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

Safe Antihistamines in Pregnancy

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

Recommended First-Line Agents

Both cetirizine and loratadine carry FDA Pregnancy Category B classification and should be your default choices when antihistamine therapy is necessary. 1, 2 These second-generation agents now have accumulated safety data comparable to older first-generation antihistamines but without the problematic sedative effects that impair maternal performance and quality of life. 3, 1

• Cetirizine has the most robust safety evidence, particularly for third trimester use, and is specifically recommended by the American Academy of Allergy, Asthma, and Immunology. 1, 4
• Loratadine has been studied in over 2,000 pregnant women with no demonstrated increase in major congenital malformations. 5, 4

Critical Timing Considerations

The first trimester (organogenesis period) is the most critical window for potential medication-related congenital malformations. 3, 1, 2 However, the accumulated evidence shows that cetirizine and loratadine maintain excellent safety records even with first trimester exposure. 3, 1

Medications to Specifically Avoid

• Hydroxyzine is contraindicated during early pregnancy based on animal teratogenicity data. 3, 1, 2
• Levocetirizine, desloratadine, azelastine, and fexofenadine have limited human pregnancy data and should be avoided when better-studied alternatives (cetirizine, loratadine) exist. 3, 1, 6
• Oral decongestants (phenylephrine, pseudoephedrine) must be avoided during the first trimester due to associations with gastroschisis and small intestinal atresia, with risk further increased when combined with acetaminophen or NSAIDs. 3, 1, 2

Optimal Treatment Algorithm

1. Start with intranasal corticosteroids (budesonide preferred) as first-line therapy for rhinitis symptoms—these are actually safer and more effective than antihistamines with minimal systemic absorption. 1, 5, 4

2. Add cetirizine or loratadine if additional symptom control is needed beyond intranasal corticosteroids. 1, 2

3. Consider sodium cromolyn nasal spray (Pregnancy Category B) if the patient refuses corticosteroids, though efficacy is lower and requires inconvenient four-times-daily dosing. 3, 1

4. Reserve montelukast (Pregnancy Category B) only for patients with documented excellent pre-pregnancy response to this agent. 3, 1

Alternative Safe Options

While first-generation antihistamines like chlorpheniramine have long safety records with over 200,000 first trimester exposures showing no increased teratogenic risk, their sedative effects make them less desirable than cetirizine or loratadine. 3, 5, 7 The notion that older antihistamines are automatically safer is outdated—second-generation agents now have comparable safety data without the quality-of-life impairment from sedation. 3, 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 between agents. 1, 2
• Do not reflexively choose first-generation antihistamines based solely on "longer history of use"—cetirizine and loratadine now have comparable safety data without sedation risks. 3, 1
• Do not overlook intranasal corticosteroids, which are often more effective than antihistamines and have excellent safety profiles during pregnancy. 1, 5
• Do not combine oral decongestants with acetaminophen or NSAIDs during pregnancy, as this combination increases malformation risk. 3, 1