Ceftriaxone Safety in First Trimester Pregnancy
Ceftriaxone is generally considered safe during the first trimester of pregnancy, classified as FDA Pregnancy Category B, with animal studies showing no evidence of embryotoxicity, fetotoxicity, or teratogenicity, though it should be used only when clearly needed as adequate human data remain limited. 1, 2
FDA Classification and Animal Data
- Ceftriaxone is FDA Pregnancy Category B, meaning reproductive studies in mice and rats at doses up to 20 times the usual human dose revealed no evidence of harm to the fetus 1, 2
- Primate studies at approximately 3 times the human dose demonstrated no embryotoxicity or teratogenicity 1, 2
- Rat studies showed no adverse effects on reproductive parameters during gestation and lactation at doses up to 586 mg/kg/day (approximately 20 times the recommended clinical dose) 1, 2
Clinical Guideline Recommendations
- Penicillins and cephalosporins (including ceftriaxone) are considered the safest antibiotic classes during pregnancy and can be used when endoscopic evidence of purulence is present for acute bacterial infections 3
- Beta-lactam antibiotics, including ceftriaxone, have not been associated with teratogenicity or increased toxicity in pregnancy according to CDC guidelines 3
- The 2025 Mayo Clinic guidelines specifically list ceftriaxone plus metronidazole as an alternative peripartum antibiotic regimen with reliable coverage and a favorable adverse effect profile 3
Important Caveats and Limitations
- The FDA label explicitly states "there are no adequate and well-controlled studies in pregnant women" and recommends use "only if clearly needed" 1, 2
- For syphilis treatment specifically, CDC states that data are insufficient to recommend ceftriaxone for maternal infection and prevention of congenital syphilis, with penicillin remaining the only proven effective treatment 4
- One small study (n=11) suggested ceftriaxone may be considered as an alternative for early syphilis in penicillin-allergic pregnant women, but this remains limited evidence 5
Pharmacokinetic Considerations
- Ceftriaxone pharmacokinetics during the third trimester are similar to non-pregnant adults, with no evidence of drug accumulation 6, 7
- The drug crosses the placenta with mean cord blood concentrations of 26 μg/mL (range 9-40 μg/mL) 8
- Standard dosing (2 g/day) appears adequate without adjustment during pregnancy 6, 7
Clinical Experience
- A study of 784 high-risk pregnant women receiving intrapartum ceftriaxone showed reduced neonatal colonization and early-onset infections with excellent safety profile 8
- Japanese perinatal infection studies (n=8) demonstrated 75% efficacy with no adverse reactions in mothers or neonates 9
- Tolerance has been consistently excellent across studies with no premature deliveries attributed to the medication 6, 7
Practical Application
For first trimester use specifically: While ceftriaxone has favorable animal safety data and FDA Category B classification, the lack of controlled human studies in early pregnancy means it should be reserved for situations where the benefit clearly outweighs theoretical risks 1, 2. Penicillins remain the preferred beta-lactam when possible, particularly for syphilis treatment 4.