Is amoxicillin (amoxicillin) safe to use during pregnancy, particularly in a patient with a history of allergies or sensitivities to penicillin (penicillin) or other antibiotics?

Is Amoxicillin Safe During Pregnancy?

Yes, amoxicillin is safe to use during pregnancy and is considered a first-line antibiotic for treating infections in pregnant women. 1, 2

Evidence from FDA Drug Labeling

The FDA label for amoxicillin explicitly addresses pregnancy safety:

• Reproduction studies in mice and rats at doses up to 2000 mg/kg (3-6 times the human dose) showed no evidence of harm to the fetus 1
• While adequate well-controlled studies in pregnant women are lacking, amoxicillin should be used during pregnancy when clearly needed 1
• The FDA classification supports its use when the clinical situation warrants antibiotic therapy 1

Clinical Guidelines Supporting Penicillin Use in Pregnancy

Penicillins, including amoxicillin, are universally recommended as first-line antibiotics during pregnancy across multiple clinical scenarios:

• For Group B Streptococcus infections, penicillin and ampicillin (closely related to amoxicillin) are the preferred agents with 100% GBS susceptibility worldwide 3, 4
• For syphilis treatment in pregnancy, penicillin is the only proven effective and safe treatment for both maternal infection and prevention of fetal infection 5
• Penicillins are recommended as first-line therapy for most bacterial infections during pregnancy, with cephalosporins as alternatives 2

Special Consideration: Penicillin Allergy History

If your patient reports a penicillin allergy, this requires careful evaluation rather than automatic avoidance:

• Most individuals who report penicillin allergy are not truly allergic and are not at risk for hypersensitivity reactions 6
• Unverified penicillin allergy in pregnancy is associated with increased cesarean section rates (10% higher), longer hospital stays, exposure to broader-spectrum antibiotics, and higher rates of adverse drug reactions 7
• For pregnant women with reported penicillin allergy requiring penicillin therapy (such as for syphilis), desensitization is recommended rather than using alternative agents 5, 8

Algorithm for Managing Reported Penicillin Allergy:

1. Take a detailed allergy history to determine if the reaction was truly IgE-mediated (anaphylaxis, angioedema, urticaria, respiratory distress) or a non-allergic reaction (rash, GI upset) 9, 6

2. For non-severe reactions (mild rash, GI symptoms): Consider using amoxicillin or a first-generation cephalosporin like cefazolin, as cross-reactivity is approximately 10% and these are often tolerated 5, 9

3. For severe/high-risk allergy history (anaphylaxis, angioedema):

   • Refer for penicillin skin testing, which is safe during pregnancy 6, 8, 10
   • If skin testing is negative, proceed with oral amoxicillin challenge in a monitored setting 10
   • If truly allergic and penicillin is essential (e.g., syphilis), perform desensitization using oral penicillin V with increasing doses over 4-6 hours, then administer full-dose parenteral therapy 8

4. Desensitization is safe in pregnancy: A study of 15 pregnant women with confirmed penicillin allergy (positive skin tests) showed successful oral desensitization with only minor reactions (pruritus or urticaria in 33%), no interruption of therapy needed, and all infections cured 8

Contraindicated Antibiotics During Pregnancy

To provide context, these antibiotics should be avoided:

• Tetracyclines: Contraindicated after 5 weeks of pregnancy due to hepatotoxicity and staining of fetal bones and teeth 5, 2
• Aminoglycosides: Should not be prescribed due to nephrotoxicity and ototoxicity; reserved only for life-threatening infections 2
• Fluoroquinolones (gyrase inhibitors): Contraindicated as a precautionary measure 2
• Erythromycin: Does not reliably cure fetal infection in syphilis cases 5

Clinical Bottom Line

Amoxicillin is one of the safest antibiotics available for use during pregnancy and should not be withheld when clinically indicated. The extensive safety data, lack of teratogenic effects in animal studies, and decades of clinical experience support its use throughout all trimesters of pregnancy. 1, 2

The greater risk lies in undertreating maternal infections or using suboptimal alternative antibiotics based on unverified penicillin allergy reports. 6, 7 When penicillin allergy is reported, pursue verification through detailed history-taking and consider allergy testing or desensitization rather than defaulting to broader-spectrum or less effective alternatives. 6, 8, 10