthly breastfeeding.
menstrual period.1
• The use of fluconazole during the 1st trimester appears to be
teratogenic with continuous daily doses of 400 mg/day or more
according to the limited data.1
• Currently, there is no evidence of increased risk of major
malformations associated with short-term use of 150 mg of
fluconazole.8
• For vaginal candidiasis, only topical azoles are recommended
for use in pregnancy.19,20
• Generally avoid in pregnant women per IDSA.36
More. . .

Categorya
Fluoroquinolones C • Concerns regarding the safety of fluoroquinolones originated • See individual agents.
from reports of arthropathy in animal studies; however, such • U.S./Canadian product labeling
reports are rare in human cases.5,6 recommends against use of drug while
• In a 1993 review on the safety of fluoroquinolones, the authors breastfeeding.
concluded that fluoroquinolones should be avoided during
pregnancy because of the difficulty in extrapolating animal
mutagenicity results to humans and because interpretation of
this toxicity is controversial. The authors were not convinced
that fluoroquinolone-induced fetal cartilage damage and
subsequent arthropathies were a major concern in humans.7
• Data from a prospective follow-up study conducted by the
European Network of Teratology Information Services
(ENTIS), data on 549 pregnancies exposed to fluoroquinolone
(levofloxacin=0; ofloxacin=93) and data on another 116
prospective and 25 retrospective pregnancy exposures to
fluoroquinolones were analyzed. Of the 666 cases with known
outcomes, 32 (4.8%) of the embryos, fetuses, or newborns had
congenital malformations. From previous epidemiology data,
the authors concluded that the 4.8% frequency of malformations
did not exceed the background rate.1
• Because a causal relationship with some of the birth defects
cannot be excluded, fluoroquinolones should be used with
caution, especially during first trimester.1
• Some have suggested that fluoroquinolones should be considered
contraindicated in pregnancy because safer alternatives are usually
available.1 Both CDC and Canadian STD guidelines consider
quinolones to be contraindicated during pregnancy.19,20
Fosfomycin B • Fosfomycin has been used in all trimesters of pregnancy with no • No human data.
(Monurol) apparent harm to the fetus or newborn.1 • Because of its relatively low molecular
weight, excretion into milk should be
expected.1
breastfeeding.
Gemifloxacin C • See fluoroquinolones. • No human data. See fluoroquinolones.
(Factive) • It is unknown if gemifloxacin crosses the human placenta. • The AAP classifies both ciprofloxacin
• Animal data from mice, rats, and rabbits show growth and ofloxacin as compatible with
(U.S. only) retardation of fetus.1 breastfeeding.3
More. . .

Categorya
Gentamicin D • See aminoglycosides. • See aminoglycosides.
• Human data suggest low risk.1 • Small amounts of gentamicin are
• Crosses the placenta into the fetal circulation and amniotic fluid. excreted into breast milk and poorly
1,2
absorbed by the nursing infant. 1 The
levels were low and not likely to cause
clinical effects.2
• The AAP classifies gentamicin as
Griseofulvin C • Limited human data; animal data suggest risk.1 • No human data.
(Fulvicin, etc) • Griseofulvin is tumorigenic, embryotoxic, and teratogenic in • The use of griseofulvin during
some species of animals.1 breastfeeding is not recommended due
• In a large database review, of the 34 1st trimester exposures to to the tumorigenicity and other
griseofulvin, there was 1 (2.9%) major birth defect observed (1 toxicities in animals.1
expected). The number of exposure is too small to draw any
conclusions.1
•
Per product labeling, contraindicated during pregnancy.31
Imipenem/Cilastatin C • Limited human data; animal data suggest low risk.1 • Limited human data.
(Primaxin) • Crosses the placenta to the fetus.1 • Small amount, comparable to those for
• Animal studies in pregnant rabbits and rats showed no evidence other beta-lactam antibiotics, is
of adverse fetal effect at doses up to 2 to 30 times the maximum excreted into breast milk.1
human dose.1 • The effects, if any, on a nursing infant
are unknown.1
Isoniazid C • In a large database review; of the 11 1st trimester exposures, one (0.1) • Both isoniazid and its metabolite
major birth defect was observed (0.5 expected).1 acetylisoniazid are excreted in breast
• Association between isoniazid and hemorrhagic disease of the newborn milk.1
has been suspected in two infants. However, the mothers were also • The AAP classifies isoniazid as
treated with rifampin and ethambutol. Although other reports of this
potentially serious reaction have not been found, prophylactic vitamin
K is recommended at birth.1 • Monitor for rare instances of jaundice
• The CDC recommends a combination of isoniazid (plus in the nursing infant.41
pyridoxine), rifampin, and ethambutol as treatment of choice for
pulmonary tuberculosis during pregnancy and breastfeeding.22
• The American Thoracic Society recommends use of the drug for
tuberculosis occurring during pregnancy.1
• INH-induced hepatotoxicity more frequent during
pregnancy/postpartum. Monthly LFTs recommended.37
More. . .

Categorya
Itraconazole C • In an observational cohort study, itraconazole was taken orally • Limited human data; potential
(Sporanox) during the 1st trimester in 41 pregnancies. The outcomes of toxicity.1
these pregnancies included 1 ectopic pregnancy, 2 spontaneous • Itraconazole is excreted into breast
abortions, 6 elective abortions, 2 cases lost to follow-up, and 30 milk.1
normal newborns (1 premature). One of the normal full-term • The potential effects of itraconazole
newborns had a minor congenital anomaly (thin, prominent, and exposure to nursing infants have not
protruding left ear).1 been studied, therefore, women taking
• Another azole antifungal, fluconazole, has demonstrated itraconazole should probably not
possible dose-related association with major malformations. breastfeed.1
Therefore, is best to avoid itraconazole during organogenesis
(1st trimester).1
• Per IDSA, itraconazole should generally be avoided in pregnant
women.36
Kanamycin D • See aminoglycosides. • See aminoglycosides.

(U.S. only) • Eighth cranial nerve damage has been reported following in • Limited human data; probably
utero exposure to kanamycin. 1 compatible. 1
• In a retrospective survey of 391 mothers who had received • Kanamycin is excreted into breast
kanamycin, 50 mg/kg, for prolonged periods during pregnancy, milk.
9 (2.3%) children were found to have hearing loss. 1 • Ototoxicity not expected in infant
• Except for ototoxicity, no reports of congenital defects due to since oral absorption of kanamycin is
kanamycin have been located. 1 low. 1
• Avoid use in pregnancy if possible.37 • The AAP classifies kanamycin as
Ketoconazole (Oral) C • Ketoconazole is embryotoxic and teratogenic in rats at a dose 10 • Ketoconazole is excreted into breast
(Nizoral, etc) times the maximum recommended human dose based on milk.
weight.1 • The effects on the nursing infant from
• In a large database review, of the 20 1st trimester exposures to exposure to ketoconazole in the milk
oral ketoconazole, no major birth defects were observed (one are unknown.
expected). Since the study, the FDA has received 6 reports of • Other agent may be preferred due to
limb defects.1 potential for liver toxicity.41
• Generally avoid in pregnant women.36 • The AAP classifies ketoconazole as
breastfeeding.
More. . .

Categorya
Levofloxacin C • See fluoroquinolones. • See fluoroquinolones.
(Levaquin) • Human data suggest low risk.1 • Limited human data.
• Levofloxacin should be use with caution during pregnancy, • The use of levofloxacin during
especially during the 1st trimester.1 lactation was not recommended when
the product was first marketed due to
the potential of arthropathy and other
toxicity in the nursing infant.1
U.S./Canadian product labeling still
recommend against use while
breastfeeding.
• Photosensitivity has also been
reported in nursing infants who have
been exposed to levofloxacin via
breastfeeding.1
• The AAP classifies both ciprofloxacin
and ofloxacin as compatible with
breastfeeding.3
Linezolid C • No human data. • No human data.

(Zyvox [U.S.]; Zyvoxam • No evidence of teratogenicity was observed in mice and rats at • The molecular weight is low enough
[Canada]) doses 4 and 1 times the expected human exposure based on that excretion into breast milk should
AUC, respectively. However fetal toxicity (embryo death, total be expected.1
litter loss, decreased fetal weight, and an increased incidence of • Because myelosuppression has
costal cartilage fusion) were observed at this dose. occurred in dogs and rats and
• It is unknown if linezolid crosses the human placenta. However, reversible thrombocytopenia in adult
the molecular weight is low enough that transfer to the fetus humans, women taking linezolid
should be expected.1 should probably not breastfeed. 1
• If no other alternatives are available and linezolid must be used,
the maternal benefit appears to outweigh the unknown fetal
risk.1
Meropenem B • No human data; animal data suggest low risk.1 • No human data.
(Merrem) • Animal studies in rats and cynomolgus monkeys at doses up to • The potential effects, if any, on
1.8 and 3.7 times, respectively, the usual human dose found no nursing infants are unknown.1
evidence of impaired fertility or fetal harm.1
• The fetal risk of use before 28 weeks of gestation is unknown.1
More. . .

Categorya
Metronidazole B • In a large database review, 31 who had 1st trimester exposure to • Metronidazole is excreted into breast
(Oral, IV) metronidazole. A possible association with malformations was milk.1
(Flagyl, etc) found based on defects in 4 children (RR=2.02), but • Unnecessary exposure to
independent confirmation is required.1 metronidazole should be avoided since
• In another large database review, of the 2445 1st trimester the drug is mutagenic and
exposures to metronidazole, there were 100 (4.1%) major birth carcinogenic in some test species.1
defects observed (97 expected). Only with oral clefts is there a • If a single 2 gram oral dose of
suggestion of possible association.1 metronidazole is used for
• Oral metronidazole is contraindicated during the 1st trimester in trichomoniasis, the AAP recommends
patients with trichomoniasis per U.S. product labeling.1,23 discontinuing breastfeeding for 12-24
(Note: Canadian product labeling and some U.S. products hours to allow excretion of the drug.1,3
consider drug contraindicated during 1st trimester regardless of
indication.)24,25 Metronidazole use during 2nd and 3rd trimester
for trichomoniasis or bacterial vaginosis is acceptable.1
• For other indications, metronidazole can be used during
pregnancy if there are no other alternatives.1
• Some recommend routine screening for and treatment of
asymptomatic bacterial vaginosis only if patient high-risk for
preterm birth.13,14,19
• Considered safe for use during pregnancy per CDC/Canadian
STD guidelines.19,20
Metronidazole B • No human data; see metronidazole oral/IV. • See oral and IV metronidazole.
(Topical, Vaginal) • Because metronidazole is a carcinogen in rodents, it should be
(Metrogel, etc) used during pregnancy only if clearly needed. 15-17
Micafungin C • No human data; animal data suggest moderate risk.1 • No human data.
(Mycamine) • Per IDSA, use with caution during pregnancy.36 Use not • The high molecular weight, low lipid
recommended per CDC.37 solubility, and very high protein
binding suggests that excretion into
breast milk will be limited. However,
the drug is excreted into the milk of
lactating rats.1
More. . .

Categorya
Miconazole C • See azole antifungals. • No data available.
(Monistat, etc) • Miconazole is normally used as a topical antifungal and small • Remove excess cream or ointment
amounts are absorbed from the vagina.1 from the nipples before nursing.41
• Use of miconazole vaginally has not been associated with
increased congenital malformations.1
• In a large database review, of the 2092 1st trimester exposures
to miconazole, the estimated relative risk for birth defects from
the data was 1.02 (95% CI 0.9-1.2). No association was found
between miconazole use and oral clefts, spina bifida, or
cardiovascular defects. However, the possibility of an
association with other specific defects cannot be excluded.1
• If possible, avoid vaginal use in 1st trimester.32
Minocycline D • See tetracyclines. • See tetracyclines.

(Solodyn, etc [U.S.];
generics [Canada])
Moxifloxacin C • See fluoroquinolones. • See fluoroquinolones.

(Avelox) • Animal data showed growth retardation and delayed fetal • No human data.
skeletal development in rats exposed to moxifloxacin.1 • The AAP classifies both ciprofloxacin
breastfeeding.3
recommend against use of
moxifloxacin while breastfeeding.
Nafcillin B • See penicillin derivatives and Penicillin G. • No data available.
(Unipen, etc) • No reports linking nafcillin use with congenital defects have • See Penicillin G.
been located.1
(U.S. only)
More. . .

Categorya
Nitrofurantoin B • Data suggest risk in 3rd trimester.1 • Limited human data.
(Macrobid, Macrodantin • Case-control studies and case series involving thousands of • Nitrofurantoin is excreted into breast
[U.S.]; generics [Canada]) women who received nitrofurantoin in pregnancy reported no milk.1
increase of major malformations among the newborns. In • Based on measurement of
addition, a meta-analysis failed to show teratogenic risk with nitrofurantoin excretion in milk,
first-trimester use of nitrofurantoin.5 investigators estimated that if a
• In a large database review, of the 1292 1st trimester exposures to 60 kg woman was taking
nitrofurantoin, there were 52 (4.0%) major birth defects nitrofurantoin 100 mg twice daily, the
observed (55 expected). However, these data do not support an infant dose would be 0.2 mg/kg, or
association between the drug and congenital defects.1 about 6% of the mother's weight-
• A retrospective analysis of 91 pregnancies in which adjusted dose.1
nitrofurantoin was used yielded no evidence of fetal toxicity. • Although this exposure was thought to
Other studies have also supported the safety of this drug in be low, nursing infants younger than 1
pregnancy.1 month of age and those with a high
• A retrospective, case-control study (n=13,155) suggests an frequency of G-6-PD deficiency or
association with birth defects. However, the study has multiple sensitivity to nitrofurantoin may be at
limitations and does not establish a causal relationship.40 risk for toxicity.1
• Nitrofurantoin can theoretically induce hemolytic anemia in • The AAP classifies nitrofurantoin as
glucose-6-phosphate dehydrogenase (G-6-PD)–deficient compatible with breastfeeding.3
patients and in patients whose red blood cells are deficient in • U.S. product labeling recommends
reduced glutathione; however, cases of this toxicity are rare.1,5 against use of drug while
• Contraindicated in pregnant women at term (38 to 42 weeks breastfeeding (Canadian labeling
gestation), during labor and delivery, or when onset of labor is advises caution).
imminent.1,21
Norfloxacin C • See fluoroquinolones. • See fluoroquinolones.
(Noroxin [U.S.]; generics • The use of norfloxacin during human gestation does not appear • No human data.
[Canada]) to be associated with an increased risk of major congenital • Although it is not known whether
malformations. However, a causal relationship with some of the norfloxacin is excreted into human
birth defects cannot be excluded.1 milk, the high concentrations of the
• Norfloxacin should be used with caution during pregnancy, drug found in the milk of ewes, the
especially during the 1st trimester.1 relatively low molecular weight (about
319), and the excretion of other
quinolones suggest that the drug will
probably be in milk.1
• The AAP classifies both ciprofloxacin
breastfeeding.3
More. . .

Categorya
Nystatin C • Nystatin is poorly absorbed after oral administration and from • Nystatin is poorly absorbed, if at all.1
intact skin and mucous membranes.1 • Excretion into breast milk is not
• In a large database review of the 489 1st trimester exposures, a expected.1
total of 20 (4.1%) major birth defects were observed (21
expected).1
• Topical nystatin is probably a safe alternative to topical azole
antifungals for the treatment of vaginal yeast infections.9
• No association with the risk of major malformations have been
observed in numerous trials.8
Ofloxacin C • See fluoroquinolones. • See fluoroquinolones.

(Floxin [U.S.]; generics • Although a number of birth defects have occurred in the • Limited human data.
[Canada]) offspring of women who had taken ofloxacin during pregnancy, • Excreted into breast milk.1
the use of ofloxacin during human gestation does not appear to • The use of ofloxacin during lactation
be associated with an increased risk of major congenital was not recommended when the
malformations.1 product was first marketed due to the
• A causal relationship with some of the birth defects cannot be potential of arthropathy and other
excluded. Because of this and the available animal data, toxicity in the nursing infant.1
ofloxacin should be used with caution during pregnancy, • Photosensitivity has also been
especially during the 1st trimester.1 reported in nursing infants who have
been exposed to ofloxacin via
breastfeeding.1
• The AAP classifies ofloxacin as
Oxacillin B • See penicillin derivatives. • Oxacillin is excreted in breast milk in
(Bactocill, etc) • Crosses the placenta in low concentrations.1 low concentrations.1
(U.S. only)
Oxytetracycline D • See tetracyclines. • See tetracyclines.
Paromomycin C • See aminoglycosides. • No human data.1
(Humatin) • Limited human data.1 • Paromomycin excretion in human
• No reports linking this agent with congenital malformations milk is not expected because the drug
have been located.1 is not absorbed into the systemic
• Two women, one at 13 weeks' and the other at 23 weeks' circulation after oral dosing.1
gestation, were treated for a symptomatic intestinal infection
caused by Giardia lamblia. Both delivered normal female
infants at term.1
More. . .

Categorya
Penicillin G B • See penicillin derivatives. • Excreted into breast milk in low
• In a controlled study, 110 patients received one to three concentrations.1
antibiotics during the 1st trimester for a total of 589 weeks.
Penicillin G was given for a total of 107 weeks. The incidence
of birth defects was no different than in a nontreated control
group.1
Penicillin V B • See penicillin derivatives. • Excreted into breast milk in low
• In a large database review, of the 4597 1st trimester exposures to concentrations.2
penicillin V, there were 202 (4.4%) major birth defects observed
(195 expected). However, these data do not support an
association between the drug and congenital defects.1
Penicillin Derivatives B • Penicillins transferred to the fetus and amniotic fluid reach • Excreted into breast milk in low
therapeutic levels.2 concentrations.1,2
• In a large database review, of the 3546 cases of 1st trimester • See individual agents for details.
exposure to penicillin derivatives and 7171 cases of exposures
for use anytime during pregnancy, there was no evidence found
to suggest a relationship to large categories of major or minor
malformations or to individual defects.1
Piperacillin/Tazobactam B • Rapidly crosses the placenta to the fetus.1 • Excreted into breast milk in low
(Zosyn [U.S.], Tazocin • No reports linking the use of piperacillin with congenital defects concentrations.1
[Canada]) in humans have been located.1
• No adverse maternal or fetal effects have been observed when
used between 24 and 35 weeks’ gestation in women with
premature rupture of the membranes to delay delivery.1
Posaconazole C • No human data; animal data suggest risk.1 • No human data.
(Noxafil [U.S.]; Posanol • See fluconazole and itraconazole for related risks. • Excretion to breast milk should be
[Canada]) • Avoid posaconazole during pregnancy, especially in the 1st limited due to its molecular weight,
trimester.1 low metabolism, long elimination
• If use can’t be avoided, use lowest dose possible.1 half-life, and high plasma protein
• Per IDSA, generally avoid in pregnant women.36 binding.1
• The effects on the nursing infant is
unknown, but it’s been associated with
hepatic toxicity, nausea, and vomiting
in adults.1
breastfeeding.
More. . .

Categorya
Quinupristin/Dalfopristin B • No human data. • No human data; potential toxicity.10
(Synercid) • Quinupristin/dalfopristin crosses rat placenta and is expected to • The relatively high molecular weights for
cross human placenta.1 the two components suggest that only
(U.S. only) small amounts, if any, will pass into
• There is no evidence of impaired fertility or fetal harm in
human milk.1
pregnant mice, rats, and rabbits at approximately 0.5, 2.5, and
• Quinupristin/dalfopristin is not
0.5 times the human dose, respectively.1 recommended during breastfeeding due to
• Because the indication for the combination involves potentially the potential of the development of
life-threatening infections, the maternal benefit of therapy resistance to quinupristin/dalfopristin.1
appears to far outweigh the unknown embryo or fetal risk.1
Rifabutin B • No human data; animal data suggest low risk.1 • No human data.
(Mycobutin) • Animal studies showed that doses < 40 times recommended • The molecular weight, moderate plasma
human daily dose were not teratogenic in rats and rabbits, but protein binding, and prolonged terminal
the high dose caused a decrease in fetal viability.1 half-life suggest excretion into milk should
be expected.1
• It is unknown if rifabutin or its active metabolites crosses the • Milk may be stained a brown-orange
human placenta. However, the low molecular weight, moderate color.1
plasma protein binding, high lipid solubility, and prolonged • Potential serious toxicity to the nursing
terminal half-life suggests that passage to the fetus will occur.1 infant includes leucopenia, neutropenia,
• Therapy should not be withheld if maternal benefit outweighs rash, etc.1 (U.S./Canadian product
the unknown fetal risk.1 labeling recommends against use while
breastfeeding.)
Rifampin C • Teratogenicity in rodents has been reported with oral doses 15- • Rifampin is excreted into human milk
(Rifadin [U.S.]; Rofact 25 times the human dose.1 in a low concentration, which presents
[Canada]) • Studies with rabbits showed no evidence of teratogenicity.1 a very low risk to the nursing infant.1
• In a large database review, of the 20 1st trimester exposures to • No reports describing adverse effects
rifampin, there were no major birth defects observed (one in nursing infants have been located.1
expected).1 • The AAP classifies rifampin as
• Rifampin can potentially cause hemorrhagic disease in the compatible with breastfeeding.3
newborn and mother when given in the last few weeks of • U.S./Canadian product labeling
pregnancy. Prophylactic vitamin K is recommended to prevent recommends against use of drug while
this serious complication.1 breastfeeding.
• The CDC recommends a combination of isoniazid (plus
pyridoxine), rifampin, and ethambutol as treatment of choice for
pulmonary tuberculosis during pregnancy and breastfeeding.22
• One report described 9 malformations in 204 pregnancies that
went to term (incidence=4.4%, which is similar to the expected
frequency of defects in a healthy nonexposed population, but
much higher than other tuberculosis patients [1.8%]).1
More. . .

Categorya
Rifapentine C • Limited human data; animal data suggest risk. • No human data.
(Priftin) • When taken in the last few weeks of pregnancy, rifapentine may • It is unknown if rifapentine is excreted
cause hemorrhage in both the mother and newborn (similar to into breast milk. However, the molecular
(U.S. only) that observed with rifampin).1 Prophylactic vitamin K weight is low enough that passage into
breast milk should be expected.1
recommended to prevent serious complication.1
• Breast milk may be discolored.1
• Avoid rifapentine during 1st trimester until more human data are • The effects of this exposure, if any, on a
available.1 nursing infant are unknown.1
• The AAP classifies rifampin, a closely
related antibiotic, as compatible with
breastfeeding.3
• Product labeling recommends against use while
breastfeeding.
Rifaximin C • No human data; animal data suggest risk. • No human data.
(Xifaxan) • Teratogenic in rats and rabbits. The adverse effects included • The molecular weight (about 786) is
cleft palate, agnathia, jaw shortening, hemorrhage, partially low enough for excretion into breast
(U.S. only) open eye, small eyes, brachygnathia, incomplete ossification, milk, but only very small amounts of
and increased thoracolumbar vertebrae.1 the antibiotic are absorbed into the
• It is not known if rifaximin crosses the human placenta, but its systemic circulation.1
molecular weight is low enough for passive transfer.1 • The effects of this exposure on a
• Although the embryo/fetal risk is suspected to be low due to nursing infant are unknown but appear
minimal absorption, rifaximin should be avoided during 1st to be negligible.1
trimester until human data are available.1 • Product labeling recommends against
use of drug while breastfeeding.
Streptomycin D • See aminoglycosides. • See aminoglycosides.
• Several cases of maternal use of streptomycin during pregnancy • Streptomycin is excreted into the
resulted in infant ototoxicity have been reported. However, in breast milk.1
general, the risk of congenital ototoxicity, cochlear or vestibular, • Ototoxicity would not be expected in
from streptomycin is low, especially with careful dosage nursing infant of mother who received
calculations and the duration of fetal exposure is limited.1 streptomycin since oral absorption of
• Except for eighth cranial nerve damage, no reports of congenital streptomycin is poor.1
defects caused by streptomycin have been located.1 • The AAP classifies streptomycin as
• In a large database review, there were 135 1st trimester compatible with breastfeeding.3
exposures to streptomycin and 355 exposures recorded for use
any time during pregnancy. There was no evidence to suggest a
relationship to large categories of major or minor malformations
or to individual defects in either group.1
• Avoid use during pregnancy if possible.37, 39
More. . .

Categorya
Sulbactam B • Sulbactam is always given in combination with ampicillin. It • Sulbactam is excreted into the breast
(ampicillin/sulbactam has caused no harm in animal reproduction studies, but reports milk of animals (sheep and goats) and
[Unasyn]) of human exposure in early gestation are lacking.1 However, humans.1
none of the penicillins has been shown to be teratogenic. • The potential effects of exposure to
(U.S. only) Sulbactam readily crosses the human placenta to the fetus. sulbactam on the nursing infant are
Although no direct adverse effects of this exposure on the fetus unknown but are probably similar to
or newborn have been reported, use of ampicillin/sulbactam those that might occur with other
combination near delivery may result in superinfection with antibiotics such as modification of
resistant bacteria in the newborn.1 bowel flora, direct effects on the
infant (e.g., allergy or sensitization).1
• The AAP classifies sulbactam as
Sulfamethoxazole/ C • Sulfonamides as a group do not appear to pose a serious • The AAP classifies TMP-SMX as
Trimethoprim teratogenic risk. However, trimethoprim is a folic acid compatible with breastfeeding.3
(Bactrim DS, etc [U.S.]; antagonist and its use in 1st trimester has been associated with • U.S./Canadian product labeling
generics [Canada]) structural defects (e.g., neural tube and cardiovascular defects).1 considers drug contraindicated in
• A retrospective study suggests sulfonamides are associated with lactation.
birth defects. However, the study has multiple limitations and
does not establish a causal relationship.40
• Sulfamethoxazole can persist in neonatal circulation for several
days after delivery if taken near term and there is a theoretical
risk of sulfonamides increasing unbound bilirubin owing to
competitive protein binding.1,5,7
• In most cases, TMP-SMX should be avoided during the 1st
trimester and after 32 weeks of gestation.1,5,7,9
• Per product labeling, TMP-SMX contraindicated during
pregnancy.
Telithromycin C • No human data; animal data suggest low risk.1 • No human data.
(Ketek) • Telithromycin may cause severe hepatocellular hepatitis that can • Excretion into breast milk is
be fatal.1 expected.1
• Avoid use of telithromycin in human pregnancy until more • Erythormycin, a closely related
human data are available.1 antibiotic, is considered compatible
with breastfeeding.1
• Observe nursing infant for the most
common adverse effects reported in
adults, such as diarrhea, nausea,
vomiting, headache, and dizziness.1
More. . .

Categorya
Terbinafine B • No human data. • Terbinafine is excreted into human milk.3
(Lamisil [U.S.]; generics • No evidence of fetal harm has been found in animal studies at • The effects on a nursing infant are
[Canada]) doses up to 12 times the maximum recommended human dose unknown.3
based on BSA in rats 9 times the maximum recommended • U.S./Canada product labeling recommends
against use while breastfeeding.
human dose in rabbits.1
• Topical terbinafine should not be applied
• Product labeling recommends against use during pregnancy
to breasts.
(oral or topical).33,34
Terconazole C • No human data. • No data available.
(Terazol, etc) • See azole antifungals. • Product labeling recommends against
• Terconazole is available as either a vaginal cream or use of drug while breastfeeding.
suppositories and is absorbed into the systemic circulation in
humans after vaginal administration.3
terconazole a total of 34 (2.9%) major birth defects were
observed (48 expected). However, these data do not support an
association between terconazole and congenital defects.1
Tetracycline D • See tetracyclines. • See tetracyclines.
Tetracyclines D • Contraindicated in 2nd and 3rd trimesters.1 However, evidence of • See individual agents.
embryotoxicity noted in animals treated early in pregnancy.26 • Tetracycline is excreted into breast
• Tetracyclines, as a class, should not be used during pregnancy milk in low concentrations.1
unless absolutely necessary.26 • Theoretically, dental staining and
• Problems attributable to the use of the tetracyclines during or inhibition of bone growth could occur
around the gestational period include: adverse effects on fetal in breastfed infants whose mothers
teeth and bones, maternal liver toxicity, congenital defects, were taking tetracycline. However, the
miscellaneous effects.1 possibility seems remote, because
• In a large database review, there were 341 1st trimester tetracycline serum levels in infants
exposures to tetracycline, 14 to chlortetracycline, 90 to exposed in such a manner were
demeclocycline, and 119 to oxytetracycline. For use anytime in undetectable (<0.05 mcg/mL).1
pregnancy, 1336 exposures were recorded for tetracycline, 0 for • The AAP classifies tetracycline as
chlortetracycline, 280 for demeclocycline, and 328 for compatible with breastfeeding.3
oxytetracycline. No evidence was found to suggest a • U.S./Canadian product labeling
relationship to large categories of major or minor malformations recommends against use while
or to individual defects with chlortetracycline, demeclocycline, breastfeeding.
or oxytetracycline. However, the sample size is extremely small,
and safety should not be inferred from these negative results.1
There was evidence to suggest a relationship to minor, but not
major malformations with tetracycline.1
More. . .

Categorya
Tigecycline D • Tigecycline is a glycylcycline broad-spectrum antibacterial • No human data.
(Tygacil) agent, which is structurally related to the tetracycline class of • Tigecycline is expected to be excreted
antibiotics and may have similar adverse effects.1 into the breast milk based on its
• Similar to tetracyclines, tigecycline can permanently discolor molecular weight (about 586),
the teeth if used in the second half of pregnancy.1 prolonged elimination half-life, and
• Use in the 1st trimester probably does not represent a major risk wide distribution in tissues.1
to the embryo or fetus, but use in later trimesters should be • It is best to not to nurse if a woman is
avoided.1 receiving this antibiotic.1
Tinidazole C • Limited human data. • The AAP classifies tinidazole as an

(Tindamax) • Tinidazole is chemically related to metronidazole, and there is agent whose effect on nursing infants
no convincing evidence of embryo or fetal harm with is unknown but may be of concern.1
(U.S. only) metronidazole.11 • Discontinue breastfeeding while being
• Tinidazole can be used in cases where metronidazole has failed treated and for 3 days following the
to eradicate the infection.1,11 last dose.35
• Contraindicated during 1st trimester per product labeling.35
Tobramycin D • Human data suggest low risk.1 • See aminoglycosides.

• See aminoglycosides.
tobramycin, there were 3 (3.7%) major birth defects observed (3
expected), one of which was a cardiovascular defect (1
expected).1
Vancomycin C • There are no cases of congenital defects attributable to • Limited human data.
(Vancocin [U.S.]; generics vancomycin and the manufacturer has received reports on the • Vancomycin is excreted into breast
[Canada]) use of vancomycin in pregnancy without adverse fetal effects.1 milk.1
• Vancomycin crosses the human placenta and appears in • Vancomycin is poorly absorbed from
umbilical cord blood after IV maternal treatment. Amniotic the normal intact gastrointestinal tract,
fluid and umbilical cord blood concentrations during the early and thus, systemic absorption would
3rd trimester are comparable to maternal blood levels (fetal- not be expected.1
maternal serum concentration ratio of 0.76).2 • Product labeling recommends against
use of drug while breastfeeding.
More. . .

Categorya
Voriconazole D • No human data. Teratogenic in animals.1 • No human data; potential toxicity.1
(Vfend) • A closely related antifungal, fluconazole, is a suspected • Excretion to breast milk is expected
teratogen. Therefore, voriconazole should be avoided during 1st with its low molecular weight.1
trimester.1 • There is potential for toxicity in
• Per IDSA, voriconazole contraindicated during pregnancy nursing infants. Therefore, women
because of fetal abnormalities observed in animals.36 taking voriconazole should not
breastfeed.1
a. FDA Categories for the use of medications in pregnancy:12

• A: adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.
• B: Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women.
OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to
the fetus.
• C: Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. OR
No animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.
• D: Studies, adequate, well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy
may outweigh the potential risk.
• X: Studies, adequate, well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities.
The use of the product is contraindicated in women who are or may become pregnant.
On-line resources:
• Motherisk. http://www.motherisk.org/index.jsp. Offers consumers answers to questions about morning sickness and the risk or safety of
medications, disease, chemical exposure, and more. Provides teratogen information for healthcare professionals and updates on
Motherisk’s continuing reproductive research.
• Perinatology.com. http://www.perinatology.com/. Provides teratogen information for healthcare professionals and links to clinical
guidelines and more.
• Organization of Teratology Information Specialists (OTIS). http://www.otispregnancy.org/. Provides medical consultation on prenatal
exposures for consumers and healthcare professionals.
• OBfocus. http://www.obfocus.com/. Provides information for healthcare professionals and consumers on pregnancy related issues,
including drug exposure. Provides a list of resources on high risk pregnancy.
• Drug and Lactation Database (LactMed). http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT. Provides information on drug use during
lactation. Each drug has a drug monograph that discusses its safety in lactation.
More. . .
Users of this document are cautioned to use their own http://www.fda.gov/fdac/features/2001/301_preg.html

professional judgment and consult any other necessary (Accessed April 12, 2009).
or appropriate sources prior to making clinical 13. Okun N, Gronau KA, Hannah ME. Antibiotics for
judgments based on the content of this document. Our bacterial vaginosis or Trichomonas vaginalis in
pregnancy: a systematic review. Obstet Gynecol
editors have researched the information with input from
2005;105:857– 68.
experts, government agencies, and national 14. Yudin MH, Money DM. Screening and management
organizations. Information and Internet links in this of bacterial vaginosis in pregnancy. J Obstet
article were current as of the date of publication. Gynaecol Can 2008;30:702-16.
15. Product information for Metrogel. Galderma
Project Leader in preparation of this Detail- Laboratories, L.P. Fort Worth, Texas 76177. July
Document: Wan-Chih Tom, Pharm.D. 2004.
16. Product information for Metrogel-Vaginal. 3M
Pharmaceuticals. Northridge, CA 91324. December
References 2006.
1. Briggs GG, Freeman RK, Yaffe SJ. Drugs in 17. Product monograph for Metrogel. Galderma Canada
th
pregnancy and lactation. 8 ed. Philadelphia, PA: Inc. Thornhill, Ontario L3T 7W3. July 17, 2007.
Lippincott Williams & Wilkins, 2008. 18. Product information for Trecator. Wyeth
http://www.briggsdrugsinpregnancy.com. Pharmaceuticals, Inc. Philadelphia, PA 19101.
2. Nahum GG, Uhl K, Kennedy DL. Antibiotic use in November 2007.
pregnancy and lactation. Obstet Gynecol 19. CDC, Workowski KA, Berman SM. Sexually
2006;107:1120-38. transmitted disease treatment guidelines, 2006.
3. Committee on Drugs. American Academy of MMWR Recomm Rep 2006;55(RR-11):1-94.
Pediatrics. Transfer of drugs and other chemicals 20. Public Health Agency of Canada. Canadian
into human milk. Pediatrics 2001;108:776-89. guidelines on sexually transmitted infections.
4. Czeizel AE, Rockenbauer, M, Sorensen HT, Olsen J. Pregnancy. Updated 2008. http://www.phac-
Use of cephalosporins during pregnancy and in the aspc.gc.ca/std-mts/sti_2006/pdf/604_Pregnancy.pdf.
presence of congenital abnormalities: a population- (Accessed May 19, 2009).
based, case-control study. Am J Obstet Gynecol 21. Product information for Macrobid. Proctor & Gamble.
2001;184;1289-96. Cincinnati, OH 45202. January 2009.
5. Lee M, Bozzo P, Einarson A, Koren G. Urinary tract 22. CDC. Tuberculosis and pregnancy. October 2008.
infections in pregnancy. June 2008. Motherisk.org. http://www.cdc.gov/tb/pubs/tbfactsheets/pregnancy.p
http://www.motherisk.org/prof/updatesDetail.jsp?cont df. (Accessed May 17, 2009).
ent_id=882. (Accessed April 11, 2009). 23. Product information for Flagyl. G.D. Searle LLC
6. Pregnancy Team, Food and Drug Administration. (Division of Pfizer). New York, NY 10017. August
Cipro (ciprofloxacin) use by pregnant and lactating 2006.
women. Center for Drug Evaluation and Research. 24. Product monograph for Flagyl. Sanofi-Aventis
Food and Drug Administration. October 30, 2001. Canada. Laval, Quebec H7L 4A8. September 27,
http://www.fda.gov/cder/drug/infopage/cipro/cipropre 2007.
g.htm. (Accessed April 13, 2009). 25. Product information for Flagyl ER. G.D. Searle LLC
7. Sivojelezova A, Einarson A, Shuhaiber S, Koren G. (Division of Pfizer). New York, NY 10017. August
Trimethoprim-sulfonamide combination therapy in 2006.
early pregnancy. Can Fam Physician 2003;49:1085- 26. Product information for tetracycline. Barr Labs.
6. Pomona, NY. 10970. February 2006.
8. Soong D, Einarson A. Vaginal yeast infections http://dailymed.nlm.nih.gov. (Accessed May 19,
during pregnancy. Can Fam Physician 2009;55:255- 2009).
6. 27. Product information for ethambutol. Versa Pharm
9. Einarson A, Shuhaiber S, Koren G. Effects of Inc. Marietta, GA 30062-2260. April 2005.
antibacterials on the unborn child. What is known 28. Product information for Capastat. Eli Lilly.
and how should this influence prescribing. Paediatr Indianapolis, IN 46285. January 2008.
Drugs 2001;3:803-16. 29. Product information for Biaxin. Abbot Labs. North
10. Czeizel AE, Rockenbauer M, Olsen J. Use of Chicago, IL 60064. October 2008.
antibiotics during pregnancy. Eur J Obstet Gynecol 30. Product monograph for Biaxin. Abbott Labs. Saint-
Reprod Biol 1998;81:1-8. Laurent, Quebec H4S 1Z1. April 15, 2009.
11. Donders GG. Treatment of sexually transmitted 31. Product information for Gris-Peg. Pedinol Pharm.
bacterial diseases in pregnant women. Drugs Farmingdale, NY 11735. January 2007.
2000;59:477-85. 32. Product information for miconazole suppositories.
12. Meadows M. Pregnancy and the drug dilemma. FDA Alpharma USPD. Baltimore, MD 21244. December
Consumer Magazine. May-June 2001. 2005.
More. . .
33. Product information for Lamisil. Novartis. East mts/sti_2006/pdf/408_Vaginal_Discharge.pdf.

Hanover, NJ 07936. November 2005. (Accessed June 3, 2009).
34. Product monograph for Lamisil. Novartis Canada. 39. American Thoracic Society, CDC, and Infectious
Dorval, Quebec H95 1A9. January 30, 2008. Disease Society of America. Treatment of
35. Product monograph for Tindamax. Mission Pharm. tuberculosis. MMWR 2003;52(RR-11):1-77.
San Antonio, TX 78230-1355. May 2007. 40. Crider KS, Cleves MA, Reefhuis J, et al.
36. Pappas PG, Kauffman CA, Andes D, et al. Clinical Antibacterial medication use during pregnancy and
practice guidelines for the management of risk of birth defects. National Birth Defects
candidiasis: 2009 update by the Infectious Diseases Prevention Study. Arch Pediatr Adolesc Med
Society of America. Clin Infect Dis 2009;48:503-35. 2009;163:978-85.
37. CDC. Guidelines for prevention and treatment of 41. U.S. National Library of Medicine. Toxicology Data
opportunistic infections in HIV-infected adults and Network (Toxnet). Drug and Lactation Database
adolescents. MMWR 2009;58(No. RR-4):1-207. (LactMed). February 12, 2010.
38. Public Health Agency of Canada. Canadian http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT.
guidelines on sexually transmitted infections, vaginal (Accessed March 28/29, 2010 and April 6, 2010).
discharge (bacterial vaginosis, vulvovaginal
candidiasis, trichomoniasis. Updated January 2008.
http://www.phac-aspc.gc.ca/std-
Cite this Detail-Document as follows: Antibiotic and antifungal use during pregnancy and breastfeeding.
Pharmacist’s Letter/Prescriber’s Letter 2009;25(6):250607.
Evidence and Advice You Can Trust…

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Detail-Document #250607

−This Detail-Document accompanies the related article published in−

Antibiotic and Antifungal Use During Pregnancy and Breastfeeding

Abbreviation: AAP=American Academy of Pediatrics; BSA=body surface area; GI=gastrointestinal; IV=intravenous.

Drug Pregnancy Use in Pregnancy Use in Lactation

Ampicillin B • See penicillin derivatives. • Excreted into breast milk in low

Drug Pregnancy Use in Pregnancy Use in Lactation

Cefadroxil B • See cephalosporins. • Excreted into breast milk in low

Drug Pregnancy Use in Pregnancy Use in Lactation

Cefazolin B • See cephalosporins. • Excreted into breast milk in low

Cefdinir B • See cephalosporins. • Cefdinir is expected to be excreted

Cefditoren B • See cephalosporins. • No human data.

Cefepime B • See cephalosporins. • Cefepime is excreted in human milk in

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Dicloxacillin B • See penicillin derivatives. • No human data.

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Kanamycin D • See aminoglycosides. • See aminoglycosides.

Drug Pregnancy Use in Pregnancy Use in Lactation

Linezolid C • No human data. • No human data.

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Minocycline D • See tetracyclines. • See tetracyclines.

Moxifloxacin C • See fluoroquinolones. • See fluoroquinolones.

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Ofloxacin C • See fluoroquinolones. • See fluoroquinolones.

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Drug Pregnancy Use in Pregnancy Use in Lactation

Tinidazole C • Limited human data. • The AAP classifies tinidazole as an

Tobramycin D • Human data suggest low risk.1 • See aminoglycosides.

Drug Pregnancy Use in Pregnancy Use in Lactation

a. FDA Categories for the use of medications in pregnancy:12

Users of this document are cautioned to use their own http://www.fda.gov/fdac/features/2001/301_preg.html

33. Product information for Lamisil. Novartis. East mts/sti_2006/pdf/408_Vaginal_Discharge.pdf.

Evidence and Advice You Can Trust…

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