Subject: http://www.fda.gov/cder/drug/infopage/cipro/cipropreg.htm
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,
Arthropathy as a Teratogenic Effect
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.
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 weight.
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 malformations.
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 3 months) 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.
Duration of Exposure
The vast majority of reported experience with ciprofloxacin during human
pregnancy (as described above) is short-term, 1st trimester exposure.
Prepared by the Pregnancy Team, Food and Drug Administration 10/30/01
Forwarded by:
Frank J. Nice, DPA, CPHP
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