Is desloratadine (antihistamine) safe to use during pregnancy?

Desloratadine Safety in Pregnancy

Desloratadine can be used during pregnancy with reassuring safety data, though cetirizine and loratadine are preferred as first-line second-generation antihistamines due to more extensive safety documentation, particularly during the first trimester. 1, 2

Evidence-Based Recommendation Framework

First-Line Antihistamine Choices During Pregnancy

For second-generation antihistamines, cetirizine and loratadine should be selected first because they have been confirmed safe through large birth registries, case-control studies, and cohort studies, with more accumulated safety data than desloratadine. 1, 2

• Chlorpheniramine (first-generation) remains the gold standard with the longest safety record and sufficient human observational data demonstrating no significant increase in congenital malformations during first trimester exposure, though it causes sedation. 2

• The FDA label for desloratadine classifies it as Pregnancy Category C, stating "there are no adequate and well-controlled studies in pregnant women" and that it "should be used during pregnancy only if clearly needed." 3

Desloratadine-Specific Safety Data

The most recent and highest quality study demonstrates that desloratadine does not increase risk of adverse fetal outcomes. A 2020 Danish nationwide cohort study of 1,287,668 pregnancies found no statistically significant increased risk when comparing desloratadine to loratadine for: 4

• Major birth defects (prevalence OR 1.07,95% CI 0.77-1.50) 4

• Spontaneous abortion (HR 1.15,95% CI 0.96-1.37) 4

• Preterm birth (prevalence OR 0.84,95% CI 0.67-1.05) 4

• Small for gestational age (prevalence OR 0.97,95% CI 0.80-1.16) 4

• Stillbirth (HR 0.91,95% CI 0.31-2.70) 4

• This study concluded that desloratadine's fetal safety profile is similar to currently recommended second-generation antihistamines during pregnancy. 4

Clinical Reasoning for Antihistamine Selection

Since desloratadine is the principal metabolite of loratadine, it can be assumed that a similar safety profile applies, though direct human studies were limited until the 2020 Danish cohort study provided robust evidence. 5

The hierarchy of antihistamine selection during pregnancy should be:

1. First choice: Chlorpheniramine (longest safety record, most extensive data) 2
2. Second choice: Cetirizine or loratadine (less sedating, confirmed safe, extensive registry data) 1, 2
3. Acceptable alternative: Desloratadine (reassuring 2020 cohort data, similar profile to loratadine) 4
4. Avoid completely: Hydroxyzine (specifically contraindicated based on animal data showing fetal abnormalities) 2

First Trimester Considerations

The first trimester is the most critical period for concern about medication-induced congenital malformations due to organogenesis. 1, 2

• While guidelines recommend avoiding levocetirizine during the first trimester due to limited safety data, desloratadine now has more robust evidence from the 2020 nationwide study. 1, 4

• If antihistamine treatment is necessary during the first trimester, cetirizine and loratadine remain preferred due to their FDA Pregnancy Category B classification and more extensive accumulated safety data. 1

Critical Safety Warnings

Never combine any antihistamine with oral decongestants during the first trimester. Phenylephrine and pseudoephedrine have conflicting reports of association with gastroschisis and small intestinal atresia. 1, 6

• The risk of malformations increases further when decongestants are combined with acetaminophen or salicylates. 1, 6

Alternative Non-Antihistamine Options

If antihistamines are insufficient or additional therapy is needed: 1

• Intranasal corticosteroids (particularly budesonide) have a favorable safety profile during pregnancy with moderate to high strength of evidence. 1, 7
• Sodium cromolyn nasal spray is considered safe (FDA Pregnancy Category B), though requires frequent dosing. 1

Practical Algorithm for Desloratadine Use

If a pregnant patient is already taking desloratadine:

• Continue use with reassurance based on the 2020 Danish cohort data showing no increased risk. 4
• No need to switch medications if symptoms are well-controlled. 4

If initiating new antihistamine therapy:

• Start with cetirizine or loratadine as first-line second-generation options. 1, 2
• Consider chlorpheniramine if sedation is acceptable and patient prefers the most extensively studied option. 2
• Desloratadine is an acceptable alternative if other second-generation antihistamines are ineffective or not tolerated. 4

Breastfeeding Considerations

Desloratadine passes into breast milk, requiring a decision between discontinuing nursing or discontinuing the medication, weighing benefit to the mother against possible risk to the child. 3