Azithromycin in Pregnancy and Breastfeeding
      
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Azithromycin (Zithromax ®)
Azithromycin is an azalide antibiotic related to erythromycin. Molecular weight: 749.0

"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." [1]

Azithromycin appears to have limited transplacental transfer [2] in humans with high sustained levels within myometrium, adipose, and placental tissue [3].

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 [4]. There is one case 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[5].

In three additional case reports of pregnant women treated for scrub typhus the women 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 [9].

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 [12].

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 [13]. 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[14].

 

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 equation: 

Absorbed dose = Drug concentration in milk x Volume of milk consumed x Bioavailability

Where:

    Drug concentration in milk = 2.8 micrograms/mL
    Volume of milk consumed = 150 ml/kg/day (in this case the infant weighed 3.1 kg)
    Bioavailability = 37%
 Absorbed dose =  482 micrograms/day.

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.   [15].

SEARCH LITERATURE

1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004: 2684
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. PUBMED
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 105:882-889, 1998. PUBMED
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. PUBMED
6. Choi E-K, Pai H: Azithromycin therapy for scrub typhus during pregnancy. Clin Infect Dis 27:1538-1539, 1998. PUBMED
7. Bush MR, Rosa C Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy. Obstet Gynecol. 1994 ;84:61-3. PUBMED
8. Wehbeh HA, Single-dose azithromycin for Chlamydia in pregnant women. J Reprod Med. 1998;43:509-14. PUBMED
9. Adair CD, Gunter M, Stovall TG, McElvoy G, Veille JC, Erment JM. Chlamydia in pregnancy: a randomized trial of azithromycin and erithromycin. Obstet Gynecol 1998;91:165-8.PUBMED
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 PUBMED
11. 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. PUBMED
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. PUBMED
14. Cooper WO, Ray WA, Griffin MR. Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol. 2002;100:101-6. PUBMED
15. Kelsey JJ et al.Presence of azithromycin breast milk concentrations: a case report. Am J Obstet Gynecol. 1994;170:1375-6. PUBMED

Created: 11/27/2002
Last Update: 12/30/2003

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