Can You Use Amoxicillin in the First Trimester of Pregnancy?
Yes, amoxicillin can be safely used during the first trimester of pregnancy for bacterial infections, as it is classified as FDA Pregnancy Category B and multiple guidelines explicitly recommend it as safe throughout all trimesters. 1, 2
Guideline-Based Safety Profile
Amoxicillin is explicitly listed as safe for use during all trimesters of pregnancy by the European Society of Cardiology (ESC), which classifies it as FDA Group B. 1 The ESC guidelines specifically state that "antibiotics that can be given during all trimesters of pregnancy are penicillin, ampicillin, amoxicillin, erythromycin, mezlocillin, and cephalosporins" when treating serious infections like infective endocarditis. 1
The ERS/TSANZ Task Force on Airways Diseases similarly classifies amoxicillin as "compatible" for use during the first trimester (T1), second trimester (T2), third trimester (T3), labor, and breastfeeding. 1
FDA Drug Label Information
The FDA label for amoxicillin states that "reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg with no evidence of harm to the fetus due to amoxicillin." 2 However, the label appropriately notes that "there are no adequate and well-controlled studies in pregnant women" and recommends use "only if clearly needed." 2 This conservative language is standard FDA terminology for Category B drugs and does not contraindicate first-trimester use when treating bacterial infections.
Research Evidence on Safety
Overall Safety Data
A large population-based Danish study of 401 pregnant women who received amoxicillin during pregnancy found no increased risk of adverse outcomes. 3 The adjusted odds ratios showed: low birth weight 0.63 (95% CI 0.26-1.53), preterm delivery 0.77 (95% CI 0.49-1.21), congenital malformation 1.16 (95% CI 0.54-2.50), and spontaneous abortion 0.89 (95% CI 0.66-1.18). 3 Notably, children born to amoxicillin-exposed mothers had a mean birth weight 57g higher than controls. 3
Oral Cleft Controversy
One case-control study from 2012 suggested a potential association between amoxicillin use and oral clefts, but this finding requires careful interpretation. 4 The study found an adjusted OR of 2.0 (95% CI 1.0-4.1) for cleft lip with/without cleft palate, with higher risk for third-month exposure (OR 4.3,95% CI 1.4-13.0). 4 However, a 2023 systematic review examining this issue concluded that "no major congenital anomaly was reported for the administration of amoxicillin" and noted the cleft palate risk was very low. 5 The ERS/TSANZ guidelines acknowledge this concern but note the "risk is very low." 1
Amoxicillin-Clavulanic Acid Considerations
The combination of amoxicillin with clavulanic acid requires additional consideration. 1 The ERS/TSANZ guidelines note that "amoxicillin+clavulanic acid is not recommended in women at risk of pre-term delivery" due to a very low risk of necrotizing enterocolitis in the fetus. 1 However, a 2022 review concluded that "results available to date do not support an increased risk of necrotizing enterocolitis with the use of amoxicillin-clavulanic acid in late pregnancy" and stated it "can be prescribed at any stage of pregnancy, including just before delivery." 6
Clinical Algorithm for First Trimester Use
When treating bacterial infections in the first trimester:
Amoxicillin alone is preferred over amoxicillin-clavulanic acid to avoid any theoretical concerns about necrotizing enterocolitis, though evidence does not strongly support this risk. 1, 6
Use standard therapeutic doses as recommended for non-pregnant patients, as amoxicillin pharmacokinetics are not significantly altered in early pregnancy. 2
Document the indication clearly to ensure the benefit of treating the bacterial infection outweighs any theoretical risks. 2
Counsel patients about the very low potential risk of oral clefts (if this concerns them), but emphasize that untreated bacterial infections pose greater risks to both mother and fetus. 5, 4
Common Pitfalls to Avoid
Do not withhold amoxicillin in the first trimester when treating serious bacterial infections such as urinary tract infections, respiratory infections, or endocarditis, as untreated infections pose far greater risks than the medication. 1
Do not confuse amoxicillin safety with azole antifungals, which are strictly contraindicated in the first trimester due to documented teratogenicity. 7, 8 Amoxicillin has an entirely different safety profile.
Do not assume all antibiotics are equally safe - aminoglycosides, quinolones, and tetracyclines carry definite fetal risks and should be avoided. 1