Azithromycin
MedicationZ-Pak, Zithromax, Zmax
Antibiotic
Research strength: 3 / 5
MotherToBaby reports that most studies have not found an increased chance of birth defects with azithromycin, although a few suggested some defects, and most studies have not reported increased miscarriage. The MHRA says early-pregnancy data cannot confirm or rule out a small increase; its review cites one moderate-bias miscarriage study, while a later cohort did not find an association for macrolides overall or specific medicines. A 2025 French cohort found no increase in major defects overall for macrolides but reported small signals for spina bifida and syndactyly at the class level; the azithromycin-specific spina bifida estimate was imprecise. The ZITHROMAX label says decades of published and postmarketing data did not identify drug-associated risks but notes limits in observational research. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby - Azithromycin (Z-Pak)Teratology service
- MHRA - Safety of macrolide antibiotics in pregnancyUK government
- Muanda et al. - Spontaneous abortion cohort studyUS government
- Hegger et al. - Macrolides and spontaneous abortionUS government
- Tran et al. - French nationwide macrolide cohortUS government
- DailyMed - Pfizer ZITHROMAX prescribing informationDrug company label
Research strength: 3 / 5
MotherToBaby says azithromycin is not expected to increase preterm delivery or low birth weight, but it gives no separate second-trimester estimate. A 2021 review of 14 trials involving 17,594 participants, mostly malaria-prevention regimens, found lower rates of both outcomes versus controls, but its authors said application outside malaria-endemic settings is unclear. The MHRA review covers early pregnancy and does not provide a second-trimester estimate. A 2020 UK study found no increased risk of major malformations for macrolides in the second to third trimesters, but it was class-level and could not analyze azithromycin separately because few events occurred. A 2026 azithromycin-specific cohort found no significant increase in overall neurodevelopmental disorders compared with unexposed children across exposure periods. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby - Azithromycin (Z-Pak)Teratology service
- MHRA - Safety of macrolide antibiotics in pregnancyUK government
- Hume-Nixon et al. - Azithromycin perinatal outcomes reviewUS government
- Fan et al. - UK pregnancy and child outcomes cohortUS government
- Otoo et al. - Prenatal azithromycin and neurodevelopmentUS government
- DailyMed - Pfizer ZITHROMAX prescribing informationDrug company label
Research strength: 3 / 5
MotherToBaby says azithromycin is not expected to increase preterm delivery or low birth weight, but gives no separate third-trimester estimate. A 2021 review of 14 trials involving 17,594 participants, mostly malaria-prevention regimens, found lower rates of both outcomes versus controls, but its authors said application outside malaria-endemic settings is unclear. A 2020 UK study of 8,632 macrolide-exposed children, not azithromycin alone, found no significant association with ADHD or autism. A 2026 US cohort with 742 azithromycin-exposed children found no significant difference in overall neurodevelopmental-disorder risk versus unexposed children in any exposure period. The French birth-defect cohort examined first-trimester exposure, and the reviewed studies do not provide a separate azithromycin-specific third-trimester malformation estimate. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby - Azithromycin (Z-Pak)Teratology service
- Hume-Nixon et al. - Azithromycin perinatal outcomes reviewUS government
- Fan et al. - UK pregnancy and child outcomes cohortUS government
- Otoo et al. - Prenatal azithromycin and neurodevelopmentUS government
- Tran et al. - French nationwide macrolide cohortUS government
Azithromycin — Breastfeeding
Research strength: 4 / 5
MotherToBaby and LactMed say azithromycin passes into milk in small amounts; LactMed says adverse effects are not expected at these levels but advises watching for vomiting, diarrhea, or thrush. MotherToBaby notes that some studies suggested pyloric stenosis, a narrowing at the stomach outlet, when exposure occurred in the first two weeks, while other studies did not, and says the evidence is not enough to decide. NHS SPS says macrolides can be used with precautionary infant monitoring and describes conflicting pyloric-stenosis evidence. A 2019 review of two breastfeeding-exposure studies found no statistically significant association, but its estimate was imprecise and did not isolate azithromycin well. Ask your provider about your situation.
Last reviewed: 2026-10-16
Sources
- MotherToBaby - Azithromycin (Z-Pak)Teratology service
- LactMed - AzithromycinUS government
- NHS Specialist Pharmacy Service - Macrolides during breastfeedingUK government
- Sutton et al. - Azithromycin milk transfer after cesarean prophylaxisUS government
- Almaramhy and Al-Zalabani - Pyloric stenosis meta-analysisUS government
Pregnancy
Muanda et al. (2017) reported an adjusted OR of 1.65 (95% CI 1.34-2.02; 110 azithromycin-exposed miscarriage cases) in a nested case-control study; the MHRA review reports a 1.91 estimate versus penicillin from this study and judged it moderate risk of bias. Hegger et al. (2024) studied 65,457 pregnancies, including 825 macrolide-exposed, and found no association for macrolides overall or specific medicines (overall adjusted HR 1.00, 95% CI 0.77-1.31). Hume-Nixon et al. (2021) meta-analyzed 14 trials involving 17,594 participants, mostly malaria-prevention regimens, and found lower rates of low birth weight (pooled RR 0.79, 95% CI 0.68-0.93) and prematurity (RR 0.87, 95% CI 0.78-0.98) versus controls; the authors said generalizability outside malaria-endemic settings is unclear. Tran et al. (2025) compared 140,708 first-trimester macrolide exposures with 592,652 amoxicillin exposures and found no increase in major malformations overall (aRR 1.00, 95% CI 0.96-1.05), while identifying class-level spina bifida and syndactyly signals; the azithromycin-specific spina bifida estimate was imprecise (aRR 1.58, 95% CI 0.80-3.10). Fan et al. (2020) included 8,632 macrolide-exposed children in a cohort of 104,605 and found no association with four neurodevelopmental outcomes, while Otoo et al. (2026) included 742 azithromycin-exposed dyads among 15,527 and found no significant increase in overall neurodevelopmental disorders versus unexposed children in any exposure period.
Breastfeeding
LactMed summarizes small milk-transfer studies and reports that azithromycin was measured in milk after maternal oral and intravenous doses; published infant serum levels were not found in its 15 Dec 2025 revision. Sutton et al. (2015) studied 30 women receiving intravenous azithromycin before cesarean delivery; milk samples from 8 breastfeeding participants showed drug remained detectable up to 48 hours. Salman et al. (2015) measured milk from 20 Gambian women after a single 2 g oral dose during labor and modeled a median cumulative infant dose of 4.5 mg/kg (95% prediction interval 0.6 to 7.0) and a median relative cumulative dose of 15.7% (2.0% to 27.8%). LactMed's summary of that cohort gives 3.9 mg/kg and 2.2% weight-adjusted dosage; these are modeled estimates using different dose metrics. Almaramhy and Al-Zalabani (2019) included 14 reports in their review; only two studies addressed exposure through breastfeeding, with a pooled OR of 1.31 (95% CI 0.42-4.1), which was not statistically significant. Much of the pyloric-stenosis evidence concerns macrolides as a class and does not isolate azithromycin received through milk.
MotherToBaby describes azithromycin as a macrolide antibiotic and lists Z-Pak, Zithromax, and Zmax as brand names. The reviewed Pfizer label is specifically for ZITHROMAX tablets containing azithromycin.
What was tested
Pregnancy evidence includes observational cohorts, a nested case-control study, and regulator reviews; most outcomes were based on prescriptions and health records rather than randomized exposure. The 2025 French cohort assessed first-trimester macrolide-class exposure and individual medicines, but its malformation analyses included pregnancies linked to live-born infants. The 2026 neurodevelopment cohort assessed 15,527 mother-infant dyads, including 742 azithromycin-exposed children, with a mean follow-up of 5.5 years. Breastfeeding evidence includes small maternal milk-level studies and observational pyloric-stenosis studies; published infant azithromycin levels were not available in LactMed's 2025 revision.
First-trimester birth-defect findings
- Source A says
- MotherToBaby reports that most studies have not found an increased chance of birth defects. Andersson et al. found no significant increase in major birth defects with macrolide exposure compared with penicillin or other comparison groups. (MotherToBaby - Azithromycin (Z-Pak), Andersson et al. - Macrolides and major birth defects)
- Source B says
- Fan et al. found a first-trimester macrolide-class association with major and cardiovascular malformations versus penicillin. Tran et al. found class-level signals for spina bifida and syndactyly, although neither remained significant after multiple-comparison adjustment and the azithromycin-specific estimates were imprecise. (Fan et al. - Macrolide prescribing during pregnancy and child outcomes, Tran et al. - First-trimester macrolides and congenital malformations)
- Why they differ
- Studies used different populations, comparison groups, and outcome definitions. Some findings concern macrolides as a class rather than azithromycin alone; the newer signals involve relatively few outcomes and remain exploratory.
- What the evidence shows overall
- The available studies do not show an overall increase in major malformations, but they do not resolve every uncommon outcome. The class-level signals and the imprecise azithromycin estimates warrant clear uncertainty rather than a single settled conclusion.
Miscarriage findings
- Source A says
- MotherToBaby says most studies have not reported an increased chance of miscarriage. Hegger et al. found no association for macrolides overall or specific medicines in its cohort. (MotherToBaby - Azithromycin (Z-Pak), Hegger et al. - Exposure to macrolides during pregnancy and spontaneous abortions)
- Source B says
- Muanda et al. reported an association for azithromycin in one nested case-control study. The MHRA described the evidence as one moderate-bias study and said it could not establish the strength of the association. (Muanda et al. - Use of antibiotics during pregnancy and risk of spontaneous abortion, MHRA - Safety of macrolide antibiotics in pregnancy)
- Why they differ
- The findings come from different populations and study designs. The positive result is based on one observational study, and the MHRA noted concerns about selective reporting and residual confounding; the later cohort reported no association.
- What the evidence shows overall
- The evidence is mixed. The observed association is not proof that azithromycin caused pregnancy loss, and the later null cohort does not eliminate the possibility of a small association.
Pyloric stenosis after exposure through breast milk
- Source A says
- MotherToBaby reports that some studies suggested a possible increase when maternal use occurred in the first two weeks, while other studies did not. NHS SPS also says findings for macrolides are conflicting. (MotherToBaby - Azithromycin (Z-Pak), NHS Specialist Pharmacy Service - Using macrolide antibiotics during breastfeeding)
- Source B says
- Almaramhy and Al-Zalabani found no statistically significant association in the two studies that assessed exposure through breastfeeding, but the estimate was imprecise. (Almaramhy and Al-Zalabani - Macrolide exposure and pyloric stenosis meta-analysis)
- Why they differ
- The evidence is sparse, often describes macrolides as a group, and does not consistently identify which drug the mother used or distinguish milk exposure from other infant exposures.
- What the evidence shows overall
- The evidence does not establish an azithromycin-specific effect from breast milk. The limited data support describing the possible early-infant concern and the conflicting findings without treating either as settled.
- The MHRA says a macrolide can be used during pregnancy when the prescriber judges that treatment benefits outweigh possible risks and no suitable alternative is available. (MHRA)
- The EMA's 2025 review recommends aligning systemic azithromycin use with the revised approved indications and local resistance information to limit antimicrobial resistance. (European Medicines Agency)
- NHS SPS says macrolides can be used during breastfeeding with precautionary infant monitoring; its recommendations apply to full-term, healthy infants. (NHS Specialist Pharmacy Service)
General research, not specific to pregnancy.
The ZITHROMAX label describes QT prolongation and torsades de pointes, a potentially life-threatening heart rhythm problem, and reports an approximately two-fold short-term potential increase in cardiovascular death in observational studies. The MHRA reports more heart-related side effects when azithromycin was combined with hydroxychloroquine than when amoxicillin was used with hydroxychloroquine. EMA's 2025 review revised systemic-use information and added an antimicrobial-resistance warning.
- The ZITHROMAX label describes QT prolongation and postmarketing reports of torsades de pointes; it also reports an approximately two-fold potential short-term cardiovascular-death risk in observational studies and notes that causation is not established. (DailyMed - Pfizer ZITHROMAX prescribing information)
- The MHRA says people taking hydroxychloroquine with azithromycin were more likely to have heart-related side effects within 30 days than people taking hydroxychloroquine with amoxicillin. (MHRA - Hydroxychloroquine or chloroquine with macrolides: cardiovascular safety review)
- The EMA recommended a warning that azithromycin use can contribute to antimicrobial resistance because drug levels decline slowly after treatment ends. (European Medicines Agency - Azithromycin systemic-use referral)
- The ZITHROMAX label lists contraindications for known hypersensitivity to azithromycin or related macrolides and for prior azithromycin-associated cholestatic jaundice or hepatic dysfunction. (DailyMed - Pfizer ZITHROMAX prescribing information)
- MotherToBaby - Azithromycin (Z-Pak)Teratology serviceSecondary
- LactMed - AzithromycinUS governmentSecondaryPage dated 2025-12-15
- MHRA - Safety of macrolide antibiotics in pregnancyUK governmentSecondaryPage dated 2021-06-28Independent check
- MHRA - Hydroxychloroquine or chloroquine with macrolides: cardiovascular safety reviewUK governmentSecondaryPage dated 2022-02-15Independent check
- NHS Specialist Pharmacy Service - Using macrolide antibiotics during breastfeedingUK governmentSecondaryPage dated 2024-03-26Independent check
- European Medicines Agency - Azithromycin systemic-use referralEU agencySecondaryPage dated 2025-10-21Independent checkEuropean guidance
- DailyMed - Pfizer ZITHROMAX prescribing informationDrug company labelTertiaryPage dated 2026-07-29
- Muanda et al. - Use of antibiotics during pregnancy and risk of spontaneous abortionUS governmentPrimaryIndependent check
- Hegger et al. - Exposure to macrolides during pregnancy and spontaneous abortionsUS governmentPrimaryIndependent check
- Hume-Nixon et al. - Azithromycin perinatal outcomes reviewUS governmentPrimaryIndependent check
- Fan et al. - Macrolide prescribing during pregnancy and child outcomesUS governmentPrimaryIndependent check
- Andersson et al. - Macrolides and major birth defectsUS governmentPrimaryIndependent check
- Tran et al. - First-trimester macrolides and congenital malformationsUS governmentPrimaryIndependent check
- Otoo et al. - Prenatal azithromycin exposure and neurodevelopmental disordersUS governmentPrimaryIndependent check
- Sutton et al. - Perinatal pharmacokinetics of azithromycin for cesarean prophylaxisUS governmentPrimaryIndependent check
- Salman et al. - Azithromycin transfer into breast milk of African mothersUS governmentPrimaryIndependent check
- Almaramhy and Al-Zalabani - Macrolide exposure and pyloric stenosis meta-analysisUS governmentPrimaryIndependent check
Last reviewed 2026-10-16
Independent check 2026-10-16
Not yet clinician-reviewed
Ask your provider about your situation.