http://www.fda.gov/cder/drug/infopage/cipro/cipropreg.htm
Ciprofloxacin is approved for prophylaxis
following inhalational anthrax exposure1.
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 considered2. 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 involvement3.
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 risk4.
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.5
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 mice6.
Transient arthropathy has been reported in a small number of patients with
cystic fibrosis7,8
|
Arthropathy
as a Teratogenic Effect |
ˇ Animal reproduction studies have not shown
arthropathy or other musculoskeletal problems in offspring exposed to
ciprofloxacin in utero2. ˇ 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 dysfunctions9. ˇ 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 age10. |
|
Other
Teratogenic Effects and Outcomes |
ˇ 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 development11. ˇ 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. ˇ 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 rates12. ˇ 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. |
|
Other
Teratogenic Effects and Outcomes (cont'd) |
ˇ 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 terminations13. ˇ One publication described six pregnant women
exposed to longer durations of ciprofloxacin therapy (3 weeks to 3 months)
who delivered normal babies14.
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
baby15. |
|
Duration
of Exposure |
ˇ 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
1 Product information CiproŽ, 2001
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2 Notice to readers: Updated recommendations for antimicrobial prophylaxis
among asymptomatic pregnant women after exposure to Bacillus anthracis. MMWR
2001;50(43):960.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5043a5.htm
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3 Update: Investigation of bioterrorism-related anthrax and interim
guidelines for exposure management and antimicrobial therapy, October 2001. MMWR
2001;50(42);909-919 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5042a1.htm.
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4 Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A
Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins
University Press; 2000:149-195.
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5 Committee on Drugs, American Academy of Pediatrics. The transfer of
drugs and other chemicals into human milk. Pediatrics.
2001;108(3):776-789.
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6 Linseman DA, Hampton LA, and Branstetter DG. Quinolone-induced
arthropathy in the neonatal mouse: Morphological analysis of articular lesions
produced by pipemidic acid and ciprofloxacin. Fundam Appl Toxicol
1995;28:59-64.
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7 SamuelsonWM, Pleasants RA, and Whitaker MS. Arthopathy secondary to ciprofloxacin
in an adult cystic fibrosis patient. Ann Pharmacother 1993;27:302-303.
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8 Jawad ASM. Cystic fibrosis and drug-induced arthropathy. Br J
Rheumatol 1989;28(2):179-180.
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9 Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following
gestational exposure to fluoroquinolones: a multicenter prospective controlled
study. Antimicrob Agents Chemother 1998:42(6)
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10 Koul PA, Wani JI, Wahid A. Ciprofloxacin for multiresistant
enteric fever in pregnancy. Lancet 1994;84:535-538.
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11 Schluter G. Ciprofloxacin: toxicological evaluation of
additional safety data. Am J Med 1989;87:5A(37s)-5A(39s).
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12 Schaefer C, Amoura-Elefant E, Vial T, et al. Pregnancy outcome
after prenatal quinolone exposure. Evaluation of a case registry of the
European Network of Teratology Information Services (ENTIS). Eur J Obstet
Gynecol Reprod Biol 1996;69:83-89.
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13 Wilton LV, Pearce GL, and Mann RD. A comparison of
ciprofloxacin, norfloxacin, ofloxacin, azithromycin and cefixime examined by
observational cohort studies. Br J Clin Pharmacol 1996;41:277-284.
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14 Bomford JAL, Ledger JC, O'Keeffe BJ, and Reiter C. Ciprofloxacin
use during pregnancy. Drugs 1993;45 (Suppl 3):461-462
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15 Ludlam H, Wreghitt TG, Thornton S, et al. Q Fever in
pregnancy. J Infect 1997;34:75-78.
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