Are antihistamines (anti-allergic medications) safe to use during pregnancy?

Are Antihistamines Safe During Pregnancy?

Yes, antihistamines are safe to use during pregnancy, with cetirizine and loratadine being the preferred first-line options across all trimesters, including the first trimester when organogenesis occurs. 1

Recommended First-Line Antihistamines

The safest antihistamines during pregnancy are cetirizine and loratadine, both classified as FDA Pregnancy Category B with extensive human safety data demonstrating no increased risk of congenital malformations. 1

• Cetirizine has the most robust safety evidence and is particularly recommended, with no documented increase in birth defects even with first trimester exposure 1
• Loratadine carries equally strong safety data with extensive human observational studies confirming safety across all trimesters 1
• Both medications offer the advantage of minimal sedation compared to older antihistamines, improving maternal quality of life without compromising safety 2, 1
• A large meta-analysis of H1 antihistamines found no increased risk of major malformations (OR 1.07; 95% CI 0.98-1.16), spontaneous abortion, prematurity, or low birth weight 3

Alternative Safe Options

Chlorpheniramine (a first-generation antihistamine) is also safe throughout pregnancy with a long-established safety record, though it causes more sedation. 2

• Chlorpheniramine has been specifically recommended by the American Academy of Allergy, Asthma, and Immunology as a first-choice agent with sufficient human data showing no significant increase in congenital malformations during first trimester use 2
• The main drawback is sedative effects that may impair maternal performance, making second-generation antihistamines preferable from a quality of life perspective 2
• UK clinicians often choose chlorpheniramine when antihistamine therapy is necessary because of its long safety record 2

Critical Medications to Avoid

Hydroxyzine is the only antihistamine specifically contraindicated during early pregnancy based on animal teratogenicity data. 2, 1

• Use cetirizine (the active metabolite of hydroxyzine) instead, which has an excellent safety profile 2
• Levocetirizine, desloratadine, azelastine, and fexofenadine should be avoided due to limited human pregnancy data when better-studied alternatives exist 1, 4

Dangerous Combinations to Avoid

Never combine antihistamines with oral decongestants (phenylephrine, pseudoephedrine) during the first trimester. 2, 1

• Oral decongestants have conflicting reports of association with gastroschisis and small intestinal atresia 2, 1
• The risk of malformations increases further when decongestants are combined with acetaminophen or salicylates 2, 1
• If decongestants are absolutely necessary, reserve them for after the first trimester and use for the shortest duration possible 1

Optimal Treatment Algorithm

For pregnant women with allergic symptoms, follow this hierarchy:

1. Start with intranasal corticosteroids (budesonide preferred) as first-line therapy - these are actually safer and more effective than antihistamines with minimal systemic absorption 1

2. Add cetirizine or loratadine if additional symptom control is needed 1

3. Consider sodium cromolyn nasal spray if patient refuses corticosteroids, though it requires four-times-daily dosing which limits compliance 1

4. Use chlorpheniramine if sedation is not a concern or if patient has prior favorable response 2

Dosing Considerations

Use the lowest effective dose for the shortest possible time to minimize fetal exposure. 2

• Standard chlorpheniramine dosing is 4-12 mg 2
• Cetirizine dose should be halved in moderate renal impairment and avoided in severe renal impairment (creatinine clearance < 10 mL/min) 2
• Loratadine should be used with caution in severe renal impairment 2

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 between agents 1, 4

Do not reflexively choose first-generation antihistamines based solely on "longer history of use" - second-generation agents (cetirizine, loratadine) now have comparable safety data without sedation risks 1

Do not overlook intranasal corticosteroids, which are often more effective than antihistamines for rhinitis and have excellent safety profiles 1

Do not use combination products containing decongestants during the first trimester, as this significantly increases malformation risk 2, 1