Antihistamine Use During Pregnancy
If antihistamine therapy is necessary during pregnancy, use cetirizine or loratadine as first-line agents, particularly after the first trimester; if treatment is needed during the first trimester, chlorphenamine is preferred due to its long safety record. 1
General Safety Principles
While it is best to avoid all antihistamines during pregnancy, especially during the first trimester, none has been shown to be teratogenic in humans. 1 The first trimester represents the highest risk period for potential congenital malformations due to organogenesis. 2
Recommended Antihistamines by Safety Profile
Preferred Options
Cetirizine and loratadine are classified as FDA Pregnancy Category B drugs, indicating no evidence of harm to the fetus during pregnancy, though well-controlled human studies are not available. 1, 2
Chlorphenamine (chlorpheniramine) is often chosen by UK clinicians when antihistamine therapy is necessary because of its long safety record. 1, 2
Second-generation antihistamines (cetirizine and loratadine) are the antihistamines of choice during pregnancy based on their safety profiles. 3
Antihistamines to Avoid
Hydroxyzine is specifically contraindicated during early pregnancy based on animal data showing potential risks and is the only antihistamine with a specific contraindication in UK manufacturer guidelines. 1, 2
First-generation antihistamines should generally be avoided due to their sedative and anticholinergic properties, though chlorphenamine is an exception given its extensive safety data. 1
Diphenhydramine should be used cautiously despite being commonly used by pregnant patients, as there remains concern over a case-control study suggesting an association with cleft palate that has not been sufficiently refuted. 1
Levocetirizine should be avoided during the first trimester if possible due to limited safety data specifically for this medication. 2
Treatment Algorithm by Trimester
First Trimester (Highest Risk Period)
Prioritize non-pharmacological approaches first. 2
If antihistamine treatment is essential, choose chlorphenamine due to its long safety record. 1, 2
Alternatively, cetirizine or loratadine may be used as they have FDA Pregnancy Category B classification and more accumulated safety data than newer agents. 2
Avoid hydroxyzine, levocetirizine, and intranasal antihistamines entirely. 2, 3
Second and Third Trimesters
Cetirizine and loratadine are preferred second-generation antihistamines. 1, 3
Continue to avoid hydroxyzine throughout pregnancy. 1
Important Caveats and Pitfalls
Do not assume all antihistamines have equivalent safety profiles during pregnancy—they do not, and specific agents carry different risk levels. 2
Avoidance or caution is recommended for most antihistamines, particularly in the first trimester and during lactation. 1
Benefit-risk assessment is crucial: the potential benefit of symptom relief must be weighed against potential risks to the fetus. 2
Oral decongestants should not be combined with antihistamines during the first trimester, as combining decongestants with other medications may increase the risk of malformations such as gastroschisis. 1
Large-scale studies show approximately 13% of pregnant women use antihistamines during early pregnancy, with analyses of over 41,000 pregnancies showing lack of strong evidence to conclude that birth defects are associated with antihistamine exposure. 4
Alternative and Adjunctive Therapies
Sodium cromolyn nasal spray is considered safe during pregnancy (Pregnancy Category B) due to its topical application and reassuring safety data, though it requires frequent four-times-daily dosing. 1
Intranasal corticosteroids may be used for nasal symptoms with a favorable safety profile based on low systemic exposure. 1, 2
Topical treatments should be considered as a first approach before systemic antihistamines. 5