What are the safest antihistamines (anti-allergic medications) for a pregnant woman to use?

Safest Antihistamines for Pregnancy

Cetirizine and loratadine are the safest first-line antihistamines for pregnant women across all trimesters, with the most extensive safety data demonstrating no increased risk of congenital malformations. 1

First-Line Antihistamine Recommendations

The preferred antihistamines during pregnancy are:

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

A 2017 meta-analysis of 37 studies confirmed that H1 antihistamines overall show no increased risk of major malformations (OR 1.07; 95% CI 0.98-1.16), spontaneous abortions, prematurity, stillbirth, or low birth weight 2

Alternative First-Generation Options

If second-generation antihistamines are unavailable:

• Chlorpheniramine has been specifically recommended as a first-choice agent with sufficient human observational data demonstrating no significant increase in congenital malformations when used during the first trimester 3
• The main drawback is sedative qualities and possible effect on performance, though this does not affect its safety profile 3
• Chlorpheniramine is often chosen by U.K. clinicians because of its long safety record 3, 4

Critical Timing Considerations

The first trimester (organogenesis period) is the most critical window for potential medication-related congenital malformations 1

However, the accumulated evidence shows second-generation antihistamines (cetirizine, loratadine) have excellent safety records even with first trimester exposure 1

Medications to Strictly Avoid

Hydroxyzine is the only antihistamine specifically contraindicated during early pregnancy:

• Explicitly contraindicated based on animal data showing it induced fetal abnormalities in rats and mice at doses substantially above the human therapeutic range 3
• Both British and U.S. guidelines list hydroxyzine among medications to avoid during pregnancy, particularly in the first trimester 3
• Cetirizine, the active metabolite of hydroxyzine, is recommended as the safer alternative 3

Other antihistamines to avoid:

• Levocetirizine should be avoided during the first trimester due to limited safety data specifically for this medication 4
• Desloratadine, azelastine, and fexofenadine have limited human pregnancy data and should be avoided when better-studied alternatives exist 1

Medications to Avoid Combining with Antihistamines

Oral decongestants (phenylephrine, pseudoephedrine) should be avoided during the first trimester:

• Associated with conflicting reports of gastroschisis and small intestinal atresia 3, 4, 1
• The risk of malformations increases when decongestants are combined with acetaminophen or salicylates 3, 1

Practical Treatment Algorithm

For any trimester requiring antihistamine therapy:

1. Start with cetirizine or loratadine as first-line antihistamine therapy 1
2. Use the lowest effective dose for the shortest possible time to minimize exposure 3
3. Adjust dosing for renal impairment: cetirizine dose should be halved in moderate renal impairment and avoided in severe renal impairment (creatinine clearance < 10 mL/min); loratadine should be used with caution in severe renal impairment 3

Consider non-antihistamine alternatives first:

• Intranasal corticosteroids (budesonide preferred) are actually the safest and most effective first-line treatment for rhinitis during pregnancy, with minimal systemic absorption 1
• Sodium cromolyn nasal spray is considered safe (Pregnancy Category B) but requires frequent four-times-daily dosing 4, 1

Common Pitfalls to Avoid

• Do not assume all antihistamines have equivalent safety profiles—the quality of human pregnancy data varies dramatically 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 1
• Do not combine oral decongestants with acetaminophen or NSAIDs during pregnancy, as this increases malformation risk 1
• Do not overlook that the FDA drug label for cetirizine states "if pregnant: ask a health professional before use" 5, though extensive guideline evidence supports its safety as a first-line choice