Is clarithromycin (macrolide antibiotic) safe to use during the first trimester of pregnancy?

Clarithromycin Use in First Trimester of Pregnancy

Clarithromycin should be avoided during the first trimester of pregnancy due to demonstrated teratogenic effects in animal studies and increased risk of spontaneous abortion in humans. 1, 2

Safety Concerns

Animal Studies and Human Data

• Clarithromycin has been demonstrated to be a teratogen in animal studies 2
• In pregnant mice and rats, clarithromycin caused:
  • Cardiovascular anomalies
  • Cleft palate
  • Increased post-implantation loss 1
• Human studies have shown:
  • Significantly increased risk of spontaneous abortion (14% vs 7% in control group) 3, 4
  • A Danish nationwide cohort study found a 56% increased hazard of miscarriage after exposure to clarithromycin in early pregnancy (HR 1.56,95% CI 1.14-2.13) 4

FDA Labeling

The FDA label explicitly states that clarithromycin is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If pregnancy occurs while taking clarithromycin, the patient should be apprised of the potential hazard to the fetus. 1

Alternative Options

Preferred Macrolide in Pregnancy

• Azithromycin is the recommended macrolide antibiotic when a macrolide is indicated during pregnancy (BIII) 2
• Azithromycin did not produce birth defects in animal studies 2
• Although human experience with azithromycin in first trimester is limited, it has a better safety profile than clarithromycin 2, 5

Other Antibiotic Options

• Beta-lactam antibiotics (penicillins, cephalosporins) have not been associated with teratogenicity or increased toxicity in pregnancy 2
• For serious respiratory infections when indicated, quinolones can be used (CIII) 2
• Avoid tetracyclines during pregnancy due to increased hepatotoxicity and staining of fetal teeth and bones 2

Clinical Decision Algorithm

1. First question: Is there an alternative antibiotic that can effectively treat the infection?

   • If YES: Use penicillins or cephalosporins as first-line agents
   • If NO: Proceed to step 2

2. If a macrolide is specifically required:

   • Use azithromycin instead of clarithromycin (BIII) 2
   • Azithromycin has better placental safety profile and is the drug of choice among macrolides during pregnancy 2

3. If clarithromycin is the only option (rare situation):

   • Carefully weigh benefits vs. risks
   • Consider that clarithromycin has been shown to have enhanced placental passage compared to other macrolides 6
   • Document the clinical necessity and informed consent discussion

Important Considerations

• The risk of spontaneous abortion with clarithromycin appears to be significantly higher than with other antibiotics like penicillin or erythromycin 4
• While two studies with at least 100 women with first-trimester exposure to clarithromycin did not document a clear increase in or specific pattern of birth defects, the increased risk for spontaneous abortion remains concerning 2
• The FDA categorizes clarithromycin as not recommended during pregnancy based on animal reproduction studies showing adverse effects on the fetus 1

Remember that decades of clinical experience with penicillins, cephalosporins, and erythromycins have documented their overall safety for the fetus, making these classes of drugs most favored for use in pregnancy for susceptible infections. 7