| |
Doxycycline (Vibramycin, Monodox, Doryx, Doxy, Atridox, Periodox, Vibra-Tabs) Use By Pregnant And Lactating Women
Doxycycline is approved for the treatment of anthrax. 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. Doxycycline should be used for prophylaxis only when there are
contraindications to the use of other appropriate antibiotics. 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 doxycycline use in pregnant
women to show safety, an expert review of published data on experiences
with doxycycline 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 =
limited to fair), but the data are insufficient to state that there is no
risk. The risk of cosmetic staining of the primary teeth by doxycycline is
undetermined (quantity and quality of data = very limited)4.
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. Doxycycline is excreted into breast milk. Short-term use by
lactating women is not necessarily contraindicated, however, the effects
of prolonged exposure to doxycycline in breast milk are unknown.
Background: The use of doxycycline during pregnancy has
historically been discouraged unless other drugs are not likely to be
effective or are contraindicated1. This is due to the knowledge
that tetracyclines cause cosmetic staining of the primary dentition in
fetuses exposed during the second or third trimester of pregnancy,
and manufacturer concerns about possible enamel hypoplasia and depression
of fetal bone growth1.
|
Adverse Effects on Fetal Teeth and Bones |
- There have been no published human data showing that fetal
exposure to doxycycline causes cosmetic staining of the primary
teeth, however this cannot be ruled out because of the
tetracycline class effect. The concern about enamel hypoplasia
and caries with in utero exposure to tetracycline has
been shown to not be related,.
- While not reported with doxycycline or with in utero
exposure, oral tetracycline given to premature infants has been
associated with a decrease in fibular growth that was reversible
when the drug was discontinued.
- While there have been no reports in humans, an increased
frequency of skeletal anomalies associated with maternal
toxicity was seen among the offspring of pregnant mice, but not
rabbits, treated with 17 times the maximum human dose of
doxycycline.
|
|
Other Teratogenic Effects and Outcomes
|
- A case-control study (18,515 mothers of infants with
congenital anomalies and 32,804 mothers of infants with no
congenital anomalies) shows a weak but marginally statistically
significant association with total malformations and use of
doxycycline anytime during pregnancy. (Sixty-three (0.19%) of
the controls and 56 (0.30%) of the cases were treated with
doxycycline.) This association was not seen when the analysis
was confined to maternal treatment during the period of
organogenesis (i.e., in the second and third months of
gestation) with the exception of a marginal relationship with
neural tube defect based on only two exposed cases. The authors
thought the significant difference with total malformations
could be attributed to recall bias.
- A small prospective study of 81 pregnancies describes 43
pregnant women treated for 10 days with doxycycline during
early first trimester. All mothers reported their exposed
infants were normal at 1 year of age.
- A non-peer-reviewed surveillance study of Medicaid recipients
involving 229,101 completed pregnancies reported that data on
1,795 doxycycline-exposed pregnancies did not support an
association between doxycycline and any of the six specific
malformations evaluated (i.e., cardiovascular defects, oral
clefts, spina bifida, polydactyly, limb reduction defects, and
hypospadias) .
- Unpublished data from an ongoing case-control study reports 34
first trimester exposures to doxycycline among mothers of
malformed infants, with no apparent clustering of categories or
specific defects.
- With the exception of skeletal anomalies (see above), the
frequency of malformations was not increased with doxycycline
exposure during pregnancy among the offspring of mice or
rabbits, but at the highest dosage level decreased fetal
weight (mice and rabbits), and increased fetal death (rabbits)
were seen in association with maternal toxicity11.
- No teratogenic effects occurred among the offspring of
pregnant mice, rats, or rabbits given about 100 times the
usual human dose of doxycycline. Another study found no
teratogenicity with doxycycline exposure in rats, rabbits, or
monkeys.
|
|
Maternal Liver Toxicity
|
- While there are no published reports with doxycycline use,
tetracycline use has been associated with fatty liver of
pregnancy,. This rare but often fatal disorder has
been reported to follow high dose intravenous tetracycline use
to treat pyelonephritis.
|
|
Duration of Exposure
|
- The vast majority of reported experience with doxycycline
during human pregnancy (as described above) is short-term, first
trimester exposure.
|
|
|
Published - 14:00 UTC 08:00 EST 2-Nov-2001