What are the safe antihistamines (anti histamines) for use during pregnancy?

Safe Antihistamines in Pregnancy

Second-generation antihistamines cetirizine and loratadine are the preferred first-line antihistamines during pregnancy, with the most extensive safety data demonstrating no increased risk of congenital malformations across all trimesters. 1, 2, 3

Recommended Antihistamine Options by Safety Profile

First-Line Choices (Best Safety Data)

• Cetirizine has the most robust safety evidence and is particularly recommended for third trimester use, with FDA Pregnancy Category B classification 1, 2, 3
• Loratadine also carries FDA Pregnancy Category B status with extensive human observational data confirming safety across all trimesters 1, 3
• Both agents have accumulated safety data comparable to first-generation antihistamines but without the sedative effects that impair maternal performance 1

Second-Line Options (Acceptable with Caveats)

• Chlorphenamine (chlorpheniramine) is frequently chosen by UK clinicians due to its long safety record spanning decades, though sedation is a significant drawback 1
• Diphenhydramine is commonly used and has overall good safety data, but historical case-control studies suggested a possible association with cleft palate that requires caution, particularly in first trimester 1

Antihistamines to Avoid

• Hydroxyzine is specifically contraindicated during early pregnancy based on animal teratogenicity data 1
• Levocetirizine, desloratadine, azelastine, and fexofenadine have limited human pregnancy data and should be avoided when better-studied alternatives exist 1, 4

Critical Timing Considerations

• The first trimester (organogenesis period) is the most critical window for potential medication-related congenital malformations 1, 4
• While caution is advised throughout pregnancy, the accumulated evidence shows second-generation antihistamines (cetirizine, loratadine) have excellent safety records even with first trimester exposure 1
• A meta-analysis of over 200,000 first-trimester antihistamine exposures failed to demonstrate increased teratogenic risk 5, 6

Alternative and Adjunctive Therapies

Intranasal Corticosteroids (Often Superior to Antihistamines)

• Intranasal corticosteroids are actually the safest and most effective first-line treatment for rhinitis during pregnancy, with minimal systemic absorption 2, 6
• Budesonide (Pregnancy Category B) is the preferred intranasal corticosteroid if initiating therapy during pregnancy 1, 2, 3
• Fluticasone and mometasone also have favorable safety profiles 2

Other Safe Options

• Sodium cromolyn nasal spray (Pregnancy Category B) is safe but requires frequent four-times-daily dosing, limiting patient acceptance 1, 7
• Montelukast has reassuring animal data and Pregnancy Category B classification, but should be reserved for patients with uniquely favorable pre-pregnancy responses 1, 2, 7

Medications to Avoid

• Oral decongestants (phenylephrine, pseudoephedrine) should be avoided during first trimester due to conflicting reports associating them with gastroschisis and small intestinal atresia 1, 2
• Risk increases when decongestants are combined with acetaminophen or salicylates 1, 7
• Intranasal antihistamines should be avoided during pregnancy 3

Practical Treatment Algorithm

For any trimester:

1. Start with intranasal corticosteroids (budesonide preferred) as first-line therapy for rhinitis symptoms 2, 6
2. Add cetirizine or loratadine if additional symptom control needed 2, 3
3. Consider sodium cromolyn if patient refuses corticosteroids, though efficacy is lower 1, 7
4. Reserve montelukast only for patients with documented excellent pre-pregnancy response 1, 7

For first trimester specifically:

• Avoid oral decongestants entirely 1, 2
• Avoid newer antihistamines with limited human data (levocetirizine, desloratadine, fexofenadine) 4, 7
• Never use hydroxyzine 1

Common Pitfalls to Avoid

• Do not assume all antihistamines have equivalent safety profiles—they do not, and the quality of human pregnancy data varies dramatically 2, 4
• 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 1
• Do not overlook intranasal corticosteroids, which are often more effective than antihistamines and have excellent safety profiles 2, 6
• Do not combine oral decongestants with acetaminophen or NSAIDs during pregnancy, as this increases malformation risk 1, 7