Azithromycin is an azalide antibiotic related to erythromycin. Molecular
"Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic dose concentrations (i.e., 200 mg/kg/day). These doses, based on a mg/m 2 basis, are estimated to be 4 and 2 times, respectively, the human daily dose of 500 mg. In the animal studies, no evidence of harm to the fetus due to azithromycin was found." 
Azithromycin appears to have limited transplacental transfer  in humans with high sustained levels within myometrium, adipose, and placental tissue .
Reports on the use of azithromycin during the first trimester in
human pregnancy are scarce.
The preponderance of the literature describes the use of azithromycin
during the second and third trimesters of pregnancy.
In an observational study of newly
marketed drugs prescribed in England azithromycin was taken during the first trimester in
eleven pregnancies. One patient chose to have an elective abortion. The
remaining mothers delivered ten normal infants . There is
report of a woman treated with oral azithromycin at approximately 3 weeks' gestation
for acute scrub typhus. She subsequently miscarried three weeks after
treatment. This individual had a history of two previous spontaneous
abortions. Her underlying illness and obstetrical history may have been
contributing factors leading to her miscarriage.
In three additional case reports of pregnant women treated for scrub typhus
were treated with azithromycin between 19 and 24 weeks’
gestation. Two of these women had given birth at term to healthy infants
at one year follow up and one woman was lost to follow up [5,6] .
Azithromycin has also been used to successfully treat Chlamydia during the second and third trimesters of pregnancy
(using a single 1 gram oral dose) [7-11]. Primary outcomes reported for most studies were success of treatment and
maternal side effects. No adverse neonatal outcomes were specifically
reported by one study of 42 pregnancies .
A single 1 gram oral dose of azithromycin
was ineffective in reducing lower genital colonization of Ureaplasma
urealyticum in women with preterm labor or preterm premature rupture of
membranes (PROM) between 22 and 34 weeks' gestation .
In a retrospective study Mahon BE, et al reported a higher incidence of
infantile hypertrophic pyloric stenosis in the infants of mothers who had
used macrolide (erythromycin, azithromycin, and clarithromycin) antibiotics
during the last ten weeks of pregnancy. However, the data did not
reach statistical significance . Cooper WO et. al. reviewed
the files of 260,799 mother/infant pairs enrolled in the Tennessee Medicaid/TennCare
from 1985-1997. For nonerythromycin macrolide use at any time during
pregnancy, there was an association of pyloric stenosis with maternal non
erythromycin macrolide prescriptions; odds ratio of 2.77. Nonerythromycin macrolides included lincomycin, clindamycin,
clarithromycin, azithromycin, and dirithromycin.
BREAST FEEDING: Azithromycin appears to be excreted into human milk.
In one case report
a mother took an initial dose of 1 gram of oral azithromycin. Approximately
60 hours later she resumed taking azithromycin at a dose of 500 mg daily for an
additional three doses. One hour after the first 500 mg dose the breast
milk concentration of azithromycin was 1.3
micrograms/mL. Thirty hours after the third dose of 500 mg the breast milk
concentration was 2.8
micrograms/mL. Maternal serum levels were not included in the report.
The predicted dose of azithromycin to the infant was calculated from the
Absorbed dose = Drug concentration in milk x Volume of milk consumed x
Drug concentration in milk = 2.8 micrograms/mL
Absorbed dose = 482 micrograms/day.
Volume of milk consumed = 150 ml/kg/day (in this case the infant weighed 3.1
Bioavailability = 37%
The authors of the report concluded that azithromycin appears to
accumulate in breast milk. However, this may not be clinically significant
given the low dose delivered to the infant. .
1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR;
2. Heikkinen T,et. al., The
transplacental transfer of the macrolide antibiotics erythromycin,
roxithromycin and azithromycin. BJOG. 2000;107:770-5. PUBMED
3. Ramsey PS,et. al., Maternal
and transplacental pharmacokinetics of azithromycin.
Am J Obstet Gynecol. 2003;188:714-8.
4. Wilton LV, Pearce GL,
Martin RM et al: The outcomes of pregnancy in women exposed to newly
marketed drugs in general practice in England. Br J Obstet Gynaecol
5. Watt G, et al. Azithromycin activities against Orientia tsutsugamushi strains
isolated in cases of scrub typhus in Northern Thailand.
Antimicrob Agents Chemother. 1999;43:2817-8.
6. Choi E-K, Pai H: Azithromycin therapy for scrub typhus during pregnancy.
Clin Infect Dis 27:1538-1539, 1998.
7. Bush MR, Rosa C Azithromycin and erythromycin in the treatment of
cervical chlamydial infection during pregnancy.
Obstet Gynecol. 1994 ;84:61-3.
8. Wehbeh HA, Single-dose azithromycin for Chlamydia in pregnant women.
J Reprod Med. 1998;43:509-14.
9. Adair CD, Gunter M, Stovall TG, McElvoy G, Veille JC, Erment JM. Chlamydia
in pregnancy: a randomized trial of azithromycin and erithromycin. Obstet
10. Jacobson GF, A randomized
controlled trial comparing amoxicillin and azithromycin for the treatment of
Chlamydia trachomatis in pregnancy.
Am J Obstet Gynecol. 2001;184:1352-4
Kacmar J,et al. ,A randomized trial of azithromycin versus amoxicillin for
the treatment of Chlamydia trachomatis in pregnancy.
Infect Dis Obstet Gynecol. 2001;9(4):197-202. PUBMED
12. Ogasawara KK and Goodwin TM
Efficacy of azithromycin in reducing lower genital Ureaplasma urealyticum
colonization in women at risk for preterm delivery. J Matern Fetal Med. 1999 ;8:12-6.
13. Mahon BE, Rosenman MB, Kleiman MB.
Maternal and infant use of erythromycin and other macrolide
antibiotics as risk factors for infantile hypertrophic pyloric stenosis.
J Pediatr. 2001;139:380-4.
14. Cooper WO, Ray WA, Griffin MR. Prenatal prescription of macrolide
antibiotics and infantile hypertrophic pyloric stenosis.
Obstet Gynecol. 2002;100:101-6.
15. Kelsey JJ et al.Presence of azithromycin breast milk
concentrations: a case report.
Am J Obstet Gynecol. 1994;170:1375-6.
Last Update: 12/30/2003