Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Aminoglycosides
Amikacin
Gentamicin
Tobramycin
•
•
•
Not expected to increase risk of major congenital
malformations.
Monitor drug concentrations for efficacy as higher
doses may be needed during pregnancy.
Theoretical risk of ototoxicity and nephrotoxicity.
•
•
Considered safe during breastfeeding
Monitor nursing infant for GI symptoms.
Not expected to increase risk of major congenital
malformations.
Amoxicillin/clavulinic acid should be avoided in
women at risk of preterm delivery due to increased
risk of neonatal necrotising enterocolitis.
•
•
Considered safe during breastfeeding
Monitor nursing infant for GI symptoms.
Penicillins
Ampicillin
Cloxacillin ¹
Penicillin G
Amoxicillin/clavulinic acid
Piperacillin/tazobactam¹,²
•
•
Ticarcillin¹,²/clavulanic acid
2. Human data on ticarcillin and
piperacillin/tazobactam are limited;
however, penicillins as a class are
considered safe during breastfeeding.
1. Human data on cloxacillin, piperacillin/tazobactam,
and ticarcillin are limited; however, penicillins as a
class are considered safe during pregnancy.
Cephalosporins
Cefazolin
Ceftazidime
Ceftriaxone
Cefuroxime
Cephalexin
Cefepime
•
Not expected to increase risk of major congenital
malformations.
•
•
Considered safe during breastfeeding
Monitor nursing infant for GI symptoms.
The information in this table was prepared by Motherisk and is to be used for guidance purposes only.
For more information, please contact the Motherisk hotline Monday to Friday 9 AM to 5 PM.
Phone 416-813-6780. Fax 416-813-7562.
1
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Carbapenems
Ertapenem
Meropenem
•
•
No human data; however, there is no evidence of
increased risk of major congenital malformations
with other beta-lactam antibiotics.
Use when benefit outweighs unknown risk to the
fetus.
•
Not expected to increase risk of major congenital
malformations.
•
•
No human data; however, other betalactam antibiotics are not expected to
cause adverse effects in breastfed infants
Monitor nursing infant for GI symptoms.
Macrolides
Azithromycin
•
•
Clarithromycin
Erythromycin
•
•
Limited human data.
Not expected to increase risk of major congenital
malformations.
•
•
Not expected to increase risk of major congenital
malformations.
•
•
•
Not expected to cause adverse effects in
breastfed infants.
Monitor nursing infant for GI symptoms.
Not expected to cause adverse effects in
breastfed infants.
Monitor nursing infant for GI symptoms.
Not expected to cause adverse effects in
breastfed infants.
Monitor nursing infant for GI symptoms.
2
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Quinolones
Ciprofloxacin
•
Not expected to increase risk of major congenital
malformations.
•
•
Levofloxacin
Moxifloxacin *
•
•
Limited human data.
Not expected to increase risk of major congenital
malformations.
•
•
Limited human data; however, not
expected to cause adverse effects in
breastfed infants.
Monitor nursing infant for GI symptoms.
Limited human data; however, short-term
use is acceptable during breastfeeding.
Monitor nursing infant for GI symptoms.
* It would be preferable to use of a drug
other than moxifloxacin for which safety
information is available.
3
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Sulfonamides
Co-trimoxazole
(TMP + SMX)
(trimethoprim +
sulfamethoxazole)
•
•
•
•
Case control studies suggest an association with
neural tube defects (NTDs), cardiovascular
malformations and facial clefting as a result of
antifolate effect.
During 1st trimester, use of an alternate agent
would be preferable where feasible.
If use during the 1st trimester cannot be avoided,
high dose folic acid (4-5mg/day) should be given to
minimize the risk of NTDs.
Sulfamethoxazole should be avoided near term
due to potential toxicity to the newborn (hemolytic
anemia and kernicterus).
•
•
•
•
•
Trimethoprim is present at low levels in
breast milk and is not expected to cause
adverse effects in breastfed infants.
Sulfamethoxazole use during
breastfeeding is not expected to cause
adverse effects in healthy, full term
infants.
Sulfamethoxazole should be used with
caution while breastfeeding premature
infants or neonates with
hyperbilirubinemia.
Sulfamethoxazole should be avoided
while breastfeeding an infant with G6PD
deficiency.
Monitor nursing infant for GI symptoms.
4
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Tetracyclines
Doxycycline
Minocycline
Tetracycline
(see also Tigecycline
under “Miscellaneous
Antibacterial Agents”)
•
Should be avoided after 15 weeks of gestation due
to reports of possible discoloration of the deciduous
teeth.
•
•
•
•
•
Low levels in breast milk and reduced oral
bioavailability in the infant.
Short-term use is not expected to cause
adverse effects in breastfed infants.
Prolonged or repeated treatment courses
during nursing should be avoided
(theoretical precaution).
Monitor nursing infant for GI symptoms.
Black discoloration of breast milk has
been reported with minocycline.
Miscellaneous Antibacterial Agents
Clindamycin
•
Not expected to increase risk of major congenital
malformations.
•
Monitor nursing infant for possible
diarrhea, oral thrush, and for blood in the
stool suggestive of antibiotic-associated
colitis (rare).
Daptomycin
•
•
•
No human data on exposure during 1st trimester.
Animal studies show no evidence of fetal risk.
Should be used only when benefit outweighs
unknown risk to the fetus.
•
•
•
Limited human data.
Low oral bioavailability.
Not expected to cause adverse effects in
breastfed infants.
Monitor nursing infant for GI symptoms.
•
Linezolid
•
•
•
No human data.
An alternate agent with a known safety profile
would be preferred.
Should be used only when benefit outweighs
unknown risk to the fetus.
•
•
•
No human data.
An alternate agent with a known safety
profile would be preferred.
Monitor nursing infant for GI symptoms.
5
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Metronidazole
Pregnancy
•
•
Not expected to increase risk of major congenital
malformations.
The theoretical risk suggested by in vitro and
animal studies has not been observed in clinical
experience.
Breastfeeding
•
•
•
•
Nitrofurantoin
•
•
Rifampin
•
•
Tigecycline
•
•
•
Not expected to increase risk of major congenital
malformations.
There is a theoretical risk of hemolytic anemia in
newborns, particularly in those with G6PD
deficiency, who are exposed in utero to
nitrofurantoin close to delivery. If there is a
concern, an alternate agent should be used after
37 weeks of gestation.
•
Not expected to increase risk of major congenital
malformations.
Prenatal exposure to rifampin has been linked to
hemorrhagic disease of the newborn. Prophylactic
administration of vitamin K is recommended to
prevent this complication.
•
No reports on use during human pregnancy.
Tigecycline is structurally related to tetracycline
and thus should be avoided after 15 weeks of
gestation.
Use of an alternate agent with a known safety
profile would be preferred.
•
•
•
•
•
•
•
•
Not expected to cause adverse effects in
breastfed infants.
Infant dose via breast milk is lower than
therapeutic dose used in infants.
Some recommend discontinuing
breastfeeding (pump and discard milk) for
12 to 24 hours after single-dose (e.g., 2 g)
maternal treatment of Trichomonas
infection.
Monitor nursing infant for GI symptoms.
Use with caution when breastfeeding
infants under 1 month of age and those
with G-6-PD deficiency.
Not expected to cause adverse effects in
breastfed infants > 1 month old.
Monitor nursing infant for GI symptoms.
Limited information; however, amounts in
breast milk are low.
Breastfeeding should not be discouraged
in women taking rifampin.
Monitor nursing infant for GI symptoms.
No human data.
Low oral bioavailability.
Use of an alternate agent with a known
safety profile would be preferred.
Monitor nursing infant for GI symptoms.
6
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS
Name of Agent / Class
Vancomycin
Pregnancy
•
•
Limited human data.
Should be used only when benefit outweighs
unknown risk to the fetus.
Breastfeeding
•
•
Limited information; however, amounts in
breast milk and oral bioavailability are low.
Monitor nursing infant for GI symptoms.
7
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIFUNGAL AGENTS
Name of Agent / Class
Amphotericin B
Pregnancy
•
•
Caspofungin
•
•
•
Breastfeeding
Not expected to increase risk of major congenital
malformations.
Should be used only when benefit outweighs
unknown risk to the fetus.
•
•
•
No human data.
Low oral bioavailability.
Not expected to cause adverse effects in
breastfed infants.
No human data.
Embryotoxic in animal studies.
Should be avoided in 1st trimester, whenever
possible.
•
•
•
No human data.
Low oral bioavailability.
Not expected to cause adverse effects in
breastfed infants.
Monitor breastfed infant for symptoms of
histamine release.
Monitor breastfed infant for GI symptoms.
•
•
Fluconazole
•
•
Not expected to increase risk of major congenital
malformations when used in low-doses (150 mg)
for vaginal candidiasis.
There are case reports of congenital anomalies
with prolonged use in doses > 400 mg/day during
the 1st trimester. (Causation has not been proven).
•
•
Amounts found in breast milk are lower
than the neonatal fluconazole dose.
Considered safe during breastfeeding
Itraconazole
•
•
Limited human data.
Not expected to increase risk of major congenital
malformations.
•
•
No human data.
Use of an alternate agent with a known
safety profile would be preferred.
Pentamidine
•
•
Limited human data.
Can be considered when other agents have failed
and the benefit outweighs the unknown risk to the
fetus.
•
No human data.
8
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIFUNGAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Posaconazole
•
•
No human data.
Should be used only when benefit outweighs
unknown risk to the fetus.
•
No human data.
Voriconazole
•
•
No human data.
Animal studies have suggested voriconazole is
teratogenic and embryotoxic.
Should be avoided during pregnancy at least for
the 1st trimester unless other treatments have
failed and the benefit outweighs the unknown risk
to the fetus.
•
No human data.
•
9
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIVIRAL AGENTS
Name of Agent / Class
Pregnancy
Breastfeeding
Acyclovir / valacyclovir
•
Not expected to increase risk of major congenital
malformations.
•
•
Considered safe during breastfeeding.
Amounts found in breast milk are lower
than the neonatal acyclovir dosage.
Amantadine
•
•
Limited human data.
Case reports of congenital malformation with
exposure in pregnancy.
Use of an alternate antiviral agent with a known
safety profile would be preferred when possible.
•
•
•
No human data.
Suppresses prolactin production.
Use of an alternate antiviral agent with a
known safety profile would be preferred
when possible.
•
Famciclovir
•
Not expected to increase risk of major congenital
malformations, based on a small number of
exposures.
•
•
No human data.
Use of an alternate antiviral agent with a
known safety profile would be preferred
when possible.
Foscarnet
•
•
No human data in 1st trimester.
Case reports describe treatment in 2nd and 3rd
trimester with no adverse effects in the neonates.
Should be used only when the benefit outweighs
the unknown risk to the fetus.
Due to potential for renal toxicity, close follow up of
the fetus and monitoring of amniotic fluid volume
are recommended.
•
•
No human data.
Should be avoided during breastfeeding.
•
•
Ganciclovir / valganciclovir
•
•
Limited human data.
Should be used only when the benefit outweighs
the unknown risk to the fetus.
•
No human data.
Oseltamivir
•
Not expected to increase risk of major congenital
malformations.
•
Not expected to cause adverse effects in
breastfed infants.
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Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS
Name of Agent / Class
Artesunate
Pregnancy
•
•
Atovaquone / proguanil
•
•
•
Chloroquine
•
Breastfeeding
Limited human data, mostly on use in 2nd and 3rd
trimester.
Should be used only when the benefit outweighs
the unknown risk to the fetus.
•
•
No human data.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
Limited human data, mostly on use in 2nd and 3rd
trimester.
May be used to treat uncomplicated chloroquineresistant P. falciparum infection if:
o Other options are not available or not suitable
AND
o The benefit of its use outweighs the unknown
risk to the fetus.
Plasma concentrations of atovaquone and
proguanil were found in one study to be lower in
pregnant women due to an increase in clearance
and volume of distribution. It should be noted that
all women in this study were cured of their initial
infection in 1-3 days. Thus, the clinical significance
of those pharmacokinetic changes is unclear.
•
•
No human data.
Not expected to cause adverse effects in
breastfed infants weighing > 5 kg.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
Not expected to increase risk of major congenital
malformations.
•
•
•
Not expected to cause adverse effects in
breastfed infants.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
11
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS
Name of Agent / Class
Clindamycin
Pregnancy
•
•
Doxycyline
•
Breastfeeding
Not expected to increase risk of major congenital
malformations above the baseline risk in general
population.
Recommended for treatment of uncomplicated
chloroquine-resistant P. falciparum infection.
•
Should be avoided after 4-5 months of gestation,
due to reports of possible discoloration of the
deciduous teeth.
•
•
•
•
•
•
Primaquine
•
•
•
Should be used only when the benefit of its use
outweighs the unknown risk to the fetus.
Prophylactic administration of this drug should be
withheld until after delivery.
There is a theoretical risk of hemolytic anemia in a
G6PD-deficient fetus.
•
•
Monitor nursing infant for possible
diarrhea, oral thrush, and for blood in the
stool suggestive of antibiotic-associated
colitis (rare).
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
Low levels in breast milk and low oral
bioavailability in the infant.
Short-term use is not expected to cause
adverse effects in breastfed infants.
Prolonged or repeated treatment courses
during nursing should be avoided
(theoretical precaution).
Monitor nursing infant for GI symptoms.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
Not expected to cause adverse effects
when breastfeeding mothers and children
with normal G6PD levels.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
12
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS
Name of Agent / Class
Quinine
Pregnancy
•
•
Not expected to increase risk of major congenital
malformations when used in therapeutic doses.
Recommended for treatment of uncomplicated
chloroquine-resistant infection caused by
P. falciparum and P. vivax.
Breastfeeding
•
•
Not expected to cause adverse effects
when breastfeeding mothers and children
with normal G6PD levels.
The quantity of antimalarial drugs
transferred in breast milk is insufficient to
provide adequate protection against
malaria for the infant.
13
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents Appendix A
Dosage Adjustment in Pregnancy – General Considerations
Some of the physiological changes occurring in pregnancy may affect the pharmacokinetics of drugs taken during the gestational
period and postpartum. Depending on the clinical significance of these changes, adjustment of the dose and/or dosing interval may
warrant consideration. Below are some examples of altered drug distribution and elimination in pregnancy.
•
•
•
•
Increased maternal plasma volume may increase the volume of distribution of some drugs, which may require a dose increase.
Decreased plasma protein concentration, specifically albumin, may increase the free fraction of highly protein bound drugs, which
may require a dose reduction.
Increased renal blood flow and glomerular filtration rate may increase the elimination of drugs that are excreted primarily in the
urine. This may require use of an increased dose and/or a shorter dosing interval.
Alterations in the activity of hepatic drug metabolizing enzymes may require dosage adjustment as follows.
o Decreased activity (e.g., CYP1A2 and CYP2C19). For drugs that are dependent on these enzymes for elimination, a dose
reduction may be required. For drugs that require these enzymes for conversion to their active form, a dose increase may
be appropriate.
o Increased activity (e.g., CYP3A, CYP2D6 and CYP2C9). For drugs that are dependent on these enzymes for elimination,
a dose increase may be required. For drugs that require these enzymes for conversion to their active form, a dose
reduction may be required.
Note: there is a lack of pharmacokinetic data on which to base dosage adjustment of anti-infective agents in pregnancy, and there is
a lack of evidence demonstrating benefit. Accordingly, routine dosage adjustment is not practiced at SHSC.
14