Is nintedanib (generic name) safe to use during pregnancy?

Nintedanib Use During Pregnancy

Nintedanib should not be used during pregnancy due to its mechanism as a tyrosine kinase inhibitor targeting angiogenic pathways (VEGF, PDGF, FGF), which poses substantial teratogenic risk based on its drug class and mechanism of action.

Evidence-Based Contraindication

Drug Class Risk Profile

• Small-molecule tyrosine kinase inhibitors like nintedanib readily cross the placenta due to their molecular characteristics, unlike large IgG-based biologics that have limited first-trimester transfer 1
• Nintedanib competitively binds to VEGF, PDGF, and FGF receptor kinase domains—all critical pathways for fetal vascular and organ development 2

Extrapolation from Related Tyrosine Kinase Inhibitors

• Imatinib (another tyrosine kinase inhibitor) demonstrated teratogenic and embryotoxic effects in animal studies, with human data showing 10% fetal abnormalities and 18% spontaneous abortions among 180 exposed pregnancies 1
• The NCCN guidelines explicitly state that "enough evidence is not available to favor the continuation of" tyrosine kinase inhibitors during pregnancy, emphasizing individual risk-benefit assessment only when maternal survival is at stake 1

Antiangiogenic Agent Precedent

• Targeted agents modulating angiogenesis (bevacizumab, sunitinib, sorafenib) should be avoided in pregnant women based on animal experiments showing fetal malformations and historical experience with thalidomide 1
• Nintedanib's primary mechanism involves VEGF inhibition, placing it squarely in this high-risk category 2

Clinical Decision Algorithm

For Women of Reproductive Age on Nintedanib:

1. Implement effective contraception before initiating nintedanib therapy, given the drug's 10-15 hour terminal half-life and potential for fetal harm 2
2. Discontinue nintedanib immediately upon positive pregnancy test
3. Assess gestational age and timing of exposure to determine fetal risk counseling needs
4. Consider pregnancy termination discussion if exposure occurred during organogenesis (weeks 3-8), similar to recommendations for other high-risk tyrosine kinase inhibitors 1

For Pregnant Women Requiring Pulmonary Fibrosis Treatment:

• Defer nintedanib until after delivery, as no pregnancy-compatible alternatives exist for idiopathic pulmonary fibrosis pharmacotherapy
• Optimize supportive care including oxygen supplementation, pulmonary rehabilitation, and close maternal-fetal monitoring
• The maternal benefit of disease control does not outweigh the substantial teratogenic risk in this non-life-threatening-in-pregnancy condition

Critical Caveats

Lack of Human Pregnancy Data

• Unlike medications with established pregnancy safety profiles (cephalosporins, amoxicillin/clavulanate) that are classified as "Compatible" 3, 4, nintedanib has no human pregnancy safety data
• The ACR guideline notes that small-molecule agents (tofacitinib, baricitinib, apremilast) lack pregnancy evidence, with the panel electing not to make recommendations—but explicitly noting that small molecules are likely to pass through the placenta 1

Contrast with Safer Alternatives in Other Conditions

• For rheumatic diseases, biologics like certolizumab (which lacks Fc chain) can be continued through pregnancy 1
• For respiratory conditions, inhaled bronchodilators and corticosteroids are safe throughout pregnancy 1
• No such safe alternative exists for nintedanib's indication, making pregnancy planning and prevention paramount

Breastfeeding Considerations

• Given nintedanib's small molecular weight and pharmacokinetic profile, excretion in breast milk is highly likely 2
• Breastfeeding should be avoided during nintedanib therapy, extrapolating from recommendations for other small-molecule tyrosine kinase inhibitors