INDICES> ciprofloxacin and metronidazole in first trimester (2)

["marceg@ull.es" <marceg@ull.es>]

INDICES> ciprofloxacin and metronidazole in first trimester (2)
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Dear Dr. Suresh:

I'm sorry but I haven't read your mail until today...

It's true  that these drugs are 'contraindicated' during pregnancy, because
there are alternative treatments more knowdlegdes to use in pregnancy women. But
also it's  true that these drugs are not associated with a major risk of
malformations than general population (both are FDA's pregnancy categories B or
C; you could use these drugs in a pregnant woman if you don't have
alternatives).

Metronidazole is not recomended during pregnancy because there is not
epidemiologic studies showing ausence of risk (FDA's pregnancy category tipe A),
but it's classificated as tipe B by the CDC and manufacturer (1). TERIS says:
"Magnitude of Teratogenic Risk: None to Minimal", 'but' "Quality and Quantity of
Data: Fair" (could be worst: None - Poor - Fair - Good -Excellent) (2):
- The frequency of maternal treatment with metroniadazole during first four
lunar months of pregnancy was no greater than expected among 4264 spontaneous
abortions or among 6564 infants with various birth defects, 984 infants with
cardiovascular defects, 122 infants with oral clefts, or 56 infants with spina
bifida in a Michigan Medicaid record linkage study (3).
- No increase in the frequency of congenital anomalies was seen among the
children of more than 200 women treated with metronidazole during the first
trimester of pregnancy in two cohorst of the Boston Collaborative Drug
Surveillance Program (4).

Manufacturing laboratories of ciprofloxacin and the Food and Drug Administration
(FDA) of the United States classify this drug in category C for their use during
pregnancy (1, 2, 4). That is, the use of ciprofloxacin during pregnancy does not
seem to be associate with an increase in the risk of mayor congenital
malformations, but there are no epidemiologic studies who discard it, and the
association of some alterations of occasional way takes to contraindicate its
use once knows that the patient is pregnant (1). The authors who have reviewed
the use of quinolons during pregnancy do not find associate an increase in the
risk of malformations (1).
- The data discussed on the toxicity of these drugs talk about to studies on
alterations in cartilage, bone, cristaluria, DNA damage, alterations in the
immune system, fetal toxicity and ocular toxicity, as much in the man as in
diverse species animals, having itself reached the conclusion that these effects
are species-employees (4): thus, for example, the damage to the cartilage of
growth in young animals has been seen in mice, rats, rabbits and marmotas, but
it has not been seen in innumerable species of monkeys, and it does not happen
in humans; in addition, have been cataracts subcapsular in dogs and rats that
received pefloxacin, but in monkeys rhesus not receiving ciprofloxacin. The
associated oftalmologic toxicity to the administration of fluorquinolons in
humans is occasional.
- The studies on mutagenic capacity have analyzed the union "in vitro " of
fluorquinolons to the human DNA and have concluded that this capacity is not
translated in an increase of mutagenicity, DNA damage  or carcinogenicity: they
have been negative for ciprofloxacin, enoxacin, fluroxacin, norfloxacin and
temafloxacin, was only positive for high doses of pefloxacin. Any alteration
throughout the studies made in animals has not been observed, and there is
evidence of these no findings in humans (4).
- Therapeutic Base of the Karolinska Institute (Drug-line) has eight
consultations on the risks of this drug during pregnancy, and establish that the
processing with Norfloxacin during the first months of the pregnancy does not
increase the risk of malformations and it's not indication to abort (5).

References:
1. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. Williams
and Wilkins ed. 5th ed. Baltimore, 1998: 722-6 (metroniadazole); 210-4
(ciprofloxacin).
2. Friedman JM, Polifka JE. Teratogenic Effects of Drugs a Resource for
Clinicians (TERIS). The Johns Hopkins University Press. Baltimore and London
1994: 405-6 (metronidazole); 130-1 (ciprofloxacin).
3. Rosa FW, Baum C, Shaw M. Pregnancy ourcomes after first-trimester vaginits
drug therapy. Obstet Gynecol, 1987; 69: 751-5.
4. Jick H, Holmes L.B, Hunter J.R, et al. First-trimester drug use and
congenital disorders. JAMA, 1981; 246: 343-6.
4. Gilstrap LC, Little BB. Antimicrobial Agents during Pregnancy. In: Gilstrap
LC, Little BB (eds). Drugs and Pregnancy. 2nd ed. Chapman & Hall. New York,
1998: 52-57 (quinolones).
5. Base de Consultas Terapéuticas DRUGLINE. Servicio de Farmacología Clínica.
Hospital Huddinge. Instituto Karolinska. Estocolmo (Suecia). Consultas Nº: 9803,
9145, 7848, 7315, 7229, 6705, 5961, 5939. (marzo, 1994)


(I hope you'll excuse my englihs)

Marcelino García Sánchez-Colomer. MD PhD
and Eduardo Fernández Quintana. PD. PhD
Drug Surveillance and Therapeutic Information
of Canary Islands
University of La Laguna
TENERIFE
Spain

Email: marceg@ull.es


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