What antihistamine (anti-allergic medication) is safe to use during pregnancy?

Safe Antihistamines in Pregnancy

Chlorpheniramine, cetirizine, and loratadine are the safest antihistamines to use during pregnancy, including the first trimester, with chlorpheniramine having the longest safety record but cetirizine and loratadine offering the advantage of less sedation. 1

First-Line Antihistamine Options

Chlorpheniramine (First-Generation)

• Chlorpheniramine is specifically recommended as a first-choice agent during pregnancy because of its observed safety and longevity of use, with sufficient human observational data demonstrating no significant increase in congenital malformations when used during the first trimester 1
• Clinicians in the U.K. often choose chlorpheniramine when antihistamine therapy is necessary because of its long safety record 2
• The main drawback is its sedative qualities and possible effect on performance, which may make it less desirable from a quality of life perspective, though this does not affect its safety profile 1
• Standard dosing is 4-12 mg, with the recommendation to use the lowest effective dose for the shortest possible time to minimize exposure 1

Cetirizine (Second-Generation)

• Cetirizine is classified as FDA Pregnancy Category B, indicating no evidence of harm to the fetus during pregnancy 2, 3
• Large birth registries, case-control studies, and cohort studies have confirmed cetirizine's safety and it offers the advantage of less sedation compared to first-generation antihistamines 1
• A safety database study of 228 pregnancies with maternal cetirizine exposure found that 83.7% resulted in live births, with only 2 congenital malformations reported in 41 live births, suggesting no increase in adverse outcomes above background rates 4
• Meta-analysis examining 200,000 first trimester exposures to antihistamines failed to show increased teratogenic risk 5

Loratadine (Second-Generation)

• Loratadine is also classified as FDA Pregnancy Category B and is the most studied second-generation antihistamine with a total patient cohort of 2,147 women exposed, showing no increased risk of major congenital malformations 2, 5
• Loratadine has been confirmed safe through large birth registries, case-control studies, and cohort studies 1

Antihistamines to Avoid

Hydroxyzine

• Hydroxyzine is the only antihistamine specifically contraindicated during the early stages of pregnancy based on animal data showing potential risks 2, 3

Levocetirizine

• Levocetirizine should be avoided during the first trimester if possible due to limited safety data specifically for this medication 3
• While it is the principal metabolite of loratadine, there are no direct human studies to confirm its safety profile 5

Critical Caveats and Pitfalls

Combination Products

• Avoid combining chlorpheniramine with oral decongestants during the first trimester, as oral decongestants (phenylephrine, pseudoephedrine) have conflicting reports of association with congenital malformations such as gastroschisis and small intestinal atresia 1
• The risk of malformations increases when decongestants are combined with acetaminophen or salicylates 1

Renal and Hepatic Impairment

• The dose of cetirizine 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

Practical Treatment Algorithm

For pregnant women requiring antihistamine therapy:

1. First trimester (most critical period for organogenesis):

   • Choose chlorpheniramine if sedation is acceptable 1
   • Choose cetirizine or loratadine if non-sedating antihistamine is preferred 1
   • Avoid all combination products with decongestants 1

2. Second and third trimesters:

   • Same options as first trimester remain safe 1
   • All three agents (chlorpheniramine, cetirizine, loratadine) have excellent safety records throughout pregnancy 1

3. Dose optimization:

   • Use the lowest effective dose for the shortest possible time 1
   • Adjust for renal impairment if present 2