Are antihistamines contraindicated during pregnancy?

Are Antihistamines Contraindicated in Pregnancy?

No, antihistamines are not contraindicated in pregnancy—with the critical exception of hydroxyzine, which is specifically contraindicated during early pregnancy. Most antihistamines have excellent safety records and can be used throughout pregnancy when clinically indicated. 1, 2

Recommended First-Line Antihistamines

The safest antihistamines during pregnancy are cetirizine and loratadine, which should be your first-choice agents. 3

• Cetirizine has the most robust safety evidence with no increased risk of congenital malformations across all trimesters, including first trimester exposure when organogenesis occurs 3
• Loratadine carries FDA Pregnancy Category B status with extensive human observational data confirming safety across all trimesters 3
• Both medications have accumulated safety data from large birth registries, case-control studies, and cohort studies demonstrating no significant increase in birth defects 2
• These second-generation antihistamines offer the advantage of less sedation compared to first-generation agents, improving maternal quality of life 2

Alternative Safe Options

Chlorpheniramine (a first-generation antihistamine) is also safe and has been specifically recommended as a first-choice agent due to its longevity of use and excellent safety record. 2

• Chlorpheniramine has sufficient human observational data demonstrating no significant increase in congenital malformations when used during the first trimester 2
• The main drawback is sedation and possible impairment of maternal performance, though this does not affect its safety profile 2
• First-generation antihistamines as a class have not been linked to increased risk of congenital anomalies, with meta-analyses examining 200,000 first trimester exposures showing no increased teratogenic risk 1, 4

The One Contraindicated Antihistamine

Hydroxyzine is the only antihistamine specifically contraindicated during early pregnancy. 2

• Animal studies showed hydroxyzine induced fetal abnormalities in rats and mice at doses substantially above the human therapeutic range 2
• Neonatal withdrawal syndrome has been documented with hydroxyzine use later in pregnancy, with signs including tremors, irritability, and hyperactivity lasting up to 5 weeks 2
• Use cetirizine instead—it is the active metabolite of hydroxyzine and has a long safety record with no significant increase in congenital malformations 2

Critical Timing Considerations

The first trimester is the most critical period for medication-related congenital malformations due to organogenesis, yet the recommended antihistamines maintain excellent safety records even during this vulnerable window. 2, 3

• While caution is advised throughout pregnancy, accumulated evidence shows cetirizine, loratadine, and chlorpheniramine have excellent safety records with first trimester exposure 2, 3
• Antihistamine use during the last 2 weeks of pregnancy was associated with retrolental fibroplasia in premature infants in one study, though these findings have not been corroborated 1

Antihistamines with Limited Data (Use Alternatives Instead)

Levocetirizine, desloratadine, azelastine, and fexofenadine have limited human pregnancy data and should be avoided when better-studied alternatives exist. 3

• The American Academy of Allergy, Asthma, and Immunology recommends avoiding levocetirizine during the first trimester due to limited safety data 5
• No controlled trials exist for fexofenadine in human pregnancy 6

Important Medication Combinations to Avoid

Never combine antihistamines with oral decongestants during the first trimester. 2

• Oral decongestants (phenylephrine, pseudoephedrine) have conflicting reports of association with gastroschisis and small intestinal atresia 2, 3
• The risk of malformations increases when decongestants are combined with acetaminophen or salicylates 2, 3

Practical Treatment Algorithm

For pregnant women requiring antihistamine therapy:

1. First-line choice: Cetirizine or loratadine throughout all trimesters 3
2. Alternative first-line: Chlorpheniramine if sedation is acceptable 2
3. Dose optimization: Use the lowest effective dose for the shortest possible time 2
4. Renal adjustment: Halve cetirizine dose in moderate renal impairment; avoid in severe renal impairment (creatinine clearance <10 mL/min); use loratadine with caution in severe renal impairment 2
5. Consider intranasal corticosteroids (particularly budesonide) as first-line therapy for rhinitis symptoms, as they are actually safer and more effective than antihistamines with minimal systemic absorption 3

Common Pitfalls to Avoid

• Do not assume all antihistamines have equivalent safety profiles—they do not, and hydroxyzine is specifically contraindicated 2, 3
• Do not reflexively choose first-generation antihistamines based solely on "longer history of use"—second-generation agents (cetirizine, loratadine) now have comparable safety data without sedation risks 3
• Do not overlook that antihistamines may theoretically reduce milk production during breastfeeding, though this is not well-established 1