Safety of antihistamines during pregnancy and lactation

First-generation antihistamines

Antihistamines targeting histamine–type 1 (H₁) receptors are commonly used to treat allergic rhinitis. Examples of first-generation antihistamines are brompheniramine, chlorpheniramine, dimenhydrinate, diphenhydramine, doxylamine, hydroxyzine, and pheniramine. Most—with the exception of doxylamine and dimenhydrinate, both used for the treatment of nausea and vomiting, and hydroxyzine (prescription-only)—are commonly found in over-the-counter allergy and cold medications. None of the medications in this class of drugs has been reported to increase fetal risk when used at any time during pregnancy.2 Epidemiologic data support safety in early pregnancy,3 with a meta-analysis involving more than 200 000 participants concluding that there was no increase in any type of congenital malformation.4

Second-generation antihistamines

At present, medications from this class of drugs are preferred because they do not cause central nervous system adverse effects (eg, drowsiness) and because they are available without prescription. Examples of second-generation antihistamines are cetirizine, desloratadine, fexofenadine, and loratadine.

Antihistamines and breastfeeding

Although the data regarding the use of first-generation antihistamines and breastfeeding is limited, only minimal amounts of these drugs have been reported to be secreted in breast milk.16,17 In a telephone follow-up study conducted by Motherisk, 10% of mothers reported irritability and colicky symptoms in their infants exposed to various antihistamines, and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention.18 Therefore, short-term or occasional use of the older generation antihistamines would not be expected to be a concern during breastfeeding.

Among the second-generation H₁ blockers, data on drug concentration in breast milk are available for loratadine, desloratadine, and fexofenadine. The pharmacokinetics of loratadine and its metabolite desloratadine in breast milk were studied in 6 lactating women after a single oral dose of 40 mg of loratadine,19 which is 4 times the current standard therapeutic dose. Assuming the breast milk intake by an infant is 150 mL/kg daily, the maximum infant loratadine-equivalent dose based on the highest concentration of loratadine and desloratadine in breast milk was estimated to be 7.3 μg/kg daily (ie, 1.1% of the daily dose given to the mother in mg/kg). The pharmacokinetics of fexofenadine in breast milk were studied in 4 lactating women taking 60 mg of terfenadine every 12 hours.20 The maximum infant dose of fexofenadine based on the highest concentration of fexofenadine in breast milk would be 9 μg/kg daily (ie, 0.45% of the daily dose given to the mother in mg/kg). Considering the minimal exposure of a nursing infant to the drugs through breast milk, maternal use of loratadine, desloratadine, or fexofenadine in a standard therapeutic dose is unlikely to result in adverse effects in nursing infants and is considered to be compatible with breastfeeding.

Conclusion

Although seasonal allergy is not a life-threatening medical condition, it can be extremely troublesome for pregnant women and breastfeeding mothers. Based on the current body of evidence, which is large, first-generation H₁ blockers are not associated with an increased risk of major malformations or any other adverse fetal effects. Although there is less evidence on second-generation H₁ blockers, they have also not been associated with an increased risk of adverse pregnancy outcomes. In addition, none of the antihistamines is excreted in the breast milk in an appreciable amount so as to have any adverse effects on the breastfeeding infant. Therefore, pregnant and breastfeeding women can be reassured that they can alleviate their symptoms without posing an increased risk to their fetuses or infants.