Is Rifaximin (antibiotic) safe to use during pregnancy?

Rifaximin Use in Pregnancy

Primary Recommendation

Rifaximin should be avoided during pregnancy due to demonstrated teratogenic effects in animal studies, though it may be considered when benefits clearly outweigh risks in situations where safer alternatives are contraindicated or ineffective. 1

Evidence Base

FDA Drug Label Information

The FDA label for rifaximin (XIFAXAN) provides critical safety data:

• Teratogenic effects were observed in animal reproduction studies at doses approximately 0.9 to 5 times the recommended human doses in rats and 0.7 to 33 times in rabbits 1
• Specific malformations documented in animal studies include:
  • Ocular abnormalities (both rats and rabbits) 1
  • Cleft palate 1
  • Jaw abnormalities (agnathia, jaw shortening, brachygnathia) 1
  • Cardiac malformations 1
  • Lumbar spine defects 1
  • Incomplete ossification 1
• No human pregnancy data are available to inform drug-associated risks 1
• The estimated background risk of major birth defects in the U.S. general population is 2-4% 1

Clinical Context and Theoretical Advantages

Despite the concerning animal data, rifaximin has theoretical advantages in pregnancy due to its pharmacokinetic profile:

• Minimal systemic absorption (<0.4%) results in extremely low maternal blood levels 2
• High fecal concentrations (>8000 mcg/g) with minimal systemic exposure 2
• One expert opinion suggested rifaximin "should be useful in treating hosts such as pregnant women in whom the currently favored fluoroquinolones are contraindicated" based on its lack of systemic absorption 3

However, this theoretical advantage is contradicted by the FDA's animal teratogenicity data, which must take precedence in clinical decision-making. 1

Clinical Decision Algorithm

When Rifaximin Might Be Considered:

1. Severe infectious diarrhea where:

   • Safer alternatives (azithromycin, amoxicillin) have failed or are contraindicated 4
   • The maternal condition poses significant risk to pregnancy continuation 1
   • Benefits clearly outweigh the documented teratogenic risk 1

2. Hepatic encephalopathy in pregnant women with cirrhosis where:

   • No safer alternative exists
   • Maternal mortality risk is substantial without treatment 1

Preferred Alternatives During Pregnancy:

For infectious diarrhea and other indications where rifaximin might be considered:

• Azithromycin is the preferred macrolide with reassuring safety data and CDC recommendation as drug of choice during pregnancy 5
• Amoxicillin is widely used with extensive safety experience 6
• Nitrofurantoin (after first trimester) for urinary infections 6

Important Caveats

Risk Communication:

• Advise pregnant women of the potential risk to the fetus if rifaximin use is being considered 1
• The lack of human data means we cannot quantify the actual risk, only that animal studies showed harm at clinically relevant doses 1
• Animal teratogenicity at doses close to human therapeutic doses (0.7-5 times) is particularly concerning 1

Timing Considerations:

• First trimester exposure carries the highest theoretical risk for structural malformations based on the types of defects seen in animal studies (cardiac, craniofacial, skeletal) 1
• If inadvertent exposure occurs, individual risk assessment and detailed fetal anatomic ultrasound should be considered 1

Lactation:

• No information exists regarding rifaximin presence in human milk 1
• Given minimal systemic absorption, theoretical risk to breastfed infant may be low, but this remains unproven 1

Comparison with Related Rifamycins

The limited pregnancy experience with other rifamycin antibiotics provides context:

• Rifampin has more extensive anecdotal use in pregnancy without documented adverse outcomes, though data remain limited 4
• Rifabutin has insufficient data for recommendation during pregnancy and should be used with caution 4
• Rifaximin's minimal absorption does not eliminate teratogenic risk, as the animal data demonstrate 1