What antihistamine (antihistaminic) is safe to use during pregnancy?

Safe Antihistamines in Pregnancy

Cetirizine and loratadine are the safest antihistamines to use during pregnancy, including the first trimester, with the most extensive human safety data showing no increased risk of congenital malformations. 1

First-Line Antihistamine Recommendations

The preferred antihistamines during pregnancy are:

• Cetirizine - FDA Pregnancy Category B with the most robust safety evidence across all trimesters, including data from 228 pregnancies showing 83.7% live births with only 2 congenital malformations (consistent with background rates) 2
• Loratadine - FDA Pregnancy Category B with safety data from 2,147 first-trimester exposures demonstrating no increased teratogenic risk 1, 3

Both agents have accumulated sufficient human observational data through large birth registries, case-control studies, and cohort studies to confirm their safety profile comparable to first-generation antihistamines, but without sedative effects that impair maternal performance 4, 1

Alternative First-Generation Option

• Chlorphenamine (chlorpheniramine) - Often chosen by UK clinicians when antihistamine therapy is necessary due to its long safety record, with meta-analysis of 200,000 first-trimester exposures showing no increased teratogenic risk 4, 3, 5

However, chlorphenamine's sedating properties and possible effects on performance make it less desirable than cetirizine or loratadine 4

Critical Timing Considerations

The first trimester (organogenesis period) is the most critical window for medication-related congenital malformations 4, 6. Despite this concern, the accumulated evidence demonstrates that cetirizine and loratadine maintain excellent safety records even with first-trimester exposure 1

Antihistamines to Specifically Avoid

• Hydroxyzine - Specifically contraindicated during early pregnancy based on animal teratogenicity data and UK manufacturer's Summary of Product Characteristics 4, 1
• Levocetirizine - Should be avoided during first trimester due to limited safety data 6, 1
• Desloratadine, azelastine, fexofenadine - Have insufficient human pregnancy data and should be avoided when better-studied alternatives exist 1
• Diphenhydramine - Use with caution due to case-control study suggesting association with cleft palate 4

Superior Alternative: Intranasal Corticosteroids

Intranasal corticosteroids are actually more effective than antihistamines for rhinitis and have excellent safety profiles with minimal systemic absorption 1, 3:

• Budesonide (Pregnancy Category B) is the preferred intranasal corticosteroid if initiating therapy during pregnancy 1, 7
• Beclometasone is also considered low-risk 3

Additional Safe Options

• Sodium cromolyn nasal spray - Pregnancy Category B, safe but requires four-times-daily dosing which limits patient acceptance 4, 1, 3
• Montelukast - Pregnancy Category B with reassuring animal data, but reserve for patients with documented excellent pre-pregnancy response 4, 1

Medications to Avoid

Oral decongestants (pseudoephedrine, phenylephrine) must be avoided during the first trimester due to conflicting reports associating them with gastroschisis and small intestinal atresia 4, 6. The risk increases when combining decongestants with acetaminophen or salicylates 4, 1

Practical Treatment Algorithm

1. Start with intranasal budesonide as first-line therapy for rhinitis symptoms 1
2. Add cetirizine or loratadine if additional symptom control is needed 1
3. Consider sodium cromolyn if patient refuses corticosteroids, though efficacy is lower 1
4. Use chlorphenamine only if second-generation antihistamines are unavailable 4

Common Pitfalls to Avoid

• Do not assume all antihistamines have equivalent safety profiles - the quality of human pregnancy data varies dramatically between agents 6, 1
• Do not reflexively choose first-generation antihistamines based solely on "longer history of use" - second-generation agents now have comparable safety data without sedation risks 4, 1
• Do not overlook intranasal corticosteroids, which are often more effective than antihistamines with excellent safety profiles 1
• Do not combine oral decongestants with acetaminophen or NSAIDs during pregnancy, as this increases malformation risk 4, 1