Pharmacology and toxicology
Macrolides inhibit bacterial protein synthesis and have bacteriostatic properties. Erythromycin is the oldest of the macrolides. Azithromycin, clarithromycin, dirithromycin, josamycin, mide-camycin, oleandomycin, and roxithromycin are newer macrolides. Azithromycin belongs to the azalides, a new class of macrolides which resemble erythromycin but have different pharmacokinetic profiles and antibacterial activity. The newer macrolides have a longer half-life and fewer gastrointestinal side effects.
Little is known about the pharmacokinetics in pregnant women. Maternal and fetal serum levels are low and may vary; fetal plasma concentrations are 5-20% of maternal plasma concentrations. In a study using in vitro perfusion of placentas at term, Heikkinen (2000) found that the transplacental transfer of the macrolides erythromycin, roxithromycin, and azithromycin was relatively low (<5%). In patients scheduled for elective cesarean section who were given azithromycin 6-168 hours before the procedure, high placental levels were found. Fetal serum levels of azithromycin, however, were low (Ramsey 2003). Data from a recent study suggest that in patients who arc treated in the third trimester, gastrointestinal absorption of erythromycin may be delayed; severe adverse gastrointestinal events may forewarn of subtherapeutic plasma concentrations which could have consequences for the treatment outcome (Larsen 1998).
Erythromycin has always been considered a safe and effective antibiotic during pregnancy, Data on more than 7000 first-trim ester exposures do not support an association between erythromycin and congenita! malformations (Briggs 2005, Czeizel 1999). in a recent study, however, Kailen (2005) reported an increased rate of cardiovascular malformations (1.8%), especially ventricular and atrial septal defects. They conclude that even if the association is causal, the individual risk for an infant is still low. The same authors also found an increased incidence of pyloric stenosis (0.2%). Louik (2002), on the contrary, did not find an increased risk of pyloris stenosis as did Cooper (2002), but the last publication reports a possible association with other macrolides. The association between prenatal exposure to erythromycin and other macrolides and infant pyloric stenosis is still uncertain.
Erythromycin estolate and troleandomycin may adversely influence maternal liver function; hepatotoxicity is especially seen in the second half of pregnancy, and is reversible. Fetal development is not impaired in such cases (Lewis 1991, McCormack 1977).
Available data on the newer macrolides are still limited. Several studies are available on the pregnancy outcome after clarithromycin exposure. Cardiovascular malformations have been reported in rat species after prenatal exposure to clarithromycin, but so far no evidence exists that prenatal exposure in the human docs increase the rate of cardiovascular or other major malformations (Drinkard 2000, Einarson 1998, Schick 1996). Einarson (1998) found only a significantly higher rate of spontaneous abortions in the exposed group (122 first-trimester exposures), which might be due to confounding factors such as maternal diseases.
Spiramycin is recommended during pregnancy for the treatment of maternal toxoplasmosis to prevent congenital toxoplasmosis. Adverse effects have not been reported.
Recommendation. Erythromycin is still the drug of choice among the macrolides during pregnancy. Erythromycin estolate and troleandomycin should not be given in the second and third trimesters. Newer macrolides such as azithromycin, clarithromycin, josamycin, and roxithromycin are second-choice macrolides. Spiramycin is the drug of choice for the treatment of toxoplasmosis during the first trimester.
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A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.