Cephalexin Safety in First Trimester of Pregnancy
Cephalexin is safe to use during the first trimester of pregnancy, with moderate-quality evidence showing no increased risk of congenital malformations or adverse fetal outcomes. 1, 2
Evidence for First-Trimester Safety
Multiple high-quality guidelines explicitly recommend cephalexin as a preferred systemic antibiotic for pregnant patients, including during the first trimester. The 2025 North American guidelines for hidradenitis suppurativa management state that oral cephalexin should be used in pregnant patients requiring systemic antibiotics, with moderate-quality evidence supporting its safety 1. The American College of Obstetricians and Gynecologists and European Respiratory Society both classify cephalexin as compatible throughout all trimesters, with decades of clinical experience demonstrating no teratogenic effects 2.
Large population-based studies confirm the absence of teratogenic risk. A Hungarian case-control surveillance study of 22,865 pregnant women with congenital abnormalities found no detectable teratogenic potential when cephalexin was used during the critical second-to-third month period of organogenesis 3. A prospective Israeli cohort study of 106 first-trimester exposures to cefuroxime (another cephalosporin) showed major malformation rates of 3.2% in exposed women versus 2% in controls—a statistically non-significant difference 4.
Adult Dosing Regimen
The standard adult dose of cephalexin is 250 mg every 6 hours, with 500 mg every 12 hours acceptable for uncomplicated infections such as cystitis or skin infections. 5
- For more severe infections or less susceptible organisms, doses up to 4 grams daily in divided doses may be required 5
- Cystitis should be treated for 7-14 days 5
- If doses exceeding 4 grams daily are needed, parenteral cephalosporins should be considered instead 5
Clinical Context and Positioning
Cephalexin ranks among the safest first-line antibiotics for pregnancy alongside amoxicillin. Both penicillins and cephalosporins are classified as the preferred antibiotic classes for pregnant women, with cephalexin and amoxicillin specifically highlighted as first-line agents 2. This recommendation is based on extensive safety data across multiple cohorts and compatibility throughout pregnancy and breastfeeding 2.
For pregnant patients with hidradenitis suppurativa requiring systemic antibiotics, cephalexin is suggested alongside azithromycin and clindamycin, all with moderate-quality evidence. 1 For recurrent UTI prophylaxis during pregnancy, postcoital cephalexin 250 mg has proven highly effective, reducing UTI incidence from 130 infections pre-prophylaxis to only 1 infection during pregnancy in a clinical study 6.
Important Caveats and Limitations
Cephalexin should not be used as monotherapy for acute pyelonephritis in pregnancy. Oral cephalosporins achieve lower blood concentrations than parenteral agents, making them inadequate for severe upper urinary tract infections 7. A prospective study showed that while oral cephalexin was effective for non-bacteremic pyelonephritis (91.4% success rate), bacteremia occurred in 14.4% of cases and mandated IV therapy 8.
Penicillin allergy requires careful assessment before prescribing cephalexin. High-risk penicillin allergy—defined as history of anaphylaxis, angioedema, respiratory distress, or urticaria—contraindicates cephalosporin use 2. In these patients, alternatives such as clindamycin or vancomycin should be used instead 2. For non-severe penicillin allergies, cephalexin remains an acceptable option 2.
Monitor for drug interactions, particularly with metformin. Cephalexin increases metformin plasma concentrations by 34% (Cmax) and 24% (AUC) while decreasing renal clearance by 14%, necessitating careful monitoring and potential dose adjustment of metformin in co-administered patients 5.
Antibiotics to Avoid in Pregnancy
Several antibiotics are contraindicated during pregnancy and should never be substituted for cephalexin:
- Doxycycline and tetracyclines: Cause fetal tooth discoloration, transient bone growth suppression, and potential maternal fatty liver; strongly contraindicated 1, 2
- Fluoroquinolones (ciprofloxacin, levofloxacin): Animal studies show cartilage toxicity; should be avoided 2
- Trimethoprim-sulfamethoxazole: Increases risk of preterm birth, low birthweight, kernicterus, and fetal hemolytic anemia, especially in first trimester 1, 2
- Metronidazole: May increase risk of low birthweight and neuroblastoma 1
- Erythromycin: Associated with elevated liver enzymes and adverse outcomes 1