Is vonoprazan (potassium‑competitive acid blocker) safe for use during pregnancy?

Vonoprazan Safety in Pregnancy

Vonoprazan should generally be avoided during pregnancy due to insufficient human safety data, though animal studies at clinically relevant doses showed no maternal or developmental toxicity. If acid suppression is needed during pregnancy, proton pump inhibitors (PPIs) remain the preferred first-line agents given their extensive safety track record 1.

Key Safety Considerations

Human Data Limitations

• No adequate or well-controlled studies exist in pregnant women 1
• Available pharmacovigilance data from vonoprazan-containing products are insufficient to evaluate risks for major birth defects, miscarriage, or other adverse maternal/fetal outcomes 1
• The FDA labeling explicitly states this data gap

Animal Study Findings

Reassuring findings at therapeutic doses:

• In rats, no adverse embryo-fetal effects occurred at doses up to 27-times the maximum recommended human dose (MRHD) based on AUC comparisons 1
• In rabbits, no embryo-fetal mortality, toxicity, or external/visceral/skeletal abnormalities were observed at doses up to 10-times the MRHD 1
• A 2024 AGA guideline notes that "no maternal or developmental toxicity was observed with vonoprazan exposure in an animal study" 2

Concerning findings at high doses:

• At 130-times the MRHD (300 mg/kg/day in rats), fetal abnormalities included ventricular septal defects, mal-positioned subclavian artery (in 15/19 litters), tail abnormalities, and small anal opening 1
• In pre- and postnatal development studies, pups exposed during lactation showed liver discoloration associated with necrosis, fibrosis, and hemorrhage at 22-times the MRHD, though these effects were likely attributable to lactation exposure rather than in utero exposure 1
• Importantly, these hepatic effects were not observed at doses approximately equal to the MRHD 1

Clinical Decision-Making Algorithm

When acid suppression is needed in pregnancy:

1. First-line: Use PPIs (omeprazole, lansoprazole)

   • Extensive human safety data available
   • No increased risk of congenital malformations, premature births, stillbirths, spontaneous abortions, or low birth weight 3

2. Consider vonoprazan only if:

   • Patient has documented PPI failure for severe acid-related disease
   • The clinical benefit clearly outweighs theoretical risks
   • Patient is counseled about limited human data
   • Report any pregnancy exposure to Phathom Pharmaceuticals at 1-888-775-7428 1

3. Background pregnancy risks to discuss:

   • General population: 2-4% major birth defects, 15-20% miscarriage 1

Important Caveats

• The 2024 AGA guideline on P-CABs recommends not using P-CABs as initial therapy based on cost, access barriers, and fewer long-term safety data compared to PPIs 2
• While animal data at therapeutic doses are reassuring, the absence of human data means we cannot definitively rule out risks that may not manifest in animal models
• The hepatic findings in offspring during lactation studies raise additional concerns about breastfeeding safety (though likely not relevant to pregnancy itself)

Bottom line: The prudent approach is to use well-established PPIs during pregnancy unless there is a compelling clinical reason to use vonoprazan, in which case shared decision-making with thorough counseling about data limitations is essential.