Chlorpheniramine Safety in Pregnancy
Chlorpheniramine is safe to use during pregnancy, including the first trimester, and is recommended as a first-choice antihistamine due to its excellent safety record and observed lack of congenital malformations. 1, 2
Safety Profile and Evidence Base
Chlorpheniramine has been 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, 2
The first trimester is the most critical period for concern about medication-induced congenital malformations due to organogenesis, yet chlorpheniramine has maintained an excellent safety record even during this vulnerable period. 1
Both first-generation antihistamines (like chlorpheniramine) and second-generation antihistamines generally have excellent safety records and do not show a significant increase in congenital malformations when used during the first trimester. 1
Practical Considerations
The main drawback of chlorpheniramine is its sedative qualities and possible effect on performance, which may make it less desirable than second-generation antihistamines from a quality of life perspective, though this does not affect its safety profile. 1
Use the lowest effective dose (4-12 mg in adults) for the shortest possible time to minimize exposure while maintaining symptom control. 2
Chlorpheniramine is commonly chosen by clinicians specifically because of its long safety record when antihistamine treatment is necessary during pregnancy. 3
Alternative Options
Second-generation antihistamines such as cetirizine and loratadine are now also confirmed safe through large birth registries, case-control studies, and cohort studies, and offer the advantage of less sedation. 1, 2
These alternatives may be preferred if sedation is a concern for the patient's daily functioning, though chlorpheniramine remains a validated first-line choice. 2
Important Caveats
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, 3
The risk of malformations increases when decongestants are combined with acetaminophen or salicylates. 1, 3
While the American College of Obstetricians and Gynecologists suggests avoiding all antihistamines when possible during pregnancy, none has been shown to be teratogenic in humans, and chlorpheniramine specifically has the strongest safety data. 2