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From The FDA: Cipro (Ciprofloxacin) Use by Pregnant and Lactating Women
Ciprofloxacin is approved for prophylaxis following inhalational
anthrax exposure. According to the Centers for Disease Control and
Prevention (CDC), ciprofloxacin (500 mg, orally, two times a day for 60
days) is the antibiotic of choice for initial prophylactic therapy among
asymptomatic pregnant women exposed to Bacillus anthracis. In
instances where the specific B. anthracis strain has been shown to
be penicillin-sensitive, prophylactic therapy with amoxicillin (500 mg,
orally, three times a day for 60 days) may be considered. CDC guidelines
for treatment of anthrax infection in pregnant women recommend either
ciprofloxacin or doxycycline with one or two other antibiotics added for
inhalational anthrax or systemic involvement.
While there are no controlled studies of ciprofloxacin use in pregnant
women to show safety, an expert review of published data on experiences
with ciprofloxacin use during pregnancy by TERIS - the Teratogen
Information System - concluded that therapeutic doses during pregnancy are
unlikely to pose a substantial teratogenic risk (quantity and quality of
data = fair), but the data are insufficient to state that there is no
risk. However, there are no human data available to assess the effects of
long-term therapy in pregnant women such as that proposed for treatment of
anthrax exposure. Ciprofloxacin is excreted into breast milk but is
considered as "usually compatible with breastfeeding" by the
American Academy of Pediatrics.
Background: The association between fluoroquinolones and
arthropathy, although observed in immature animals and rarely reported in
humans, has resulted in the restricted use of fluoroquinolones during
pregnancy. Young dogs given ciprofloxacin developed arthropathy with
permanent cartilage erosion in weight-bearing joints. Similar
arthropathies have been reported in neonatal mice. Transient arthropathy
has been reported in a small number of patients with cystic fibrosis,
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Arthropathy as a Teratogenic Effect
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- Animal reproduction studies have not shown arthropathy or
other musculoskeletal problems in offspring exposed to
ciprofloxacin in utero2.
- While no clinical studies have been conducted in pregnant
women, controlled prospective observational data suggest that in
utero exposure to fluoroquinolones is not associated with
clinically significant major musculoskeletal dysfunctions.
- Seven women exposed to ciprofloxacin during second or third
trimester delivered healthy normal babies. Motor, adaptive,
social, and language milestones in each child were consistent
with age, and no evidence of cartilage damage was found on
regular clinical assessments up to five years of age.
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Other Teratogenic Effects and Outcomes |
- Animal reproduction studies in mice, rats, and rabbits have
revealed no evidence of teratogenicity in offspring exposed to
ciprofloxacin in utero2. Studies in pregnant
monkeys did not produce detectable adverse effects on embryonic
or fetal development.
- Controlled prospective observational data on 200
fluoroquinolone-exposed human pregnancies (52.5% exposed to
ciprofloxacin and 68% treated during the first trimester) showed
the rate of major malformations among live-born children exposed
during the first trimester was in the expected normal range of 1
- 5% as was the rate in controls. There were no differences in
the rates of prematurity, spontaneous abortions, or birth weight9.
- Non-controlled prospective observational data on 70
ciprofloxacin-exposed human pregnancies (60% exposed during
the first trimester) showed the rate of congenital
malformations in live-born children exposed during the first
trimester was 4.7%. The frequencies of spontaneous
abortion/fetal death, post-natal disorders, prematurity and
intra-uterine growth retardation did not exceed background
rates.
- In a company-sponsored prospective registry of 116 human
pregnancies, 54% were exposed during the 1st trimester and
resulted in live births. Of these, six were malformed. There
was no pattern of anomalies seen among the reported spectrum
of minor and major malformations12.
- An observational cohort study looking at human experience with
five different antibiotics reported a total of 40 pregnancies
with ciprofloxacin. Five of the nine women who received
ciprofloxacin during the first trimester experienced normal
births with no reported congenital abnormalities. The other four
first trimester exposures were an ectopic pregnancy, a
spontaneous abortion and two terminations.
- One publication described six pregnant women exposed to longer
durations of ciprofloxacin therapy (3 weeks to 3months) who
delivered normal babies. There has also been a case report of a
pregnant woman exposed to three weeks of ciprofloxacin therapy
during early third trimester who delivered a normal baby.
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Duration of Exposure
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- The vast majority of reported experience with ciprofloxacin
during human pregnancy (as described above) is short-term, 1st
trimester exposure.
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Published - 14:00 UTC 08:00 EST 2-Nov-2001