Is levofloxacin (fluoroquinolone) safe to use during pregnancy?

Levofloxacin in Pregnancy: Safety Considerations

Levofloxacin should be avoided during pregnancy due to potential risks to the fetus, and alternative antibiotics should be used whenever possible. 1, 2, 3

Safety Classification and Risks

• FDA Pregnancy Category C: Animal studies show adverse effects on the fetus, and there are no adequate well-controlled studies in pregnant women 3
• Fluoroquinolones, including levofloxacin, are generally contraindicated during pregnancy according to multiple guidelines 1, 2
• The CDC and European guidelines specifically recommend avoiding fluoroquinolones during pregnancy 2

Evidence from Animal Studies

• Levofloxacin was not teratogenic in rats at doses up to 9.4 times the highest recommended human dose 3
• However, high oral doses in rats (810 mg/kg/day) caused decreased fetal body weight and increased fetal mortality 3
• No teratogenicity was observed in rabbits at doses up to 1.1 times the highest recommended human dose 3

Human Data and Recent Research

• Recent systematic reviews and meta-analyses (2018) suggest that quinolone exposure during first trimester was not associated with increased risk of:

  • Birth defects (OR = 0.89,95% CI 0.72-1.09)
  • Stillbirth (OR = 1.32,95% CI 0.33-5.34)
  • Preterm birth (OR = 1.10,95% CI 0.83-1.48)
  • Low birth weight (OR = 1.29,95% CI 0.54-3.12) 4

• A 2014 observational cohort study found no increased risk of major birth defects (2.4%; adjusted OR 0.91) or spontaneous abortion after fluoroquinolone exposure in the first trimester 5

  • However, a non-significant increase in major birth defects was noted after moxifloxacin exposure (6.5%; crude OR 2.40) 5

Clinical Recommendations

Alternative Antibiotics During Pregnancy

When treating infections during pregnancy, consider these safer alternatives:

• First-line options: Ampicillin, cefotaxime, ceftriaxone, or TMP-SMZ 1
• For Salmonella infections specifically: Ampicillin, cefotaxime, ceftriaxone, or TMP-SMZ are recommended instead of fluoroquinolones 1

Special Circumstances

• If levofloxacin is absolutely necessary (e.g., life-threatening infection with resistant organisms):
  • Use only when potential benefit justifies the potential risk to the fetus 3
  • Consider detailed fetal ultrasound examination 5
  • Monitor closely for adverse effects

Breastfeeding Considerations

• Levofloxacin is excreted in human milk 3
• A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother 3
• Most sources recommend avoiding fluoroquinolones during breastfeeding if possible, due to potential risks of arthropathy and cartilage damage in the infant 2, 6

Key Warnings and Precautions

• Fluoroquinolones can cause arthropathy and osteochondrosis in juvenile animals 3
• Risk of QT prolongation, tendinopathy, CNS toxicity, and other adverse effects 2
• Potential for drug interactions with other medications 2

Conclusion

While recent human data suggests the risk of birth defects may be lower than previously thought, the precautionary principle and multiple guidelines still recommend avoiding levofloxacin during pregnancy whenever possible. Alternative antibiotics with established safety profiles should be used as first-line agents for treating infections in pregnant women.