Is it safe to use Bisolvon (bromhexine) and cetirizine during pregnancy?

Safety of Bisolvon (Bromhexine) and Cetirizine in Pregnancy

Cetirizine is safe to use during pregnancy and should be preferred as a first-line antihistamine, while bromhexine (Bisolvon) should be avoided due to concerning animal data showing interference with implantation and conception.

Cetirizine: Recommended and Safe

Cetirizine is one of the preferred antihistamines during pregnancy based on extensive clinical experience and guideline recommendations 1. The 2020 ERS/TSANZ Task Force specifically states that loratadine or cetirizine should be preferred as they have been most extensively studied 1. While guidelines note that first-generation antihistamines should be avoided due to sedative and anticholinergic properties, second-generation antihistamines like cetirizine are considered "probably safe" 2.

Supporting Evidence for Cetirizine Safety:

• Large-scale safety data: A 2026 systematic review analyzing over 186,000 exposures from Scandinavian registries found no statistically significant associations between second-generation antihistamines and major congenital malformations, spontaneous abortions, or premature births 3

• Prospective cohort studies: Multiple studies demonstrate reassuring outcomes:

  • UCB Pharma database (228 pregnancies): 83.7% resulted in live births with only 2 congenital malformations reported 4
  • Berlin teratology center study (196 first-trimester exposures): No increased risk of major birth defects (OR 1.07; CI 0.21-3.59) 5
  • Meta-analysis: Cetirizine not associated with increased teratogenic risk 6

• Breastfeeding compatibility: The relative infant dose remains below the 5% safety threshold, making it compatible with breastfeeding 3

Important Caveats:

• Although H1-antihistamines have been generally safe, some studies reported associations between specific antihistamines and certain birth defects 1
• One older study suggested antihistamine use in the last 2 weeks of pregnancy was associated with retrolental fibroplasia in premature infants, though this has not been corroborated 1
• Antihistamines may theoretically reduce milk production during breastfeeding 1

Bromhexine (Bisolvon): Not Recommended

Bromhexine should be avoided during pregnancy due to concerning preclinical data and lack of human safety evidence.

Critical Safety Concerns:

• Animal reproduction toxicity: A 2006 rat study demonstrated that bromhexine acts as an antiimplantation agent, causing:

  • 50-80% inhibition in glycosidic moiety incorporation
  • Distinct reduction in implantation sites
  • Interference with conception (16/46 pregnancies affected)
  • Reduction in fetal sizes and dwarfing of fetuses 7

• Mechanism of harm: Bromhexine interferes with focal adhesive molecules of the uterus and trophectoderm, affecting blastocyst attachment and conception 7

• Lack of human pregnancy data: No guideline evidence or human studies address bromhexine safety in pregnancy. The available research focuses on COVID-19 treatment efficacy, not pregnancy safety 8, 9

Clinical Algorithm:

For allergic symptoms during pregnancy:

1. First-line: Use cetirizine 10 mg daily (or loratadine as alternative)
2. Avoid: Bromhexine/Bisolvon entirely
3. Avoid: First-generation antihistamines due to sedative effects
4. Avoid: Oral decongestants (risk of fetal gastroschisis and maternal hypertension) 2

For cough/mucus symptoms:

• Consider saline nasal rinses and topical corticosteroid nasal sprays as safer alternatives 2
• Avoid mucolytics like bromhexine due to lack of safety data and concerning animal studies

Timing considerations:

• Cetirizine exposure primarily studied in first trimester when organogenesis occurs - reassuring data 4, 5
• Most antihistamine exposure data comes from first-trimester use, which is the most critical period